The emerging evidence for vitamin D–mediated regulation of apolipoprotein A-I synthesis

Ischemic heart disease and cerebrovascular ischemia are leading causes of mortality in industrialized countries. The pathogenesis of these diseases involves the formation of atherosclerotic plaques with eventual rupture and superimposed thrombosis. This process is inhibited by high-density lipoprotein (HDL), the main protein component of which is apolipoprotein A-I (apo A-I). Vitamin D3 is a hormone produced by sun-exposed skin but is acquired also in the diet. The Framingham Offspring Study and the Third National Health and Nutritional Examination Survey showed a link between vitamin D3 intake and cardiovascular risk factors. The link between 25-hydroxyvitamin D3 and HDL cholesterol (HDLc) and apo A-I is not as clear. Studies in vitamin D receptor knockout mice demonstrated higher HDLc and hepatic apo A-I messenger RNA expression relative to wild type. Experiments in cultured hepatocytes supported these observations. Human studies evaluating the relationship between vitamin D3 and apo A-I and HDLc have yielded conflicting results, but most suggest a positive link between increasing vitamin D3 levels and plasma apo A-I and HDLc. The purpose of this review is to examine the evidence linking vitamin D status and cardiovascular disease, to determine if there is a relationship between vitamin D levels and development of an atherogenic lipid profile. Our objectives are to determine if plasma vitamin D levels correlate with plasma HDLc and apo A-I and, if so, offer speculation as to how apo A-I in the context of high vitamin D levels provides enhanced atheroprotection.