Pravastatin Promotes Endothelial Colony-Forming Cell Function, Angiogenic Signaling and Protein Expression In Vitro

• Published in: Journal of clinical medicine Vol. 10; no. 2; p. 183
• Main Authors: Meyer, Nadia, Brodowski, Lars, Richter, Katja, von Kaisenberg, Constantin S, Schröder-Heurich, Bianca, von Versen-Höynck, Frauke
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.01.2021; MDPI
• Subjects: Angiogenesis; Apoptosis; Cardiovascular disease; Cell growth; cell therapy; Clinical medicine; Coronary vessels; endothelial colony-forming cells; endothelial dysfunction; endothelial progenitor cells; Flow cytometry; Growth factors; Hypertension; Kinases; Mortality; pravastatin; Preeclampsia; Proteins; statins; Umbilical cord; Vein & artery diseases; Wound healing; United States > US; Switzerland; Germany; cardiovascular disease; endothelial colony-forming cells; angiogenesis; cell therapy; endothelial progenitor cells; pravastatin; statins; preeclampsia; endothelial dysfunction; vascular repair
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm10020183

Endothelial dysfunction is a primary feature of several cardiovascular diseases. Endothelial colony-forming cells (ECFCs) represent a highly proliferative subtype of endothelial progenitor cells (EPCs), which are involved in neovascularization and vascular repair. Statins are known to improve the outcome of cardiovascular diseases via pleiotropic effects. We hypothesized that treatment with the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor pravastatin increases ECFCs' functional capacities and regulates the expression of proteins which modulate endothelial health in a favourable manner. Umbilical cord blood derived ECFCs were incubated with different concentrations of pravastatin with or without mevalonate, a key intermediate in cholesterol synthesis. Functional capacities such as migration, proliferation and tube formation were addressed in corresponding in vitro assays. mRNA and protein levels or phosphorylation of protein kinase B (AKT), endothelial nitric oxide synthase (eNOS), heme oxygenase-1 (HO-1), vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and endoglin (Eng) were analyzed by real time PCR or immunoblot, respectively. Proliferation, migration and tube formation of ECFCs were enhanced after pravastatin treatment, and AKT- and eNOS-phosphorylation were augmented. Further, expression levels of HO-1, VEGF-A and PlGF were increased, whereas expression levels of sFlt-1 and Eng were decreased. Pravastatin induced effects were reversible by the addition of mevalonate. Pravastatin induces beneficial effects on ECFC function, angiogenic signaling and protein expression. These effects may contribute to understand the pleiotropic function of statins as well as to provide a promising option to improve ECFCs' condition in cell therapy in order to ameliorate endothelial dysfunction.