Relationship between Angiotensin II, Vascular Endothelial Growth Factor, and Arteriosclerosis Obliterans

Liu, Yulian; Cui, Yuzhi; Zhou, Zongqi; Liu, Bin; Liu, Zheng; Li, Gang

doi:https://doi.org/10.1155/2023/1316821

Disease Markers

On this page

Abstract Introduction Methods Results Discussion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Special Issue

Microvessel Structure and Microvascular Alterations in Chronic Diseases 2022

View this Special Issue

Research Article | Open Access

Volume 2023 | Article ID 1316821 | https://doi.org/10.1155/2023/1316821

Relationship between Angiotensin II, Vascular Endothelial Growth Factor, and Arteriosclerosis Obliterans

Yulian Liu,¹Yuzhi Cui,¹Zongqi Zhou,¹Bin Liu,²Zheng Liu,³and Gang Li²

Academic Editor: Yi Shao

Received18 Sept 2022

Revised11 Nov 2022

Accepted24 Nov 2022

Published21 Feb 2023

Abstract

Objective. To investigate the relationship between angiotensin II (Ang II), vascular endothelial growth factor (VEGF), and arteriosclerosis obliterans (ASO). Methods. 60 ASO patients diagnosed and treated from October 2019 to December 2021 were selected for the observation group while 30 healthy physical examiners were for the control group. The general information (gender, age, history of smoking, diabetes, and hypertension) and arterial blood pressure (systolic and diastolic blood pressure) of the two groups were collected, and parameters like disease site and duration, Fontaine stage, and ankle-brachial index (ABI) of ASO patients have been evaluated. Ang II, VEGF, uric acid (UA), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC) were also detected for the two groups. The variations in UA, LDL, HDL, TG, and TC among two groups along with levels of Ang II and VEGF in ASO patients in accordance to conditions like the general situation, disease duration, disease site, Fontaine stage, and ABI risk level have been studied to establish a correlation between Ang II and VEGF and ASO. Results. (1) The proportion of males with a history of smoking, diabetes, and hypertension was higher () among ASO patients in comparison to the control group. The diastolic blood pressure, LDL, TC, Ang II, and VEGF levels were found to be higher () whereas HDL was low (). (2) The level of Ang II in male patients with ASO was significantly higher than that in female ASO patients (). In ASO patients, the levels of Ang II and VEGF increased not only with age () but also with progression in Fontaine stages II, III, and IV (). (3) Logistic regression analysis revealed Ang II and VEGF as risk factors for ASO. (4) An AUC (area under the ROC (receiver operator characteristic) curve) for Ang II and VEGF for the diagnosis of ASO was 0.764 (good) and 0.854 (very good), respectively, while their combined AUC in diagnosing ASO was 0.901 (excellent). The AUC of Ang II and VEGF together in diagnosing ASO was greater than that of Ang II and VEGF alone along with higher specificity as well (all ). Conclusion. Ang II and VEGF were correlated with the occurrence and development of ASO. The AUC analysis demonstrates that Ang II and VEGF were highly discriminative of ASO.

1. Introduction

Arteriosclerosis obliterans (ASO) is a common peripheral arterial occlusive disease. It is manifested in systemic arteriosclerosis in the arteries of the lower limbs. In the early stages, the clinical manifestations involve limb cooling, fear of cold, numbness, intermittent claudication, etc. In the later stages, ulceration and gangrene may occur with amputation occurrence in serious cases [1]. ASO has been reported to involve more middle-aged and elderly people (over 45 years old) also with more males than females [2]. It is also reported that the incidence rate of ASO is as high as 15% ~20%, and the annual mortality is 4% ~6% [3]. As China’s population ages, the incidence rate of ASO is increasing year by year affecting both physical and mental health as well as patient quality of life [4]. Atherosclerosis (AS) is the pathological basis of ASO [5] where the pathogenesis of AS is complex and there are many theories about it. Among them, the theory of chronic inflammation had played a crucial role in studying AS pathogenesis and also received widespread attention in the medical community [6, 7].

In 1997, researchers first found that Ang II can induce endothelial cells to produce adhesion molecules, which are closely related to inflammation. With the deepening of research, a new idea has been proposed that Ang II can cause inflammation and participate in the pathogenesis of AS [8].

