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

Table 2

Summary of currently available clinical studies on human plaque macrophages.

Authors	Year	Sample size	Main finding	Reference
Brand et al.	1996	18 subjects	Atherosclerotic lesion in the aorta and carotid arteries contains a large proportion of NF-kB-positive macrophages (i.e., M1 macrophages) when compared to healthy arterial segments	[75]
Johnson et al.	2014	79 CEA specimens	Vulnerable lesions with a large necrotic core contained less MMP14^loTIMP3^hi-M2 macrophages	[76]
Stöger et al.	2012	22 ruptured carotid atherosclerosis specimens and 22 adjacent stable controls	In carotid plaques, CD68+HLA-DP/Q/R+ M1 macrophages are enriched near the rupture-prone shoulder. On the other hand, M2 macrophages were enriched on the adventitial side of the vessel	[77]
Shaikh et al.	2012	32 carotid endarterectomy specimens, 25 femoral artery endarterectomy specimens	Carotid artery plaques have a larger necrotic core and contain more M1 macrophages when compared to femoral artery plaques	[78]
van Dijk et al.	2016	110 human perirenal aortic plaques	M2 and M1 macrophages are both enriched within progressive and vulnerable atherosclerotic plaques	[79]
Howard et al.	2015	1640 carotid artery plaques from patients undergoing CEA for secondary stroke prevention	CD68+ macrophage plaque content was associated with a 5-year stroke risk based on the ECST patient database	[80]
Hellings et al.	2008	500 carotid endarterectomy specimens	A high macrophage infiltration was associated with a high risk of ipsilateral carotid restenosis	[81]
Hellings et al.	2010	818 carotid endarterectomy specimens	Macrophage infiltration did not predict the 3-year risk of cardiovascular death or nonfatal stroke or nonfatal myocardial infarction. On the other hand, plaque neovascularization was associated with the relevant outcomes	[82]
Scholtes et al.	2012	236 subjects undergoing carotid endarterectomy for secondary stroke prevention	The proportion of MMP12+ macrophages was associated with major adverse cardiovascular events and stroke at 3 years	[83]
Gaemperli et al.	2012	9 patients with stroke due to carotid atherosclerosis and 27 subjects with asymptomatic carotid atherosclerosis	In vitro imaging of plaque macrophage infiltration using the macrophage-specific tracer PK11195 allowed to discriminate symptomatic vs. asymptomatic subjects	[84]

M1: proinflammatory M1 macrophages; M2: homeostasis-promoting M2 macrophages; CEA: carotid endarterectomy; MMP: matrix metalloproteinase; TIMP: tissue inhibitor of matrix metalloproteinase.