1,12-cyclic-apelin-12 counters vascular smooth muscle cell proliferation and atherosclerosis through inhibiting...

Atherosclerosis is a chronic vascular disease driven in part by vascular smooth muscle cell (VSMC) phenotypic switching, migration, and excessive proliferation. In our previous work, Apelin-13 was shown to promote aerobic glycolysis and thereby stimulate VSMC proliferation. Here, we developed a novel 1,12-cyclic Apelin-12 peptide (c-Apelin-12) by cyclizing the N- and C-termini of Apelin-12 through an amide bond. We found that c-Apelin-12 effectively attenuated Apelin-13-induced VSMC proliferation, reduced mitochondrial injury, and suppressed aerobic glycolysis. In vivo, c-Apelin-12 treatment significantly decreased atherosclerotic plaque formation and reduced the expression of proliferation-associated markers and key glycolytic enzymes. These findings indicated that c-Apelin-12 mitigated Apelin-13-induced VSMC proliferation and atherosclerotic progression by alleviating aerobic glycolysis. c-Apelin-12 may therefore represent a promising therapeutic candidate for atherosclerosis.