Angiotensin II (Ang II) can induce the aggregation of a variety of inflammatory cytokines, lead to the proliferation of the middle layer of the artery, and promote inflammatory infiltration in the surrounding area of the middle layer of the artery, thus accelerating the development of AS. Its advantages in evaluation are increasingly prominent [9]. In addition, the abnormal proliferation of vascular smooth muscle cells (VSMCs) also plays an important role in the development of AS. As a critical functional factor of the renin-angiotensin-aldosterone system (RAAS), Ang II can act on VSMCs through autocrine and paracrine pathways, thus stimulating the abnormal proliferation of VSMCs [10] and stimulating angiogenesis in lower concentrations but inhibits in higher concentrations [11]. The process of angiogenesis involves the differentiation, proliferation, and migration of endothelial cells (ECs) and results in tubulogenesis and formation of vessels [12]. Ang II promotes EC proliferation and angiogenesis through the angiotensin type 1 receptor (AT1R) [13, 14]. Buharaliogl et al. found that Ang II-induced angiogenesis was phosphorylated by splenic tyrosine-mediated kinase through VEGF receptor-1.

Vascular endothelial growth factor (VEGF) is a highly specific mitogen of vascular endothelial cells [15] that can induce endothelial cell proliferation, increase vascular permeability, and promote inflammatory response [16]. Studies have found that once neovascularization occurs in AS plaques, the expression of VEGF and its receptor in AS plaques will increase, so it is inferred that there is a close association between VEGF expression and the development of AS plaques [17–20]. Simultaneously, studies have also confirmed [21] that VEGF has strong expression in smooth muscle and macrophages of atherosclerotic plaques. VEGF plays a crucial role in the formation of AS, which may be due to the fact that although VEGF can promote angiogenesis; these new blood vessels are often immature and prone to rupture, leading to thrombosis, and in-cooperated with highly expressed fibrinogen (FIB) to accelerate the formation and development of AS [22]. Meanwhile, studies have found that VEGF and its receptor are critically linked to the abnormal proliferation of VSMCs [23]. This study intends to explore the characteristics variations of Ang II and VEGF levels in ASO patients for preliminarily exploring the relationship between Ang II, VEGF, and ASO.

2. Material

Main experimental reagent and software product information.

3. Methods

3.1. Study Subjects

The subjects in the observation group were all ASO patients hospitalized in the peripheral vascular department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from October 2019 to December 2021. The control groups were all from the health checkers in the physical examination center of the Affiliated Hospital at Shandong University of Traditional Chinese Medicine. This study was approved by the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine ((2022) Lunlun-Review No. (108) -KY). The following data have been utilized as diagnostic criteria: ASO western medical diagnostic criteria [24] with (1) years old; (2) history of smoking, diabetes, hypertension, hyperlipidemia, and other high-risk factors; (3) clinical manifestations of ASO in lower limbs; (4) arterial pulsation in the distal end of the ischemic limb weakened or disappeared; and (5) ; (6) color doppler ultrasound, CTA, MRA, DSA, and other imaging examinations showed stenosis or occlusion of the corresponding arteries. A clinical diagnosis of ASO can be made by meeting the following 4 diagnostic criteria: Fontaine staging standard [25] stage I: asymptomatic, stage II: intermittent claudication, stage III: resting pain, and stage IV: tissue ulcer and gangrene. The following case inclusion criteria were utilized: (1) those who met the diagnostic criteria of ASO, (2) , and (3) those who have signed the informed consent form. The following were case exclusion criteria: (1) those who have suffered from serious cardiovascular and cerebrovascular diseases in the past 3 months; (2) accompanied by serious infectious diseases, malignant tumors, and autoimmune diseases; (3) pregnant and lactating women; (4) those who have a mental illness or are unable to cooperate; and (5) incomplete data affecting judgment.

3.2. Study Subjects and Grouping

A total of sixty ASO patients who met the natriuretic excretion criteria were set as an observation group while 30 healthy physical examiners during the same period acted as a control group.

3.3. Clinical and Laboratory Variables

This represents the general data where the following clinical indicators were used: (1) gender, (2) age, (3) disease duration, (4) the site of the disease, (5) Fontaine staging, (6) smoking history, (7) history of diabetes, and (8) history of hypertension. The following parameters were utilized as laboratory variables for the detection of AS like (1) blood pressure: systolic blood pressure and diastolic blood pressure, (2) angiotensin II (Ang II), (3) vascular endothelial growth factor (VEGF), (4) ankle-brachial index (ABI), and (5) biochemical indicators: low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), total cholesterol (TC), and uric acid (UA).

