Endothelial dysfunction is considered an early marker of atherosclerosis. Herein, we address the molecular mechanisms affecting endothelium remodeling in disease. Vascular calcification is highly prevalent in patients with ischemic cardiovascular disease, cerebrovascular disorder, and renal failure, being a common feature in aging, diabetes, dyslipidemia, abnormal valve biomechanics, end-stage renal disease and atherosclerosis, a major cause of mortality and morbidity. Oxidative stress promotes calcification of vascular smooth muscle cells (SMC) by increasing osteogenic transcription factors expression and activity in atherosclerotic plaques. Various markers of osteogenic differentiation are expressed by SMC in calcified atherosclerotic lesions. Interestingly, decreased levels of some bone factors and microRNAs accelerate vascular calcification and injured tissue regeneration. Another key player in endothelial remodeling is amino acids metabolism. Branched-chain amino acids are catabolized in several nonhepatic tissues including cardiac muscle. Immune activation and inflammation in cardiovascular disease patients associate with higher phenylalanine/tyrosine ratios. Understanding the whole process that underlies endothelium dysfunction is of paramount importance for the development of new therapeutic approaches.
Keywords: alkaline phosphatase; amino acids; atherosclerosis; bone factors; epigenetic; nitric oxide; vascular calcification.
© 2019 Wiley Periodicals, Inc.