Leptin enhances the calcification of vascular cells - Artery wall as a target of leptin

Leptin, the product of the ob gene, regulates food intake, energy expenditu re, and other physiological functions of the peripheral tissues. Leptin rec eptors have been identified in the hypothalamus and in extrahypothalamic ti ssues. Increased circulating leptin levels have been correlated with cardio vascular disease, obesity. aging. infection with bacterial lipopolysacchari de, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-re lated vascular disease. In addition, the differentiation of marrow osteopro genitor cells is regulated by leptin, Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested th e effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro . When treated with leptin, these calcifying vascular cells had a significa nt 5- to 10-fold increase in alkaline phosphatase activity, a marker of ost eogenic differentiation of osteoblastic cells. Prolonged treatment with lep tin enhanced the calcification of these cells, further supporting the pro-o steogenic differentiation effects of leptin. Furthermore, the presence of t he leptin receptor on calcifying vascular cells was demonstrated using reve rse transcriptase polymerase chain reaction, immunocytochemistry and Wester n blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial ce lls, and the expression of leptin by artery wall cells and atherosclerotic Lesions in mice. Taken together, these results suggest that leptin regulate s the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.