Circulating Humoral Factors and Endothelial Progenitor Cells in Patients With Differing Coronary Collateral Support

Abstract

Background-The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation. Methods and Results-Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI Ͻ0.25) compared with those with adequate (CFI Ն0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (rϭϪ0.61, PϽ0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor 165 , or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (rϭ0.75, PϽ0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (PϽ0.05) and 70% (PϽ0.05), respectively. Conclusions-In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.

Increase in Circulating CD34-Positive Cells in Patients with Angiographic Evidence of Moyamoya-like Vessels

“…T Yoshihara et al patients with myocardial ischemia (Lambiase et al, 2004). In this study, we show, for the first time, a correlation between neovascularization of the cerebral arterial circulation and increased levels of circulating CD34 + cells.…”

Working hypothesis to redefine endothelial progenitor cells

“…Subsequent multivariate analysis revealed hypertension to be the greatest risk factor associated with arrested CAC migration. 73 Lambiase et al 76 corroborated the relationship between circulating PB CAC concentration and clinically diagnosed CAD, finding that the CAC concentration was reduced by 70-75% when examining the extent of collateral coronary vessel development in 30 patients with left anterior descending CAD. In other studies, severity of type II diabetes correlated with the concentration of CACs, 78 as did hemodialysis, 75 further indicating a potentially protective role for circulating EPCs.…”

“…65 Changes in CAC concentration parallel the observed trends of CFU-EC concentration in patients with cardiovascular disease and risk, which provides further support for the EPC protective hypothesis. [72][73][74][75][76][77][78] Vasa et al 73 observed that as the number of risk factors for coronary artery disease (CAD) increased (including age, sex, hypertension, diabetes, smoking, family history, and low-density lipoprotein (LDL) cholesterol levels), the CAC concentration in PB decreased, with smoking being the most significant risk factor for low CAC concentration. Vasa et al 73 also included a comparison of migratory activity of CACs to individual CAD risk factors.…”

“…Interestingly, both ECFCs and CACs were found to increase in concentration in relation to the severity of CAD; the patients with the most severe CAD were shown to have the highest circulating EPC concentrations, contradicting the results of similar studies. 46,76,92 To our knowledge, this remains one of only a few studies to date which has examined circulating ECFC concentrations in a human pathological condition. 80 …”

Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

“…After overnight fast, patients' venous blood samples were obtained from a forearm vein and processed within 1-2 h. Peripheral blood progenitor cells were analyzed for the expression of cell surface antigens with direct three-color analysis using fluorescein isothiocyanate-conjugated, phycoerythrin (PE)-conjugated and allophycocyanin-conjugated monoclonal antibodies (mAbs) by flow-cytometry analysis (FACSCalibur; Becton Dickinson, Franklin Lakes, NJ, USA, http:// www.bd.com), as previously reported. 33,34 Briefly, before staining with specific mAbs, cells were treated with fetal calf serum for 10 min, and then the samples were washed with buffer containing phosphate-buffered saline and 0.5% bovine albumin. Thereafter, 150 ml of peripheral blood was incubated with 10 ml of fluorescein isothiocyanate-conjugated anti-human CD34 mAb (Becton Dickinson), with 5 ml of allophycocyanin-conjugated anti-human CD133 mAb (Miltenyi Biotec, Bergisch Gladbach, Germany) and 10 ml of PE-conjugated anti-human kinase-insert domain receptor (KDR) mAb (R&D Systems, Minneapolis, MN, USA), followed by incubation at 4 1C for 30 min.…”