Copper and homocysteine in cardiovascular diseases.
High blood copper (Cu) and homocysteine (Hcy) concentrations have been independently reported as risk factors for cardiovascular diseases. When they are simultaneously measured, a concomitant increase in both parameters in association with vascular dysfunction has been observed. Cu chelator penicillamine can significantly diminish the inhibitory effect of Hcy on endothelial function, which has led to the interpretation that Cu mediates the deleterious effect of Hcy. However, Cu itself has been shown to be beneficial to the cardiovascular system. In particular, Cu promotion of angiogenesis has been well documented. Cu stimulates endothelial cell proliferation and differentiation and promotes microtubule formation in cultured saphenous veins. High levels of Hcy do not affect the process of microtubule formation, but the combination of Cu and Hcy leads to a significant inhibitory effect. Under other conditions, Cu does not affect, but Hcy inhibits, the endothelium-dependent relaxation of blood vessels and the combination of both augments the inhibition. Why does Cu produce adverse effects when it co-exists with Hcy? Cu forms complexes with Hcy and the Cu-Hcy complexes possess a deleterious potential due to their redox properties. Cu chelation can remove Cu from the Cu-Hcy complexes, but leaves behind high levels of Hcy and produces Cu deficiency. An alternative approach should focus on the reduction of Hcy, but maintenance of Cu, making detrimental Cu beneficial. A comprehensive understanding of Cu speciation and a development of selective modulation of Cu coordination to Cu-binding molecules to avoid Cu-Hcy complex formation would effectively improve the condition of cardiovascular disease.
Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. yjkang01@louisville.edu
Y James
YJ
Kang
D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism*; D003300:Copper / Q000097:blood / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans
D006710:Homocysteine; D003300:Copper