Abstract 14276: Recruitment of Inflammatory and Regenerative Cells in CAD is Selectively Regulated by Kinin Signaling
Background: In coronary artery disease (CAD), recruitment of inflammatory cells from the blood to the arterial wall is enhanced, while the migratory capacity of angiogenic/reparative circulating progenitor cells (CPC) seems to be impaired. We and others have shown that kinins are chemotactic for inflammatory as well as pro-angiogenic cells.
Hypothesis: Here we examine the effect of endothelium-derived kinins on selective recruitment of inflammatory monocytes versus reparative CPC of CAD patients and age-matched healthy controls (H) from the circulating blood to the vessel wall.
Methods & Results: In H donors, expression of the kinin receptors B1R and B2R was virtually absent on lymphocytes, intermediate on CD14hi inflammatory monocytes and highest on CD34+KDR+ and CD34+CXCR4+ CPC, as detected by flow cytometry. In an in vitro adhesion assay, adhesion of total leukocytes from H to human coronary artery endothelial cells was only marginally affected by kinin receptor blockade, while B2R blockade specifically increased adhesion of H CD14hi inflammatory monocytes (+18.5% vs. baseline) and decreased adhesion of CD34+CXCR4+ CPC (−16.9% vs. baseline). B1R blockade had only minimal effects on cell type-specific adhesion in H. In CAD, B2R expression was reduced in CD34+KDR+ and CD34+CXCR4+ CPC (−59.6% and −88.1% vs. H). B1R was reduced only in CD34+KDR+ CPC (−84.2% vs. H), but not on CD34+CXCR4+ CPC. CAD total leukocytes adhered less under B1R (−25.9% vs. baseline) or B2R (−16.4% vs. baseline) blockade. In contrast to H, B2R blockade only marginally affected CD14hi monocyte adhesion in CAD, but reduced CD34+CXCR4+ CPC (−15.6% vs. baseline) adhesion. Interestingly, B1R blockade increased adhesion CD34+CXCR4+ CPC (+25.0% vs. baseline) of CAD, but not of H.
Conclusions: Here we show for the first time that kinin receptor expression and—signaling are differentially modulated on distinct circulating cell populations in CAD. Notably, inhibitory effects of B2R on inflammatory monocyte adhesion are markedly impaired in CAD. Selective kinin receptor modulation may provide an interesting tool to beneficially impact on vascular recruitment of inflammatory vs. vascular repair cells, likely a critical process for the progression of atherosclerotic vascular disease.
- © 2010 by American Heart Association, Inc.