Published online before print September 12, 2002, doi: 10.1161/01.RES.0000036607.05037.DA
© 2002 American Heart Association, Inc.
Molecular Medicine |
High-Density Lipoprotein Regulates Calcification of Vascular Cells
From the Departments of Medicine (F.P., B.B., J.H., Y.T., L.L.D.) and Physiology (L.L.D.), University of California, Los Angeles.
Correspondence to Farhad Parhami, PhD, Associate Professor of Medicine, UCLA Division of Cardiology, CHS 47-123, 10833 Le Conte Ave, Los Angeles, CA 90095. E-mail fparhami{at}mednet.ucla.edu
Accumulating evidence has suggested the protective role of HDL in cardiovascular disease processes. Calcification is a common feature of atherosclerotic lesions and contributes to cardiovascular complications due to the loss of aortic resilience and function. Recent studies have suggested that vascular calcification shares several features with skeletal bone formation at the cellular and molecular levels. These include the presence of osteoblast-like calcifying vascular cells in the artery wall that undergo osteoblastic differentiation and calcification in vitro. We hypothesized that HDL may also protect against vascular calcification by regulating the osteogenic activity of these calcifying vascular cells. When treated with HDL, alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells, was significantly reduced in those cells. Prolonged treatment with HDL also inhibited calcification of these cells, further supporting the antiosteogenic differentiation property of HDL when applied to vascular cells. Furthermore, HDL inhibited the osteogenic activity that was induced by inflammatory cytokines interleukin (IL)-1ß and IL-6 as well as by minimally oxidized LDL. HDL also partially inhibited the IL-6-induced activation of signal transducer and activator of transcription 3 in calcifying vascular cells, suggesting that HDL may inhibit cytokine-induced signal transduction pathways. The inhibitory effects of HDL were mimicked by lipids extracted from HDL but not by HDL-associated apolipoproteins or reconstituted HDL. Furthermore, oxidation of HDL rendered it pro-osteogenic. Taken together, these results suggest that HDL regulates the osteoblastic differentiation and calcification of vascular cells and that vascular calcification may be another target of HDL action in the artery wall.
Key Words: vascular calcification • calcifying vascular cells • high-density lipoproteins • cytokines
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