Rosuvastatin stimulates clonogenic potential and anti‐inflammatory properties of endothelial progenitor cells

Abstract

EPCs (endothelial progenitor cells) exert vasculoprotective effects and can be used for regenerative therapies. However, several isolation protocols have been described, with inconsistent results. Statins are among the most effective compounds that stimulate EPC numbers in vivo and ex vivo. We aim to describe the effects of rosuvastatin on different subtypes of putative EPCs. EPCs were cultured from mononuclear cells of blood donors and isolated according to three protocols: CFU-EC (colony forming units-endothelial cells), early (or 'monocytic') EPCs and late outgrown EPCs. Rosuvastatin (0.1-100 nM) was added at the beginning of culture (T0) or after the initial adhesion step (T1). Polarization of monocytic EPCs was assessed as expression of proinflammatory M1 markers (CD68 and CCR2) or anti-inflammatory M2 markers (CX3CR1, CD163, CD206). We found that 1 nM rosuvastatin increased the number of CFU-EC and late EPCs by about 3-fold, while lower concentrations had no significant effects. Rosuvastatin (0.1 nM) increased AcLDL+Lectin+ early EPCs by about 60%, while higher concentrations exerted inhibitory effects on early EPCs. Addition of rosuvastatin at T0 was more effective in stimulating CFU-EC and early EPCs, while addition at T1 was more effective in stimulating late EPCs. Rosuvastatin had no effects on proliferation rate of CFU-EC, early EPCs and late EPCs. We also found that 0.1 nM rosuvastatin reduced the M1/M2 ratio in early EPCs, which retain monocytic features. In conclusion, we show that rosuvastatin had significant stimulatory effects on EPCs irrespective of the culture protocol. Rosuvastatin also induced anti-inflammatory polarization of monocytic EPCs.

Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis

“…Relationships between circulating endothelial compartment and IPF characteristics Differences in endothelial cells and progenitors were not associated to the smoking status as it has been shown in other models [37] or with medications with a potential impact on these cells [38] (data not shown). In contrast, they were markedly associated with the Diffusing capacity of the lung for carbon monoxide (DL CO ).…”

Liver X Receptor Modulates Diabetic Retinopathy Outcome in a Mouse Model of Streptozotocin-Induced Diabetes

“…Hypercholesterolemic patients, free of diabetes, have been found to have a reduced number of circulating EPCs with impaired function (39,40). A dose-dependent decrease in EPC survival and function was observed with exposure to oxidized LDL, and numerous in vitro and in vivo studies demonstrated that hydroxymethylglutaryl-CoA reductase inhibitors (statins) potently enhance EPC numbers and function (41–43). Hypercholesterolemia has also been linked to monocytosis in atherosclerosis (44).…”

Telomere/Telomerase System: A New Target of Statins Pleiotropic Effect?

“…Statins were reported to increase the number of EPC and to promote their functional activity in vivo and ex vivo [88][89][90]. Even if several EPC isolation protocols have been described for the isolation of monocytic or endothelial cell precursors, rosuvastatin showed stimulatory effects on EPCs, independently of the culture protocol [91]. Moreover, statins were reported to directly induce the differentiation of monocytes or CD34-positive hematopoietic precursor cells into EPCs and cardiomyogenic cells [92].…”