Platelets induce differentiation of human CD34 ⁺ progenitor cells into foam cells and endothelial cells

Abstract

Recruitment of human CD34+ progenitor cells toward vascular lesions and differentiation into vascular cells has been regarded as a critical initial step in atherosclerosis. Previously we found that adherent platelets represent potential mediators of progenitor cell homing besides their role in thrombus formation. On the other hand, foam cell formation represents a key process in atherosclerotic plaque formation. To investigate whether platelets are involved in progenitor cell recruitment and differentiation into endothelial cells and foam cells, we examined the interactions of platelets and CD34+ progenitor cells. Cocultivation experiments showed that human platelets recruit CD34+ progenitor cells via the specific adhesion receptors P-selectin/PSGL-1 and beta1- and beta2-integrins. Furthermore, platelets were found to induce differentiation of CD34+ progenitor cells into mature foam cells and endothelial cells. Platelet-induced foam cell generation could be prevented partially by HMG coenzyme A reductase inhibitors via reduction of matrix metalloproteinase-9 (MMP-9) secretion. Finally, agonists of peroxisome proliferator-activated receptor-alpha and -gamma attenuated platelet-induced foam cell generation and production of MMP-9. The present study describes a potentially important mechanism of platelet-induced foam cell formation and generation of endothelium in atherogenesis and atheroprogression. The understanding and modulation of these mechanisms may offer new treatment strategies for patients at high risk for atherosclerotic diseases.

The degree of premature hair graying as an independent risk marker for coronary artery disease: a predictor of biological age rather than chronological age

“…After firstly defined by Asaraha et al (21), we have gained more knowledge about their source, roles, levels and functionality. CVRFs, like aging, DM, hyperlipidemia and smoking, affect the EPC count and act destructively (22)(23)(24)(25)(26)(27)(28)(29). Recently, these effects are emphasized for the development of atherosclerosis.…”

Platelet-vessel wall interactions in atherosclerotic disease

“…Therefore it seems likely that platelets are capable of modifying progenitor cell biology. Indeed, when exposed to isolatedp latelets murine embryonalEPCsorhumanCD34 + stem cellscan differentiate towards mature endothelial cells ( 54,60). Furthermore, platelets seem to enhancethe biologicalpower of EPCs by increasingtheir chemotaxis andmigratorypotential (54).…”

“…Recently, we characterized anotherfate, which progenitor cellsundergoafterincubation with platelets. CD34 + humans tem cells exposed to platelets underdistinct conditions in vitro resulted in plateletuptake by the progenitor cellsand finallyinthe development of foam cell-like cells (60)(61)(62). Therefore alsoc ontraproductive effects arem ediatedb yp latelet-EPCi nteraction, which canb ec ontrolled in vitro by the application of statins (60,63).…”

“…CD34 + humans tem cells exposed to platelets underdistinct conditions in vitro resulted in plateletuptake by the progenitor cellsand finallyinthe development of foam cell-like cells (60)(61)(62). Therefore alsoc ontraproductive effects arem ediatedb yp latelet-EPCi nteraction, which canb ec ontrolled in vitro by the application of statins (60,63). Amajormolecule involved in platelet-mediated effects on progenitor cellsseems to be the chemokine SDF-1, as platelet-derivedSDF-1 regulates recruitment, proliferation anddifferentiation of progenitor cells, a mechanismmostlikelycontributing to vascularrepair andregeneration of ischemicm yocardium (23,24,64).…”

Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression

“…To quantify the P-selectin (platelet adhesion molecule) expression, platelets were isolated from human blood by centrifugation method as described in literature [15]. Ethanol in C18-DOM was evaporated in an automatic environmental NMR spectroscopy.…”