Effect of vitamin D on endothelial progenitor cells function

by Yoav Hammer, Alissa Soudry, Amos Levi, Yeela Talmor-Barkan, Dorit Leshem-Lev, Joel Singer, Ran Kornowski, Eli I. Lev

Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD) and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function.

To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes.

Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8%) and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs), their viability (measured by MTT assay), KLF-10 levels and angiogenic markers were evaluated after 1 week of culture.

In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol [EPC CFUs: 1.25 (IQR 1.0–2.0) vs. 0.5 (IQR 0.5–1.9), p < 0.001; MTT:0.62 (IQR 0.44–0.93) vs. 0.52 (IQR 0.31–0.62), p = 0.001]. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability [MTT: 0.23 (IQR 0.11–0.46) vs. 0.19 (0.09–0.39), p = 0.04], but without differences in CFU count or angiopoietic markers.

In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.