No abstract

Calcific aortic valve stenosis (CAVS) is the most prevalent heart valvular disease worldwide and a slowly progressive disorder characterized by thickening of the aortic valve, calcification, and subsequent heart failure. Valvular calcification is an active cell regulation process in which valvular interstitial cells involve phenotypic conversion into osteoblasts/chondrocytes-like cells. The underlying pathophysiology is complicated, and there have been no pharmacological treatments for CAVS to date. Recent studies have suggested that an increase in oxidative stress is the major trigger of CAVS, and natural antioxidants could ameliorate the detrimental effects of reactive oxygen species in the pathogenesis of CAVS. It is imperative to review the current findings regarding the role of natural antioxidants in CAVS, as they can be a promising therapeutic approach for managing CAVS, a disorder currently without effective treatment. This review summarizes the current findings on molecular mechanisms associated with oxidative stress in the development of valvular calcification and discusses the protective roles of natural antioxidants in the prevention and treatment of CAVS.

Nano plastics (NPs) have been a significant threat to human health and are known to cause premature endothelial senescence. Endothelial senescence is considered one of the primary risk factors contributing to numerous cardiovascular disorders. Recent studies have suggested that inhibition of sodium glucose co-transporter (SGLT2) ameliorates endothelial senescence and dysfunction. Therefore, our study intends to explore the role of SGLT2 in NPs-induced endothelial senescence and dysfunction. Porcine coronary artery and its endothelial cells were treated with NPs in the presence or absence of Enavogliflozin (ENA), a SGLT2 inhibitor and then SGLTs expression, senescence markers and vascular function were evaluated. NPs significantly up-regulated SGLT2 and ENA significantly decreased NPs-induced senescence-associated-β‐gal activity, cell‐cycle arrest, and senescence markers p53 and p21 suggesting that inhibition of SGLT2 prevents NPs-induced endothelial senescence. In addition, ENA decreased the formation of reactive oxygen species with the downregulation of Nox2, and p22phox. Furthermore, SGLT2 inhibition also up regulated the endothelial nitric oxide synthase expression along with improving vascular function. In conclusion, premature endothelial senescence by NPs is, at least in part, associated with SGLT2 and it could be a potential therapeutic target for preventing and/or treating environmental pollutants-induced cardiovascular disorders mediated by endothelial senescence and dysfunction.

Background: Nanoplastics (NPs) are now widely acknowledged as a vital part of environmental pollution. However, the effects of NPs on the cardiovascular system are not well understood. We previously reported that NPs induce premature endothelial senescence and dysfunction via a redox-sensitive signaling pathway. Increasing evidence has shown that SGLT2 inhibitors (gliflozins) exhibit protective effects against the development of major cardiovascular diseases. Objective: This study aimed to investigate the role of SGLT2 on NPs-induced premature endothelial senescence and dysfunction, and, if so, to assess the effect of SGLT2 inhibition. Methods: Porcine coronary artery (PCA) rings and cultured endothelial cells (ECs) were exposed to NPs in the presence or absence of the SGLT2 inhibitor, Enavogliflozin (ENA), and the level of SGLTs expression, senescence-associated-beta galactosidase (SA-β-gal) activity, senescence markers, oxidative stress level, and vascular function were evaluated. Results: NPs were internalized in ECs in a time- and concentration-dependent manner. Exposure of PCAECs to NPs significantly up-regulated SGLT2 expression and increased SA-β-gal activity, one of the prominent senescence markers. ENA significantly reduced the NPs-induced increase of SA-β-gal activity in PCA and PCAECs. In addition, ENA prevented the NPs-induced up-regulation of senescence markers, p53, and p21 that promoted the inhibition of ECs proliferation. ENA prevented also the NPs-induced oxidative stress and up-regulation of NOX2 and p22phox in ECs. Exposure of coronary artery rings to NPs blunted endothelium-dependent relaxation and decreased the expression level of endothelial nitric oxide synthase level, and both of these effects were prevented by ENA. Conclusion: The present findings indicate that premature endothelial senescence and dysfunction induced by nanoplastics involve, at least in part, an upregulation of SGLT2, which is associated with increased levels of oxidative stress and the down-regulation of eNOS. They further raise the possibility that SGLT2 may be a potential target for preventing and/or treating environment pollution-associated cardiovascular diseases.