3.4. Study Procedures

The following study procedures were utilized for this study that involves (1) measurement method of blood pressure: the subject rested calmly for 5 min before receiving the examination, took a sitting or lying position, used a mercury sphygmomanometer to measure three times, and calculated the average value of three times of blood pressure. The blood pressure of both arms was measured while the higher one was taken as the final blood pressure. (2) Measurement method of ABI: Nicolet vasoguard + channel blood vessel tester was used, and special personnel was assigned to detect it. The ABI of both sides was detected, and the lower was taken as the final value. (3) 3 ml of peripheral venous blood in fasting decubitus position was taken into a centrifuge after standing for 1 h at normal temperature, plasma was taken after centrifugation, and it was stored at -70°C for Ang II detection. Plasma Ang II was determined by radioimmunoassay. (4) 5 ml of fasting peripheral venous blood was taken and placed in the coagulation-promoting tube, centrifuged at 4000 r/min for 5 min, the upper serum was taken for examination, and serum VEGF was measured with enzyme-linked immunosorbent assay. (5) 2 ml of fasting peripheral venous blood was taken, and LDL, HDL, TG, TC, and UA were detected by AU5800 automatic biochemical analyzer (model: 5821, no. DSH-001).

3.5. Statistical Analysis

The statistical software IBM SPSS28.0 has been utilized for data processing. All measured data were expressed as (). -test was used for the comparison of data conforming to normal distribution and homogeneity of variance, and analysis of variance was used for the comparison among multiple groups. Nonparametric test was used for data not conforming to normal distribution. The count data were expressed by frequency and composition ratio ( (%)). We have utilized the test, a binary logistic regression model for correlation analysis; the ROC curves for the diagnostic value of the detection index and the AUC of ROC is compared by Medcalc software. The values () were statistically considerable.

4. Results

4.1. Subject Demographics and Study Variables

In the 60 cases in the observation group, around 42 were males, and 18 females with an average age of years were found. The shortest disease period was of 1 year while the longest of 28 years with an average duration of years. There were 13 cases located in the left lower limb, 26 in the right lower limb, and 21 in both lower limbs. According to the Fontaine stage, there were 14, 7, and 39 cases in stages II, III, and IV, respectively. Of the 30 cases in the control group, there were 11 males and 19 females with an average age of years.

As compared to the control group, a higher proportion of males with a history of smoking as well as diabetes were found in the observation group and also the levels of diastolic blood pressure, TC, Ang II (Figure 1), and VEGF (Figure 2) were higher while the HDL level was lower. These variations among the two groups were statistically considerable with values (). In comparison to the control group, the proportion of hypertension history and LDL level in the observation group was higher; also, these differences between the two groups were statistically considerable with values (). We have not found any statistically considerable differences in age, systolic blood pressure, TG, and UA between the two groups () (Table 1).

4.2. Comparisons within Stratified Subgroups of Cases

A total of sixty ASO patients were stratified according to gender, age, duration, and site of disease, diabetes and hypertension history, Fontaine stage, and ABI risk grade; and the changes in Ang II and VEGF levels were observed. We have found the following results for Ang II and VEGF comparison with different parameters.

4.3. Comparison of Ang II and VEGF Levels between Different Genders of ASO Patients

The level of Ang II was found higher in males than females for 60 cases of ASO, and the difference between the two groups was statistically significant (, ). The VEGF level was also found higher in males than females but without any statistically considerable difference between the two groups (, ) (Table 2 and Figures 3 and 4).

4.4. Comparison of Ang II and VEGF Levels in ASO Patients at Different Ages

60 patients with ASO were divided into groups according to the age interval of 10 years. There were 3 patients aged 41 to 50 years, 23 patients aged 51 to 60 years, 31 patients aged 61 to 70 years, and 3 patients aged 71 to 80 years. We have found that, with an increase in age, the levels of Ang II and VEGF also increased in ASO patients, and the difference was statistically significant as analyzed by the Kruskal-Wallis test (). Further, the level of Ang II in the 61-70 years old age group was significantly higher than that in the 41-50 years old group (), and there was not any statistically considerable difference between the other two groups (). Also, the VEGF level in the 71-80 years old group was found higher than that of the 41-50 years old group () while there was not any statistically considerable difference between the other two groups () (Table 3 and Figures 5 and 6).

4.5. Comparison of Ang II as well as VEGF Levels among Patients with ASO at Different Sites

Sixty patients with ASO were divided into three groups according to the different disease sites including 13, 26, and 21 cases at the left lower limb, right lower limb, and both lower limbs, respectively. Kruskal-Wallis test showed that there was not any statistically considerable difference for Ang II as well as VEGF levels among these groups () (Table 4 and Figures 7 and 8).

4.6. Comparison of Ang II as well as VEGF Levels among ASO Patients with Different Disease Durations

We grouped 60 patients with ASO according to the disease duration [26], where 29 patients had a duration of , 4 cases with , 18 cases with , and 9 cases with disease . The Kruskal-Wallis test showed that there was not any statistically considerable difference for Ang II as well as VEGF levels among these groups () (Table 5 and Figures 9 and 10).

