Platelets of Healthy Origins Promote Functional Improvement of Atherosclerotic Endothelial Progenitor Cells

Abstract

The purpose was to evaluate the effect of platelets on functional properties of late endothelial progenitor cells (EPCs), in the direct co-culture conditions, and to investigate the involved mediators, in experimental induced atherosclerosis. The late EPCs obtained from two animal groups, hypertensive-hyperlipidemic (HH) and control (C) hamsters, named late EPCs-HH and late EPCs-C, were co-incubated with or without platelets isolated from both groups. Our results have showed that exposure to platelets from control animals: (i) promoted the late EPCs-C capacity to form colonies and capillary-like structures, and also to proliferate and migrate; (ii) improved the functional properties of late EPCs-HH; (iii) strengthened the direct binding EPCs-platelets; (iv) increased SDF-1α,VEGF, PDGF, and reduced CD40L, IL-1β,-6,-8 levels; and (v) enhanced miR-223 and IGF-1R expressions. Platelets from HH group diminished functional abilities for both EPC types and had opposite effects on these pro-angiogenic and pro-inflammatory molecules. Furthermore, testing the direct effect of miR-223 and IGF-1R on late EPCs disclosed that these molecular factors improve late EPC functional properties in atherosclerosis in terms of stimulation of the proliferation and migration abilities. In conclusion, in vitro exposure to platelets of healthy origins had a positive effect on functional properties of atherosclerotic late EPCs. The most likely candidates mediating EPC-platelet interaction can be SDF-1α, VEGF, CD40L, PDGF, IL-1β,-6,-8, miR-223, and IGF-1R. The current study brings evidences that the presence of healthy origin platelets is of utmost importance on functional improvement of EPCs in atherosclerosis.

Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells

“…The realization of this study was also based on our recent experimental results showing that platelets of healthy origins support functional improvement of atherosclerotic EPCs [50].…”

Hypertension Associated With Hyperlipidemia Induced Different MicroRNA Expression Profiles in Plasma, Platelets, and Platelet-Derived Microvesicles; Effects of Endothelial Progenitor Cell Therapy

“…The experiments were carried out on plasma, platelets and PMVs, obtained from the blood of Golden Syrian hamsters (3 months old, n = 30) divided in three equal groups: (1) C (control hamsters), age-matched normal healthy animals which received an ordinary hamster diet; (2) HH (simultaneously hypertensive-hyperlipidemic hamsters), fed with ordinary diet enriched with 3% cholesterol, 15% butter and 8% NaCl, for 4 months; (3) HH-EPCs (HH hamsters treated with EPCs), animals that received 1 x 10 5 EPCs (isolated from C group) in a volume of 300 μl, in a dose per month, via the retro-orbital venous sinus injection, during 4 months of diet specific to the HH hamster, to prevent atherosclerosis process; (27–29, 49, 50) and (19, 30, 31). At the end of the experiment, the hamsters were sacrificed for biochemical assays.…”

“…The use of animals in experiments and the procedures necessary to carry out the research study have approved by the Ethics Committees from Institute of Cellular Biology and Pathology “Nicolae Simionescu,” and they have been realized in agreement with National, European and International legislation on the use of experimental animals in biomedical research (29, 50).…”

“…Platelets were separated according to the method reported by Alexandru et al (27, 28, 50). Briefly, the hamsters were slightly anesthetized with 2% isoflurane in oxygen (2.4 l/min), and venous blood was collected from the retro-orbital venous sinus (~1.5 ml per hamster), in ACD buffer (2.73% citric acid, 4.48% trisodium citrate, and 2% glucose) and centrifuged at 400 x g for 10 min to obtain the PRP.…”

Autophagy-Sirtuin1(SIRT1) Modulated The Endothelial Progenitor Cells (EPCs) Proliferation and Migration Via wnt/β-Catenin/GSK3β Signaling Pathway and Alleviated The Coronary Atherosclerosis (CAS) in Mice

“…Fundamentally, EPC levels in uenced the coronary artery endothelial functions and neovascularization [2]. EPCs were noticed in the 1990s and due to its potential vasculogenesis and endothelial monolayer regeneration [3], were extensively investigated in coronary heart diseases thereafter both in clinical and experimental elds [4][5][6][7]. In CAS patients, decreased counts of EPCs are associated with the oxidised low-density lipoprotein (oxLDL) levels, a clinically signi cant index of CAS diagnosis [2].…”