Carnosine attenuates vascular smooth muscle cells calcification through mTOR signaling pathway

Abstract

Vascular calcification is increasingly afflicting the aging population, driven by the dysmetabolic milieus of diabetes, chronic kidney disease (CKD), and arterial stiffness. 1-4 Although it has always been considered as an independent predictive factor of cardiovascular events and associated morbidity, the precise relationship between aging and vascular calcification is not well understood. Aging has been demonstrated as a complex multifactorial process, converse to the previous models built on single factors. 5 Therefore, we focused on carnosine (β-alanyl-l-histidine), a naturally occurring dipeptide that is abundant in the brain tissue and muscles. 6 It performs multiple biological functions, including anti-inflammation, anti-oxidation, chelating metal ions, and anti-glycosylation. 6-8 As previously mentioned, the complexity of the aging process has superseded previous constructs based on single factors. Recent reports show that carnosine may improve the treatment outcome of aging-related diseases, such as atherosclerosis, type 2 diabetes, and Alzheimer's disease. 9-11 Studies show that carnosine suppresses cell senescence in cultured human fibroblasts 12 and delays aging in senescence-accelerated mice and drosophila. 13-15 In addition, some in vitro/in vivo studies using human and animal models show that synthesis of carnosine decreases with age. 15 Recent research reports that carnosine can alleviate aging-related vascular diseases, such as atherosclerosis and type 2 diabetes. Vascular calcification is a complication that also occurs during aging,

Integrated proteomic and metabolomic profile analyses of cardiac valves revealed molecular mechanisms and targets in calcific aortic valve disease

“…Carnosine is a decisive factor in the formation of atherosclerotic lesions, and it can repress atherogenesis by promoting the removal of aldehydes derived from oxidized lipids ( 33 ). Based on a calcification model of vascular smooth muscle cells (VSMCs), Huang et al ( 34 ) reveals that carnosine can attenuate calcium deposition in a dose-dependent way by reducing expression of osteogenesis-related proteins RUNX2 and BMP2. Compared with normal controls, plasma choline levels are significantly increased in patients with AS, as well as in patients whose aortic valves had neovascularization, calcification, metaplastic ossification, and more severe tissue remodeling.…”

Senescence in Vascular Smooth Muscle Cells and Atherosclerosis

“…Downregulation of miR-542-3p in VSMCs plays an important role in the osteogenic transformation of these cells in aging rats and is achieved by targeting BMP-7 ( 68 ). Recently, myostatin was reported to reduce the expression of Runx-2 and BMP-2 in rat VSMCs, operating through the mammalian target of rapamycin (mTOR) signaling pathway and thereby attenuating VSMCs calcification ( 69 ).…”

Vascular Calcification: In Vitro Models under the Magnifying Glass

“…Carnosine is a dipeptide with antioxidant, anti-inflammatory, and anti-senescence properties [ 77 , 78 ]. Yi and colleagues showed that carnosine inhibited Pi-induced VSMCs calcification by reducing Ca 2+ levels and ALP activity and suppressing the expression of the osteogenic markers Runx2 and BMP-2 [ 79 ]. Carnosine also inhibited the mTOR pathway [ 80 ], which plays a crucial role in the osteoblastic differentiation of VSMCs [ 96 ].…”