Abstract

In addition to a centrally‐mediated influence on blood pressure, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to hypertension and atherosclerotic plaque development. These functions are characteristics of CD16‐positive monocytes implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of CD16‐positive monocytes in healthy men and women ranging in age from 20‐59 years. Circulating numbers of CD14+16++ monocytes, which preferentially migrate into nascent plaques, correlated with plasma leptin in men (R = 0.68, P = 0.01), but not women. In vitro, exogenous leptin increased percentages of CD14+16++ monocytes in cultures of male cells and reduced them in cultures of female cells (P=0.03 for leptin*sex interaction). For all subjects, circulating CD14+16++ cell counts correlated with systolic pressure (R=0.45, P=0.02) and carotid intima‐media thickness (R=0.36, P=0.04). There were no sex‐related differences in total expression of leptin receptors, measured by flow cytometry, or in relative expression of different isoforms of the receptor, measured by western blots. These results support the concept that leptin promotes the development of an atherogenic monocyte phenotype and has a stronger influence in men than in women.Grant Funding Source: Supported by NIH grant HL093663

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