Gender Differences in Circulating Endothelial Progenitor Cell Colony-Forming Capacity and Migratory Activity in Middle-Aged Adults

Abstract

Middle-aged women have a lower prevalence and incidence of cardiovascular events than men. The mechanisms responsible for this sex-specific difference are unclear. Numerical and functional impairment of bone marrow-derived circulating endothelial progenitor cells (EPCs) is associated with increased cardio-and cerebrovascular morbidity and mortality. It is currently unknown whether there are sex-related differences in EPC number and function in middle-aged adults. We tested the hypothesis that EPCs isolated from middle-aged women demonstrate greater colony forming capacity and migratory activity compared with men of similar age. Peripheral blood samples were collected from 50 sedentary adults; 25 men (age: 59±1 yr) and 25 women (58±1 yr). Mononuclear cells were isolated, preplated for 2 days and nonadherent cells were further cultured for 7 days to determine EPC colony forming units. Migratory activity of EPCs was determined using a modified Boyden chamber. The number of EPC colony forming units was significantly higher (∼150%) in samples collected from women (16±3) compared with men (7±1). In addition, EPC migration (relative fluorescent units) was ∼40% greater in women (729±74) versus men (530±67). These results demonstrate that EPC colony forming capacity and migratory activity are higher in middle-aged women compared with men. Keywordsendothelial progenitor cells; colony-forming units; migration Cardiovascular disease is the most frequent cause of death in both men and women. However, between the ages of 45 and 65 years, the prevalence of coronary heart disease and the incidence of myocardial infarction and stroke is ∼50% higher in men compared with women. The mechanisms responsible for this sex-related disparity are currently unclear. Interestingly, there are no apparent sex differences in the incidence and prevalence of traditional cardiovascular disease risk factors such as hypertension, obesity, tobacco use, hyperlipidemia, diabetes, or sedentary lifestyle in middle-aged adults 1 . Clinical interest in bone marrow-derived circulating endothelial progenitor cells as a novel vascular risk factor has increased due to their importance in vascular repair and noted inverse relation with endothelial dysfunction as well as cardiovascular and cerebrovascular disease 2-4 . Indeed, reduced EPC number and migratory activity have been linked to atherosclerotic disease progression and cardiovascular events This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptAm J Cardiol. Author manuscript; available in PMC 2008 January 1. NIH-PA Author ManuscriptNIH-PA Author Man...

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