The role of monocytes in atherosclerotic coronary artery disease

Figures & data

Figure 1. Implication of monocytes in atherogenesis. COX = cyclo-oxygenase; Ecs = endothelial cells; GM-CSF = granulocyte–macrophage colony-stimulating factor; HIF-1 = hypoxia-inducible factor; HSP = heat shock protein; ICAM-1 = intercellular adhesion molecule 1; IL = interleukin; LOX = lipoxygenase; LPS = lipopolysaccharide; MAPK = mitogen-activated protein kinase; MCP-1 = monocyte chemotactic protein-1; M-CSF = macrophage colony-stimulating factor; MMPs = matrix metalloproteinases; MPO = myeloperoxidase; NFκB = nuclear factor κB; SRs = scavenger receptors; TIR = Toll/interleukin-1 receptor; TLR4 = Toll-like receptor 4; TNF = tumour necrosis factor; VCAM-1 = vascular cell adhesion molecule 1; VEGF = vascular endothelial growth factor.

Table I. Relationship between the monocyte counts/subtypes and left ventricular dysfunction/remodelling after myocardial infarction.

Study	Study population	Principal findings
Maekawa et al. (97)	149 patients with first Q-wave acute MI	Monocyte count ≥900/mm^3 was an independent determinant of pump failure (relative ratio 9.83), LV aneurysm (relative ratio 4.78), and cardiac events (relative ratio 6.30), including readmission for heart failure, recurrent MI, and cardiac deaths
Hojo et al. (98)	30 patients with ST-elevation MI	Higher VEGF production by peripheral blood mononuclear cells was associated with improvement of LV systolic function
Iwama et al. (99)	55 patients with acute MI and 43 controls	Plasma levels of placental growth factor on day 3 were negatively correlated with the LVEF, and positively correlated with both acute phase peak peripheral monocyte counts and chronic phase changes in LVEF
Tsujioka et al. (100)	36 patients with acute MI	Peak counts of CD14^+CD16^− monocytes, but not CD14^+CD16^+ monocytes, were negatively associated with the extent of myocardial salvage. Peak counts of CD14^+CD16^+ monocytes, but not CD14^+CD16^+ monocytes, were negatively correlated with recovery of LVEF 6 months after MI
Methe et al. (17)	28 patients with acute MI, 40 patients with unstable angina, 20 patients with coronary artery disease, 30 healthy controls	Circulating TLR4^+/CD14^+ monocytes were ∼2.5-fold increased in ACS compared to stable coronary artery disease and healthy controls
Bruno et al. (101)	16 patients with acute MI, 15 healthy controls	CD14^+/KDR^+ cells, but not CD14^+/KDR^− cells, had pro-angiogenic properties in in vitro and in vivo experiments
Dresske et al. (102)	Lewis female rats with MI	Delivery of cells derived from peripheral blood monocytes improved LV function after MI

LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction.

Table II. Monocytes and congestive heart failure.

Study	Population	Principal findings
Satoh et al. (103)	52 patients with acute MI, 20 controls	14 days after acute MI, levels of HSP70 were higher in patients with HF compared to those without HF
de Lemos et al. (104)	4244 patients with ACS	MCP-1 levels >238 pg/mL were independently associated with mortality (hazard ratio 2.16) and with composite end-points of death or MI; death, MI, or HF; and cardiovascular death, MI, readmission for ACS, or stroke
Satoh et al. (105)	65 patients with acute MI and 20 controls	Base-line TLR4 expression and plasma levels of inflammatory cytokines (IL-6, GM-CSF, and TNFα) were higher in MI patients with HF compared to those without HF
Sheu et al. (106)	43 patients with ST-elevation MI and 20 controls	Plasma levels of TNFα and monocyte TLR4 expression were significantly higher in patients with acute MI than in healthy controls; high TLR4 expression was independent predictor of 30-day major adverse cardiac events
Dahl et al. (107)	Experimental rat model	Patients with chronic HF had significantly increased expression herpesvirus entry mediator on and within the failing myocardium
Satoh et al. (108)	46 patients with HF and 22 controls	In patients with HF, especially those with severe HF, high expression TNF-converting enzyme in circulating mononuclear cells was associated with increased expression of TNFα

MI = myocardial infarction; HF = heart failure.

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