4.7. Comparison of Ang II as well as VEGF Levels among Patients of ASO with or without a Smoking History

The level of Ang II in ASO patients with smoking history was higher than that in patients without smoking history, and there was not any statistically considerable difference between the two groups (, ). Also, higher VEGF levels were found among patients of ASO with smoking history in comparison to patients without smoking history with no statistically considerable difference between the two groups (, ) (Table 6 and Figures 11 and 12).

4.8. Comparison of Ang II as well as VEGF Levels among ASO Patients with or without a History of Diabetes

A higher level of Ang II was found in patients of ASO with a history of diabetes in comparison to those without any diabetes history. There was not any statistically considerable difference between the two groups (, ). Also, a higher VEGF level was observed for ASO patients with a history of diabetes in comparison to those without any diabetes history. There was not any statistically considerable difference between the two groups (, ) (see Table 7 and Figures 13 and 14).

4.9. Comparison of Ang II as well as VEGF Levels among ASO Patients with or without Hypertension

A higher level of Ang II was observed for ASO patients with hypertension history in comparison to those without hypertension, and there was not any statistically considerable difference between the two groups (, ). Also, a higher VEGF level was found for ASO patients with a hypertension history in comparison to those without a history of hypertension. There was not any statistically considerable difference between the two groups (, ) (Table 8 and Figures 15 and 16).

4.10. Comparison of Ang II as well as VEGF Levels among ASO Patients with Different Fontaine Stages

In 60 patients with ASO, the Ang II, as well as VEGF levels among different Fontaine stages, was statistically significant as analyzed by the Kruskal-Wallis test (). Among them, a higher level of Ang II and VEGF was observed for patients with Fontaine III in comparison to patients with Fontaine II with a statistically considerable difference among these groups (). Also, significantly higher levels of Ang II and VEGF were observed for patients with Fontaine IV in comparison to patients with Fontaine II with a statistically considerable difference among these (). Further, significantly higher levels of Ang II and VEGF were found in the Fontaine IV group in comparison to the Fontaine III group () (Table 9 and Figures 17 and 18).

4.11. Comparison of Ang II as well as VEGF Levels among ASO Patients at Different ABI Risk Levels

According to the ABI of patients, the risk grade was divided [27]: the low-risk group (, ), the medium-risk group (, ), and the high-risk group (, ). The levels of Ang II in 60 ASO patients with different risk grades were not statistically significant () as analyzed by ANOVA. Also, there was not any statistically considerable difference in VEGF levels among 60 ASO patients with different risk grades as analyzed by the Kruskal-Wallis test () (Table 10 and Figures 19 and 20).

4.12. Logistic Regression Analysis of Ang II, VEGF, and ASO

The correlation between Ang II, VEGF, and ASO was statistically analyzed. Taking ASO patients as dependent variables while Ang II and VEGF as independent variables, a binary logistic regression analysis was conducted. The results showed that Ang II (, , 95% confidence interval (CI): 0.997-1.343, value = 0.006) and VEGF (, , 95% CI: 1.076-1.115, ) were positively correlated with ASO. These results indicate that Ang II and VEGF could be regarded as risk factors for ASO (Table 11).

4.13. Receiver Operating Curve Analysis

The results from this study reveal that the AUC of Ang II and VEGF in diagnosing ASO was 0.764 (good) and 0.854 (very good), respectively, indicating their value as moderate in diagnosing ASO. On other hand, the AUC of the combined diagnosis of Ang II and VEGF was 0.901 (excellent), indicating that the combined diagnosis of Ang II and VEGF has a higher diagnostic value for ASO. Medcalc software was used to compare the AUC of Ang II, VEGF, and their combined diagnosis. We observed a statistically considerable difference between the two groups (). Among them, the AUC of Ang II and VEGF combined diagnosis was the highest, followed by VEGF and then Ang II with the lowest value (Tables 12 and 13 and Figure 21).

