Influence of Fe(II) and Fe(III) on the expression of genes related to cholesterol- and fatty acid metabolism in human vascular smooth muscle cells

Abstract

Iron is the major alloy component for a large variety of cardiovascular devices such as stents. In recent studies it has been shown that biodegradable iron or iron based stents exhibit good mechanical features with no pronounced neointimal proliferation. Whole genome gene profiling using DNA chip technology revealed that genes involved in cholesterol and fatty acid metabolism (low-density lipoprotein receptor, LDL-R; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (HMGCS1) and fatty acid desaturase 1 (FADS1) are up-regulated after exposure of vascular smooth muscle cells with soluble ferrous iron. To analyze the effects of iron on these genes in detail we co-incubated human vascular smooth muscle cells for 12 and 24 h with different concentrations of ferrous (soluble iron(II)-gluconate) and ferric iron (soluble iron(III)-chloride), Ferrlecit, a commercially available drug (ferric iron-gluconate complex) and solid iron coils. The expression of LDL-R, HMGCS1 and FADS1 was analyzed using TaqMan Real-time PCR. After 24 h, all forms of iron led to a significant up-regulation of the examined genes. At high concentrations the expression rates declined, probably as a result of reduced metabolic activity. The most prominent effects were observed after co-incubation with Ferrlecit, probably caused by an increased bioavailability of the iron gluconate complex. We postulate that both, bi- and trivalent forms of iron induce the expression of LDL-R, HMGCS1 and FADS1 by generation of highly reactive oxygen species. Further animal experiments using tissues from iron-stented vessels may lead to a more profound insight into iron induced expression of cholesterol- and fatty acid metabolism related genes.