Metoprolol Protects Against Arginine Vasopressin-Induced Cellular Senescence in H9C2 Cardiomyocytes by Regulating the Sirt1/p53/p21 Axis

Abstract

Cardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a β1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated β-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.

Visfatin and Subclinical Atherosclerosis in Type 2 Diabetes: Impact of Cardiovascular Drugs

“…There is limited evidence to suggest that β-blockers affect visfatin levels in the human body. Treatment with metoprolol ameliorated decreased intracellular visfatin activity in cardiomyocytes [ 33 ], while Skoczylas et al observed significant reductions in plasma visfatin levels compared to baseline values after 6 weeks of treatment with bisoprolol in patients with essential hypertension [ 19 ]. Contrary to previous studies and our expectations, we found that β-blocker users had higher levels of visfatin.…”

Metabolic Changes in Cardiac Aging

“…Because decreased cardiac -AR reactivity leads to decreased cardiac function and muscle strength reserve, treatments to restore -AR reactivity (such as beta blockers) can improve cardiac function in older patients [ 79 ]. To reduce sympathetic nerve activity, studies have found that metoprolol can down-regulate arginine vasopressin (AVP) induced acetylated p53 and p21 expression, so metoprolol can protect AVP induced cardiomyocyte senescence [ 80 ].…”

The “brain-heart-gut” axis and novel mechanisms of future cardiovascular disease

“…It's really a hot topic in life science and biomedicine. Here are summarized tables on major studies of axis and eCVD or fCVD in cardiovascular journals (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) and non-cardiovascular journals (25-42) (Table 1 & Table 2). However, exception of several reviews on "Brain-Gut-Bone Marrow Axis" (Santisteban MM, et al 2016) (43) and "Heart-Brain Axis" (Tahsili-Fahadan P & Geocadin RG, 2017) (44), which involved in cardiovascular risk, the mechanisms and treatment, most of these studies, and reviews or comments just only involved in targeting these "branch axis" of eCVD (atherosclerosis, hypertension, and others), for example, the CCL2-CCR2 axis (Georgakis MK, et al 2022;Crea F, 2022) (45,46).…”