Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure

Table 1

Effect of CBD in different cardiomyopathy experimental models.

Biological subject	CBD concentration	Experimental model	CBD treatment key results	Ref
In vitro models
Human umbilical artery smooth muscle cells	0.1-10 μM	ROS modulation with NAC	Protective effect against aberrant proliferation and migration by an increased expression of HO-1	[18]
Human aortic endothelial cells	10 μM	High glucose/insulin	Decreased inflammatory (↓NF-κβ,) proliferation (↓JNK, ↓p70s6K), and increased survival (↑Akt) pathways	[19]
Human coronary artery endothelial cells	1.5, 3, 4.5, 6 μM	High glucose-induced endothelial cell inflammatory response	Reduced mitochondrial superoxide generation, NF-κβ activation, and ICAM-1 and VCAM-1 expression	[20]
Primary human cardiomyocytes	4 μM	Diabetic cardiomyopathy by high glucose culture	Decrease of oxidative/nitrosative stress and NF-κβ activation	[11]
Rat ventricular myocytes	1-10 μM	Normal conditions	Inhibition of L-type Ca^2+ channels	[22]
Cardiomyocytes(iPSC)	1 μM	Ischemia/reperfusion and LPI administration	Reduced Ca^2+ overload providing ischemia/reperfusion protection (↓GPR55 activation, ↓RhoA, ↓ROCK)	[23]
Ex vivo models
Zucker diabetic rat aorta	10 μM	Diabetic cardiomyopathy	Improved acetylcholine-induced vasorelaxation	[25]
Rat mesenteric arteries	10 mg/kg	Diabetic cardiomyopathy	Endothelium COX- and NO-dependent enhanced vasorelaxation of Ach	[26]
Human mesenteric arteries	10 μM	Vasorelaxation	Promotes vasorelaxation via CB1 and the TRP activation and increased eNOS expression	[19]
Rat aorta	10 μM	Contraction stress by a combination of U46619 and methoxamine	Increase vasorelaxation of precontracted aorta by inhibition of calcium channels and increased transcriptional activity of PPARγ	[27]
In vivo models
Primary and secondary hypertension rat model	10 mg/kg	Spontaneous and deoxycorticosterone acetate-salt hypertension	Reduction of cardiac and plasma oxidative stress (increased GSH and decreased GSSG) both in heart and plasma	[29]
Spontaneously hypertensive rats	3, 10 and 30 mg/kg	Hypertension	A dose-dependent decrease in HR and blood pressure mediated via TRPV1	[30]
In vivo rat I-R model	5 mg/kg	LAD ligation ischemia/reperfusion injury	A decrease in the infarct size and reduction of inflammation molecules like IL-6	[31]
In vivo I-R rabbit model	100 μg/kg	Acute reperfusion myocardial infarction	Reduced infarct size and facilitated restoration of left ventricular function	[32]
In vivo rat I-R model	10, 50 μg/kg	LAD ligation ischemia/reperfusion injury	Reduction of the infarct size and ventricular arrhythmias; Inhibition of collagen-induced platelet aggregation	[33]
In vivo I-R rat model	50 μg/kg	LAD ligation ischemia/reperfusion -induced ventricular arrhythmias	Decreased incidence and duration of ventricular tachycardia and the total length of arrhythmias by activation of the adenosine receptor	[34]
Zucker diabetic rat	10 μM	Diabetic cardiomyopathy	Improvement on vasorelaxation by involvement of the CB2 receptor and the enhancement of COX and SOD activity	[35]
Diabetic cardiomyopathy mice model	1, 10, 20 mg/kg	Streptozotocin induced diabetic cardiomyopathy	Attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrosative stress, inflammation, and cell death	[11]
Autoimmune myocarditis mice model	10 mg/kg	MyHCα334–352 induced autoimmune myocarditis	Attenuated the CD3^+ and CD4^+ T cell-mediated inflammatory response and injury, and myocardial fibrosis	[5]
Doxorubicin-induced cardiomyopathy mice model	5 mg/kg	Doxorubicin-induced cardiomyopathy	Decreased serum creatine kinase-MB, cTnT, cardiac malondialdehyde, TNF-α, NO and Ca^2+ levels, increased glutathione, selenium, and zinc ions levels	[36]
Doxorubicin-induced cardiomyopathy mice model	10 mg/kg	Doxorubicin-induced cardiomyopathy	Attenuated oxidative and nitrative stress, improved mitochondrial function, and biogenesis	[37]
In vivo rat stress model	1-72 mg/kg	Restraint stress	Abolished increase of HR and MAP by activation of 5-HT1A receptor	[38–41]