Role of homocysteine in aortic calcification and osteogenic cell differentiation

Abstract

Background: The role of homocysteine in atherosclerosis is unclear.We examined the relationship between plasma homocysteine and infrarenal aortic calcification, the presence of homocysteine in human atheroma and the influence of homocysteine on osteogenic differentiation in vitro.

Methods and results: In 194 patients with symptomatic peripheral artery disease or abdominal aortic aneurysm, fasting plasma total homocysteine was independently associated with the severity of infrarenal aortic calcification measured by Computer Tomography Angiography (odds ratio 1.91, 95% confidence interval 1.17–3.21 for calcification ≥median). Homocysteine was identified in all 60 atheroma biopsies from 16 patients undergoing endarterectomy, and concentrations were significantly greater in the calcified biopsies (p = 0.003). In vitro studies demonstrated that 100 mol/L homocysteine doubled the calcium deposition by mesenchymal stem cells during 16 days incubation in osteogenic medium (74±4 compared to 42±5g calcium/well without homocysteine, p < 0.001). Homocysteine also stimulated monocytic THP1 cells to promote aortic smooth muscle cell calcification as evidenced by significant higher calcium deposition and alkaline phosphatase activity compared to incubation without homocysteine (p≤0.05).

Conclusions: Homocysteine plays an important role in vascular calcification via multiple mechanisms. The presence of homocysteine in atheroma and its ability to enhance osteogenic cell differentiation may partly explain the association of homocysteine with atherosclerotic events.