3-(2-4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3h)-quinazolinone and Cardiovascular-Diseases

Vascular senescence, which is closely related to epigenetic regulation, is an early pathological condition in cardiovascular diseases including atherosclerosis. Inhibition of S-adenosylhomocysteine hydrolase (SAHH) and the consequent increase of S-adenosylhomocysteine (SAH), a potent inhibitor of DNA methyltransferase, has been associated with an elevated risk of cardiovascular diseases. This study aimed to investigate whether the inhibition of SAHH accelerates vascular senescence and the development of atherosclerosis.. The case-control study related to vascular aging showed that increased levels of plasma SAH were positively associated with the risk of vascular aging, with an odds ratio (OR) of 3.90 (95% CI, 1.17-13.02). Elevated pulse wave velocity, impaired endothelium-dependent relaxation response, and increased senescence-associated β-galactosidase staining were observed in the artery of SAHH. SAHH inhibition epigenetically upregulates Drp1 expression through repressing DNA methylation in endothelial cells, leading to vascular senescence and atherosclerosis. These results identify SAHH or SAH as a potential therapeutic target for vascular senescence and cardiovascular diseases.

Topics: Adenosylhomocysteinase; Animals; Atherosclerosis; Cardiovascular Diseases; Case-Control Studies; Endothelial Cells; Epigenesis, Genetic; Mice; Mitochondrial Dynamics; Pulse Wave Analysis; S-Adenosylhomocysteine