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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2530.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Increased Ratio of CD31⁺/CD42^– Microparticles to Endothelial Progenitors as a Novel Marker of Atherosclerosis in Hypercholesterolemia

Matteo Pirro; Giuseppe Schillaci; Rita Paltriccia; Francesco Bagaglia; Cinzia Menecali; Massimo R. Mannarino; Marusca Capanni; Andrea Velardi; Elmo Mannarino

From the Unit of Internal Medicine, Angiology, and Arteriosclerosis (M.P., G.S., R.P., F.B., C.M., M.R.M., E.M.) and the Division of Hematology and Clinical Immunology (M.C., A.V.), Department of Clinical and Experimental Medicine, University of Perugia, Italy.

Correspondence to Matteo Pirro, MD, PhD, Medicina Interna, Angiologia e Malattie da Arteriosclerosi, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, 06123 Perugia, Italia. E-mail mpirro{at}unipg.it

Objectives— Atherosclerosis may be caused by increased endothelial damage and by a consumptive loss of endothelial repair capacity by endothelial progenitors. Arterial stiffness is a reliable marker of atherosclerosis and a positive correlate of endothelial damage. We investigated whether an increased ratio of CD31⁺/CD42^– microparticles to endothelial progenitors, a possible indicator of endothelial damage and impaired endothelium reparation, may contribute to aortic stiffness in hypercholesterolemia. We also studied the in vitro effect of microparticles from hypercholesterolemic patients on endothelial progenitor survival.

Methods and Results— Circulating CD31⁺/CD42^– microparticles, endothelial progenitors, and aortic pulse wave velocity (aPWV), a measure of aortic stiffness, were measured in 50 patients with never-treated hypercholesterolemia and 50 normocholesterolemic controls. Hypercholesterolemic patients had more circulating CD31⁺/CD42^– microparticles, less endothelial progenitors, and a stiffer aorta than controls. aPWV was associated with CD31⁺/CD42^– microparticles (r=0.61; P<0.001), endothelial progenitors (r=–0.45, P<0.001), and with cholesterol levels (r=0.51; P<0.001). High plasma cholesterol and a high ratio of CD31⁺/CD42^– microparticles to endothelial progenitors independently predicted an increased aPWV. Microparticles from hypercholesterolemic patients caused a significant endothelial progenitor loss in vitro.

Conclusions— Hypercholesterolemia-related aortic stiffness is promoted by plasma cholesterol directly, increased endothelial damage, and reduced endothelium repair capacity by endothelial progenitors.

Atherosclerosis may be caused by increased endothelial damage and loss of endothelial repair by circulating progenitors. We found that hypercholesterolemic patients have a stiffer aorta, more CD31⁺/CD42^– microparticles, and less endothelial progenitors than normocholesterolemic subjects. An increased ratio of CD31⁺/CD42^– microparticles to endothelial progenitors independently predicted increased aortic stiffness.

Key Words: arterial stiffness • endothelial progenitor cells • hypercholesterolemia • microparticles

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