5. Discussion

Atherosclerosis (AS) is the pathological basis of ASO [5], and its pathogenesis is very complex and involves a variety of theories. Among these, the theory of chronic inflammation plays a crucial role in AS pathogenesis and has received widespread attention in the medical community [7]. As a chronic inflammatory disease, AS has the characteristics of classic inflammatory proliferation, degeneration, and exudation. Previous studies mentioned the occurrence and development of AS to be closely related to chronic inflammatory reactions [28–31]. Ang II can promote inflammatory response by inducing the aggregation of a variety of inflammatory cytokines [32]. High level of angiotensin II is one of the typical features of atherosclerosis patients. A large number of studies have confirmed that angiotensin II can effectively activate the Notch1 signaling pathway in a variety of cells. This study also confirmed the effective activation of Notch1 signaling pathway [33], and the overexpression of Notch1 receptor and ligand can stimulate the accumulated macrophages to show an M1-type transformation and release a large number of proinflammatory mediators such as IL-1β and TNF-α. Induce and enhance the inflammatory response of the body, and downregulate the Th2 inflammatory cytokines that inhibit the inflammatory response, such as IL-6, to further promote the inflammatory response [34]. Also, as reported in a previous study, intraplaque angiogenesis plays a critical role in developing AS. VEGF is an important proangiogenic factor found to be involved in regulating and inducing angiogenesis among plaques [35]. Dunmore et al. [36] found that VEGF overexpression existed in unstable plaques, and its content was significantly positively correlated with plaque instability, suggesting that the mismatch between VEGF overexpression and other related factors in plaques may be an important reason for the immaturity of new blood vessels. In addition, changes in the structure or function of VSMCs are the main pathological basis of AS [37, 38] where VSMC proliferation is closely linked to AS development. Ang II is a powerful promoter of VSMC phenotype transformation and plays an important role in inducing VSMC proliferation and migration as well as the progression of AS plaque formation [39, 40]. Dong et al. [41] found that Ang II promoted the secretion of endothelin 1 by vascular endothelial cells, which in turn promoted the production of Ang II by vascular endothelial cells, and the two cooperated to promote the proliferation of VSMC. The possible mechanism was that Ang II, as an autocrine growth factor, could directly induce the mRNA expression of c-myc and fos, thus causing the proliferation of VSMC. Wang et al. [42] also found that Ang II could promote abnormal proliferation of VSMC in rats with spontaneous hypertension, and the AT1R blocker captopril could inhibit the proliferation. In addition, studies have found that VEGF and its receptor are closely related to the proliferation of VSMCs [23]. Therefore, Ang II and VEGF can stimulate an inflammatory response, induce angiogenesis in plaques, and participate in VSMC proliferation and migration with the possibility of promoting the occurrence and development of AS. In another study, Zhou et al. [43] found that the effect of Ang II on AS may be independent of its effect on blood pressure, which is basically consistent with the conclusions of relevant animal studies. It was pointed out that Ang II may also be crucially associated with human AS. In recent studies, CRP has been shown to be directly involved in the formation of AS plaques. During an inflammatory reaction of AS tube wall, Peng and coworkers found that Ang II could induce the production of CRP in VSMCs [44]. Recent studies have also confirmed [45] that Ang II can induce the expression of CRP in macrophages through a variety of signaling pathways, thereby playing a proinflammatory role. Simultaneously, studies have confirmed [20] that if the expression of VEGF and its receptor in AS plaques is significantly increased; then, it indicates new blood vessel formation in AS plaques, depicting a crucial association of VEGF with AS.

In this study, the level of Ang II in ASO patients was considerably higher in comparison to the control group (), which indicates an increase in Ang II level being related to ASO. The mechanism for ASO induction on increasing Ang II level may be linked to induction of inflammatory reaction and the stimulation of VSMC proliferation. Ang II can promote inflammatory response by inducing a variety of inflammatory cytokines to aggregate and activate NF-κB [22]. Excessive Ang II secretion stimulates an abnormal proliferation of VSMCs in blood vessels, activates relevant signaling pathways, promotes the abnormal elevation of inflammatory factors such as interleukin-6 (IL-6) and nitric oxide (NO), causes damage to blood vessels, and then promotes the occurrence of AS [46]. The binary logistic regression analysis showed Ang II to be a risk factor for ASO. The AUC of Ang II was 0.764 (good), which indicates that Ang II has a moderate diagnostic value for ASO, with a sensitivity of 98.3% and a specificity of 66.7%. It can also be seen that Ang II is an effective index to evaluate the severity of ASO disease while having a certain reference value for the diagnosis of ASO. Simultaneously, the results of this study reveal that the VEGF level of ASO patients was considerably higher in comparison to the control group (), indicating that the increase in VEGF level is related to ASO. The mechanism by which the elevated VEGF level promotes the occurrence of ASO may be related to the induction of angiogenesis in AS plaques and the promotion of inflammatory response [22]. Among them, VEGF and its tyrosine kinase receptor pathway make endothelial cells proliferate and migrate, increase vascular permeability, and participate in regulating and inducing angiogenesis. However, in the initial stage, the increase in VEGF level stimulates the abnormal proliferation of vascular endothelial cells, resulting in immature neovascularization [20]. Studies have shown that immature and pathological neovascularization mostly exists in AS unstable plaques [47]. Binary logistic regression analysis showed that Ang II and VEGF were risk factors for ASO. The AUCs of Ang II and VEGF in the diagnosis of ASO were 0.764 (good) and 0.854 (very good), respectively, indicating their moderate diagnostic value for ASO. They have a certain correlation with the occurrence and development of ASO and also reflect the severity of ASO to a certain extent. The AUC was compared with Medcalc software, and it was found that the AUC of Ang II and VEGF together in the diagnosis of ASO was 0.901 (excellent), which was higher than the AUC of these two indicators alone. This clearly indicates that the combined detection of the two indicators is more valuable in the diagnosis of ASO.

