Blood monocytes in maintaining the balance of vascular endothelial injury and repair process in ischemic cardiomyopathy

Abstract

Highlights. The features of subsets of monocytes in combination with the levels of desquamated endotheliocytes, endothelial damage and regeneration mediators and progenitor cell migration-enhancing factors in patients with coronary heart disease and with/without ischemic cardiomyopathy were analyzed. For the first time it was shown that in patients with ischemic cardiomyopathy, compared with CHD patients without cardiomyopathy, higher desquamation of the endothelium is associated with a deficiency of non-classical monocytes and reduced migration of progenitor endothelial cells (VEGFR2+-monocytes) with regenerative potential across the bone marrow due to a deficiency of the HIF-1α mediator in the blood.Background. The development of ischemic cardiomyopathy (ICM) is an understudied process, and one of its elements may be insufficient regeneration of blood vessels due to an imbalance of subsets of monocytes in the blood.Aim. To assess subsets of monocytes and desquamated endothelial cells in combination with endothelial damage and regeneration mediators in the blood of patients with coronary heart disease (CHD) and with/without ICM.Methods. The study included 30 patients with ICM, 22 patients with coronary heart disease without cardiomyopathy aged 55–69 years, and 18 healthy donors. In whole blood, the populations of CD45–CD146+ desquamated endothelial cells and progenitor endothelial cells related to CD14+VEGFR2+  monocytes, intermediate CD14++CD16+   and  non-classical  CD14+CD16++   monocytes  were  assessed  by flow cytometry  using  the  appropriate  monoclonal  antibodies  (BD  Biosciens, USA). In blood plasma, the levels of hypoxia-inducible factor HIF-1α, monocyte chemoattractant protein MCP-1 and matrix metalloproteinase MMP-9 were assessed by enzyme immunoassay. The results of the analysis were considered significant at p<0.05.Results. The number of progenitor and desquamated endothelial cells was increased in both groups of patients with coronary artery disease. At the same time, in patients with ICM, the number of progenitor endothelial cells did not reach the number noted in patients with CHD without cardiomyopathy, while the number of desquamated endothelial cells reached the number noted in CHD patients without cardiomyopathy. There was a deficiency of non-classical monocytes and HIF-1α in the blood of patients with ICM, and an excess of intermediate monocytes and MCP-1 was observed in CHD patients without cardiomyopathy. The concentration of MMP-9 in patients with CHD corresponded to the norm, regardless of the presence of ICM.Conclusion. In ICM, in contrast to CHD without cardiomyopathy, vascular damage is associated with a deficiency of nonclassical monocytes and reduced endothelial repair due to insufficient migration of progenitor endothelial cells across the bone marrow due to HIF-1α deficiency in the blood.