Identifying and preventing modifiable risk factors for cardiovascular disease is very important. Vascular calcification has been studied clinically as an asymptomatic preclinical marker of atherosclerosis and a risk factor for cardio-cerebrovascular disease. It is known that higher homocysteine levels are associated with calcified plaques and the higher the homocysteine level, the higher the prevalence and progression of vascular calcification. Homocysteine is a byproduct of methionine metabolism and is generally maintained at a physiological level. Moreover, it may increase if the patient has a genetic deficiency of metabolic enzymes, nutritional deficiencies of related cofactors (vitamins), chronic diseases, or a poor lifestyle. Homocysteine is an oxidative stress factor that can lead to calcified plaques and trigger vascular inflammation. Hyperhomocysteinemia causes endothelial dysfunction, transdifferentiation of vascular smooth muscle cells, and the induction of apoptosis. As a result of transdifferentiation and cell apoptosis, hydroxyapatite accumulates in the walls of blood vessels. Several studies have reported on the mechanisms of multiple cellular signaling pathways that cause inflammation and calcification in blood vessels. Therefore, in this review, we take a closer look at understanding the clinical consequences of hyperhomocysteinemia and apply clinical approaches to reduce its prevalence.

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