In conclusion, Ang II and VEGF were correlated with the occurrence and development of ASO. At the same time, the AUC analysis demonstrates that Ang II and VEGF were highly discriminative of ASO. However, the limitations of the study, due to time constraints, a small sample size, and only established cases, have been analyzed. Hence, a more rigorous, multicenter, larger sample, double-blind study needs to be designed for further analysis.

Data Availability

The data presented in the study may be made available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

This work was supported by a grant from Tai’an Science and Technology Development Fund (2021NS201).

References

K. Zhang, W. Song, D. Li et al., “The association between polymorphism of CARD8 rs2043211 and susceptibility to arteriosclerosis obliterans in Chinese Han male population,” Cellular Physiology and Biochemistry, vol. 41, no. 1, pp. 173–180, 2017.
View at: Publisher Site | Google Scholar
H. Yufen, L. Ming, and Z. Lili, Practical Peripheral Vascular Diseases, Jincheng Press, Beijing, 1st edition, 2005.
L. M. Wiltz-James and J. Foley, “Hospital discharge teaching for patients with peripheral vascular disease,” Critical Care Nursing Clinics of North America, vol. 31, no. 1, pp. 91–95, 2019.
View at: Publisher Site | Google Scholar
B. Zhou, J. She, Y. Wang, and X. Ma, “Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report,” Journal of Thrombosis and Thrombolysis, vol. 50, no. 1, pp. 229–232, 2020.
View at: Publisher Site | Google Scholar
G. K. Hansson, “Inflammation, atherosclerosis, and coronary artery disease,” The New England Journal of Medicine, vol. 352, no. 16, pp. 1685–1695, 2005.
View at: Publisher Site | Google Scholar
M. Bäck, A. Yurdagul Jr., I. Tabas, K. Öörni, and P. T. Kovanen, “Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities,” Nature Reviews Cardiology, vol. 16, no. 7, pp. 389–406, 2019.
View at: Publisher Site | Google Scholar
X. Dai, D. Zhang, C. Wang, Z. Wu, and C. Liang, “The pivotal role of thymus in atherosclerosis mediated by immune and inflammatory response,” International Journal of Medical Sciences, vol. 15, no. 13, pp. 1555–1563, 2018.
View at: Publisher Site | Google Scholar
L. Qingquan and D. Xinqing, “Relationship between angiotensin II and coronary heart disease,” Fujian Journal of Medicine, vol. 34, no. 6, pp. 141-142, 2012.
View at: Google Scholar
A. V. Poznyak, D. Bharadwaj, G. Prasad, A. V. Grechko, M. A. Sazonova, and A. N. Orekhov, “Renin-angiotensin system in pathogenesis of atherosclerosis and treatment of CVD,” International Journal of Molecular Sciences, vol. 22, no. 13, p. 6702, 2021.
View at: Publisher Site | Google Scholar
X. Xiao, C. Zhang, X. Ma et al., “Angiotensin-(1-7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways,” Experimental Cell Research, vol. 336, no. 1, pp. 58–65, 2015.
View at: Publisher Site | Google Scholar
D. Weiss, D. Sorescu, and W. R. Taylor, “Angiotensin II and atherosclerosis,” The American Journal of Cardiology, vol. 87, no. 8A, pp. 25C–32C, 2001.
View at: Google Scholar
G. H. Gibbons, R. E. Pratt, and V. J. Dzau, “Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II,” The Journal of Clinical Investigation, vol. 90, no. 2, pp. 456–461, 1992.
View at: Publisher Site | Google Scholar
R. Inatome, S. Yanagi, T. Takano, and H. Yamamura, “A critical role for Syk in endothelial cell proliferation and migration,” Biochemical and Biophysical Research Communications, vol. 286, no. 1, pp. 195–199, 2001.
View at: Publisher Site | Google Scholar
C. J. Seow, S. C. Chue, and W. S. Wong, “Piceatannol, a Syk-selective tyrosine kinase inhibitor, attenuated antigen challenge of guinea pig airways in vitro,” European Journal of Pharmacology, vol. 443, no. 1-3, pp. 189–196, 2002.
View at: Publisher Site | Google Scholar
N. Ferrara and W. J. Henzel, “Reprint of “Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells”,” Biochemical and Biophysical Research Communications, vol. 425, no. 3, pp. 540–547, 2012.
View at: Publisher Site | Google Scholar
