Vascular calcification is a common feature in advanced
atherosclerosis and also a predictor of future cardiovascular events such as
unstable angina and
myocardial infarction, especially in diabetes. There is a growing body of evidence that
advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate in diabetes, exist within atherosclerotic lesions, thereby being implicated in the pathogenesis of accelerated
atherosclerosis in diabetes. Indeed, we have previously shown that AGE - their receptor (RAGE) interaction could induce angiogenesis through autocrine production of
vascular endothelial growth factor, suggesting its role for plaque formation and enlargement in diabetes. Furthermore, we have found that AGEs have the ability to induce the osteoblatic differentiation of pericytes, thus contributing to the development of
vascular calcification as well. These observations suggest that the inhibition of AGE formation or blockade of the downstream signaling of RAGE may be a novel therapeutic target for the inhibition of
vascular calcification in diabetic
atherosclerosis. Since we, along with others, have shown that
nifedipine inhibits glycation of
low-density lipoprotein in vitro and blocks the AGE-induced RAGE expression in endothelial cells through its anti-oxidative properties,
nifedipine could inhibit
vascular calcification by blocking the AGE formation or the downstream signaling in diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis. Does
nifedipine treatment slow down the progression of coronary calcification in diabetic patients? If the answer is yes, is this beneficial effect of
nifedipine superior to that of other DHPs with equihypotensive properties? Does
nifedipine treatment decrease expression levels of AGEs and RAGE in diabetic
atherosclerosis? Is the unique effect of
nifedipine on
vascular calcification correlated with its AGE or RAGE-suppressing properties? These prospective studies will provide further valuable information whether
nifedipine could prevent
vascular calcification in diabetic
atherosclerosis by blockade the AGE-RAGE signaling in vascular wall cells.