Abstract
Vascular calcification is a pathophysiological process that is associated with coronary atherosclerosis, and is a prognostic marker of cardiovascular morbidity and mortality. The process of arterial wall calcification is triggered and accompanied by pro-osteogenic phenotypical modifications of resident smooth muscle cells (SMC). Vitamin C (ascorbic acid) is an essential nutrient required to support the production of extracellular matrix components and maintain healthy connective tissue. In this study we investigated the effects of ascorbic acid on cultured human aortic SMC calcification process in vitro. Our results demonstrate that supplementation of SMC cultures with ascorbic acid significantly decreases calcium accumulation in SMC-produced and -deposited extracellular matrix. These effects were accompanied by a reduction in cell-associated alkaline phosphatase activity. Significantly, treatment of cultured SMC with HMG-CoA reductase inhibitors, simvastatin and mevastatin, resulted in increased calcium accumulation in cultured SMC. These effects were blocked by ascorbic acid. The effects of ascorbic acid supplementation on pro-osteogenic modification were compared in different cell types. Analysis of the expression of osteogenic markers in cultured human aortic SMC, human dermal fibroblasts and immortalized human osteoblasts (hFOB) revealed cell type-specific responses to ascorbate supplementation. We conclude that ascorbic acid supplementation can actively and beneficially interfere with the process of arterial wall calcification, with potential implications for human health.