A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. van Oosterom, and E. A. de Bruijn, “Vascular endothelial growth factor and angiogenesis,” Pharmacological Reviews, vol. 56, no. 4, pp. 549–580, 2004.
View at: Publisher Site | Google Scholar
H. Študentová, J. Indráková, P. Petrová et al., “Risk factors of atherosclerosis during systemic therapy targeting vascular endothelial growth factor,” Oncology Letters, vol. 11, no. 2, pp. 939–944, 2016.
View at: Publisher Site | Google Scholar
Y. Shimizu, K. Arima, Y. Noguchi et al., “Vascular endothelial growth factor (VEGF) polymorphism rs3025039 and atherosclerosis among older with hypertension,” Scientific Reports, vol. 12, no. 1, p. 5564, 2022.
View at: Publisher Site | Google Scholar
L. Figueira and J. C. González, “Effect of resveratrol on seric vascular endothelial growth factor concentrations during atherosclerosis,” Clínica e Investigación en Arteriosclerosis, vol. 30, no. 5, pp. 209–216, 2018.
View at: Publisher Site | Google Scholar
J. Pelisek, G. Well, C. Reeps et al., “Neovascularization and angiogenic factors in advanced human carotid artery stenosis,” Circulation Journal, vol. 76, no. 5, pp. 1274–1282, 2012.
View at: Publisher Site | Google Scholar
Y. X. Chen, Y. Nakashima, K. Tanaka, S. Shiraishi, K. Nakagawa, and K. Sueishi, “Immunohistochemical expression of vascular endothelial growth factor/vascular permeability factor in atherosclerotic intimas of human coronary arteries,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 1, pp. 131–139, 1999.
View at: Publisher Site | Google Scholar
S. Chao and Z. Yunxiang, “Expression and clinical significance of vascular endothelial cell growth factor and homocysteine in patients with lower extremity arteriosclerosis obliterans,” Medical Theory and Practice, vol. 35, no. 2, pp. 309–311, 2022.
View at: Google Scholar
A. H. Dorafshar, N. Angle, M. Bryer-Ash et al., “Vascular endothelial growth factor inhibits mitogen-induced vascular smooth muscle cell proliferation1, 2,” The Journal of Surgical Research, vol. 114, no. 2, pp. 179–186, 2003.
View at: Publisher Site | Google Scholar
Vascular Surgery Group, Surgery Society of Chinese Medical Association, “Guidelines for diagnosis and treatment of arteriosclerosis obliterans of lower extremity,” Chinese Journal of Vascular Surgery (Electronic Edition), vol. 7, no. 3, pp. 145–151, 2015.
View at: Google Scholar
L. Norgren, W. R. Hiatt, J. A. Dormandy, M. R. Nehler, K. A. Harris, and F. G. R. Fowkes, “Inter-society consensus for the management of peripheral arterial disease (TASC II),” Journal of Vascular Surgery, vol. 45, no. 1, pp. S5–67, 2007.
View at: Publisher Site | Google Scholar
W. Zhankun, Correlation between lipoprotein phospholipase A2, common femoral artery intima-media thickness and traditional Chinese medicine syndrome type of occlusive arteriosclerosis obliterans, Shandong University of Chinese Medicine, 2020.
X. Shuai, C. Jianqiu, and L. Yankui, “The value of plasma β2-mg and HCY in the risk classification and prognosis assessment of lower extremity atherosclerosis,” Chinese Journal of General Surgery, vol. 21, no. 6, pp. 675–681, 2012.
View at: Google Scholar
Y. Zhu, X. Xian, Z. Wang et al., “Research progress on the relationship between atherosclerosis and inflammation,” Biomolecules, vol. 8, no. 3, p. 80, 2018.
View at: Publisher Site | Google Scholar
X. Zhang, Z. Ren, and Z. Jiang, “EndMT-derived mesenchymal stem cells: a new therapeutic target to atherosclerosis treatment,” Molecular and Cellular Biochemistry, vol. 2022, pp. 1–11, 2022.
View at: Publisher Site | Google Scholar
Z. Y. Liang, C. W. Qian, T. H. Lan, Q. H. Zeng, W. H. Lu, and W. Jiang, “Regulatory T cells: a new target of Chinese medicine in treatment of atherosclerosis,” Chinese Journal of Integrative Medicine, vol. 27, no. 11, pp. 867–873, 2021.
View at: Publisher Site | Google Scholar
N. Ruparelia and R. Choudhury, “Inflammation and atherosclerosis: what is on the horizon?” Heart, vol. 106, no. 1, pp. 80–85, 2020.
View at: Publisher Site | Google Scholar
X. Zhang, J. Yang, X. Yu, S. Cheng, H. Gan, and Y. Xia, “Angiotensin II-induced early and late inflammatory responses through NOXs and MAPK pathways,” Inflammation, vol. 40, no. 1, pp. 154–165, 2017.
