Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease

Abstract

The circulating form of endothelial progenitors cells (EPCs) are derived from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34+ HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function.

Separate mechanisms cause anemia in ischemic vs. nonischemic murine heart failure

“…This is in line with the decline in bone marrow hematopoiesis observed in patients with coronary artery disease (18). We also showed that inhibition of TNF-␣ almost completely restored CD34 ϩ colony formation and decreased the fraction of apoptotic CD34 ϩ cells in the ischemic CHF mice but not in nonischemic CHF mice.…”

Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients

“…Moreover, the number and the functional activity of EPCs have been reported to decrease with hypertension, diabetes mellitus and the coexistence of multiple classical cardiovascular risk factors. [4][5][6][7][8][9][10][11]. Levels of EPCs are also inversely correlated to progression of coronary heart disease.…”

Modification of the detrimental effect of TNF‐α on human endothelial progenitor cells by fasudil and Y27632

“…However, the beneficial outcome of EPC infusion critically depends on the cell number and differentiation factors within the tissue [1]. Correlative studies suggested that number of EPCs inversely correlate to cardiovascular risk factors among apparently healthy people and in patients with coronary heart disease (CHD) [2,3], which show a functional impairment of EPCs, both in the bone marrow as well as when these cells are mobilized into the blood as circulating progenitors [9]. Reduced EPC number has been reported in diabetic patients and in individuals that suffered a stroke [10,11].…”