Review Article

The Role of Monocytes and Macrophages in Human Atherosclerosis, Plaque Neoangiogenesis, and Atherothrombosis

Table 1

Summary of currently available studies on human circulating monocytes subsets and atherosclerosis.

AuthorsYearSample sizeMonocyte subpopulation of interestMain resultReference

Jaipersad et al.2014160 individuals with carotid artery stenosisCCR2-expressing monocytes, subdivided into classical, intermediate, and nonclassical subsetsClassical CD14hiCD16-CCR2+ monocytes are associated with the degree of carotid stenosis and plaque neovascularization evidenced by CEUS[63]
Ammirati et al.201664 individuals with intermediate carotid artery stenosisCD14+ monocytes subdivided into classical, intermediate, and nonclassical subsetsTotal CD14+ monocytes and nonclassical CD14hiCD16- monocytes are reduced in subjects with higher CEUS-evidenced neovascularization[64]
Ammirati et al.20189 individuals with intermediate carotid artery stenosisCD14+ monocytes subdivided into classical, intermediate, and nonclassical subsetsPeople with a stronger uptake of activated macrophage-specific radiotracer PK11195 had reduced circulating total CD14+ monocytes and nonclassical CD14hiCD16- monocytes[65]
Justo-Junior et al.201818 controls, 34 individuals with CVRF, 32 patients with stable angina, and 16 patients with unstable anginaClassical, intermediate, and nonclassical circulating monocytesIntermediate CD14hiCD16+ monocytes were elevated in unstable angina patients. They also displayed high expression of PRRs[22]
Yamamoto et al.2016389 CAD patientsPeripheral blood monocytesA high monocyte count predicted future cardiovascular events in CAD patients[66]
Zhuang et al.201748 patients with unstable angina and 31 patients with STEMIClassical, intermediate, and nonclassical monocytesPatients with evidence of thin cap fibroatheroma on OCT had significantly mode circulating intermediate CD14hiCD16+ monocytes[67]
Lorenzen et al.2011191 subjects undergoing hemodialysisCD14+TLR4+ monocytesNo association between CD14+TLR4+ and cardiovascular deaths or cardiovascular events[68]
Collin et al.201523 patients with nonobstructive CAD undergoing IVUSCD14+BAP+OCN+ monocytesCD14+BAP+OCN+ monocytes correlate with the presence of a large necrotic core within coronary artery plaques[70]
Meeuwsen et al.2019175 subjects undergoing carotid endarterectomy (85% symptomatic, 15% asymptomatic)Total, classical, intermediate, and nonclassical monocytesNo association between monocyte subpopulations and plaque features of vulnerability. No association between monocyte subpopulations and major adverse cardiovascular events at 3 years of follow-up[72]

CEUS: contrast-enhanced ultrasound; CAD: coronary artery disease; CVRF: cardiovascular risk factors; OCT: optical coherence tomography; IVUS: intravascular ultrasound.