View at: Publisher Site | Google Scholar
J. R. Wu, J. L. Yeh, S. F. Liou, Z. K. Dai, B. N. Wu, and J. H. Hsu, “Gamma-secretase inhibitor prevents proliferation and migration of ductus arteriosus smooth muscle cells through the Notch3-HES1/2/5 pathway,” International Journal of Biological Sciences, vol. 12, no. 9, pp. 1063–1073, 2016.
View at: Publisher Site | Google Scholar
S. W. Maalouf, C. L. Smith, and J. L. Pate, “Changes in microRNA expression during maturation of the bovine corpus luteum: regulation of luteal cell proliferation and function by microRNA-34a,” Biology of Reproduction, vol. 94, no. 3, p. 71, 2016.
View at: Publisher Site | Google Scholar
K. Nakagawa, Y. X. Chen, H. Ishibashi et al., “Angiogenesis and its regulation: roles of vascular endothelial cell growth factor,” Seminars in Thrombosis and Hemostasis, vol. 26, no. 1, pp. 061–066, 2000.
View at: Publisher Site | Google Scholar
B. J. Dunmore, M. J. McCarthy, A. R. Naylor, and N. P. J. Brindle, “Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques,” Journal of Vascular Surgery, vol. 45, no. 1, pp. 155–159, 2007.
View at: Publisher Site | Google Scholar
A. Frismantiene, M. Philippova, P. Erne, and T. J. Resink, “Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity,” Cellular Signalling, vol. 52, pp. 48–64, 2018.
View at: Publisher Site | Google Scholar
Y. Chen, L. Liang, C. Wu et al., “Epigenetic control of vascular smooth muscle cell function in atherosclerosis: a role for DNA methylation,” DNA and Cell Biology, vol. 41, no. 9, pp. 824–837, 2022.
View at: Publisher Site | Google Scholar
N. Shi and S. Y. Chen, “Mechanisms simultaneously regulate smooth muscle proliferation and differentiation,” Journal of Biomedical Research, vol. 28, no. 1, pp. 40–46, 2014.
View at: Publisher Site | Google Scholar
E. R. Pfaltzgraff and D. M. Bader, “Heterogeneity in vascular smooth muscle cell embryonic origin in relation to adult structure, physiology, and disease,” Developmental Dynamics, vol. 244, no. 3, pp. 410–416, 2015.
View at: Publisher Site | Google Scholar
D. Xiaoyan, Z. Guiqing, X. Mingming et al., “Effect of Captopril on endothelin and angiotensin ? in rabbits with atherosclerosis and its correlation with proto-oncogenes c-myc and c-fos,” Chinese Journal of Arteriosclerosis, vol. 3, pp. 217–220, 2002.
View at: Google Scholar
W. Xiangyu, W. Jiaobao, J. Xueqing, W. Huajun, and X. Changsheng, “Relationship between abnormal proliferation of aortic smooth muscle cells and endogenous renin-angiotensin system in spontaneously hypertensive rats,” Chinese Journal of Arteriosclerosis, vol. 3, pp. 212–216, 1997.
View at: Google Scholar
Z. Jingxiong, H. Chunling, C. Xiaoyu et al., “Association between angiotensin ? and atherosclerosis in type 2 diabetes mellitus,” Chinese Journal of Gerontology, vol. 34, no. 24, pp. 6905–6907, 2014.
View at: Google Scholar
N. Peng, J. T. Liu, D. F. Gao, R. Lin, and R. Li, “Angiotensin II-induced C-reactive protein generation: inflammatory role of vascular smooth muscle cells in atherosclerosis,” Atherosclerosis, vol. 193, no. 2, pp. 292–298, 2007.
View at: Publisher Site | Google Scholar
M. Li, J. Liu, C. Han, B. Wang, X. Pang, and J. Mao, “Angiotensin II induces the expression of c-reactive protein via MAPK-dependent signal pathway in U937 macrophages,” Cellular Physiology and Biochemistry, vol. 27, no. 1, pp. 63–70, 2011.
View at: Publisher Site | Google Scholar
L. Dongdong, L. Shaokui, G. Xinyu, W. Xiaomei, and W. Cuirong, “Resveratrol inhibits angiotensin ?/TLR4/NF-KB in regulating inflammation and oxidative stress injury of rat vascular smooth muscle cells,” Chinese Journal of Evidence-based Cardiovascular Medicine, vol. 11, no. 12, pp. 1461–1467, 2019.
View at: Google Scholar
C. Yiyao, Study on the pathology, morphology and related cellular mechanism of carotid atherosclerotic plaque, Peking Union Medical College, 2019.

Copyright

Copyright © 2023 Yulian Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

360

Downloads

317

Citations