SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction

Abstract

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.

An Emerging Role of Micro- and Nanoplastics in Vascular Diseases

“…NPs significantly upregulated SGLT2 and senescence-associated-β-galactosidase (SA-β-gal) activity, whereas suppression of SGLT2 significantly diminished SA-β-gal activity in porcine coronary artery endothelial cells (PCAEC). This study highlights the association of premature endothelial senescence by NPs with SGLT2 and provides a potential therapeutic target to prevent environmental pollutant-elicited cardiovascular diseases mediated by endothelial senescence and dysfunction [75]. Basini et al revealed the potential effects of NPs on endothelial aortic cells (AOCs) by evaluating the ability of NPs to specifically interact with endothelial cells using fluorescence microscopy.…”

Nanoplastics as emerging cardiovascular hazards: a narrative review of current evidence

“…Studying NPs presents a multifaceted challenge that demands meticulous attention and innovative solutions [43,44,48]. With plastic production surging to unprecedented levels, concerns regarding environmental contamination and potential health risks have escalated proportionally [43,48]. A primary obstacle in studying NPs lies in their interactions with biological systems and their diverse routes of exposure [43,48].…”

“…With plastic production surging to unprecedented levels, concerns regarding environmental contamination and potential health risks have escalated proportionally [43,48]. A primary obstacle in studying NPs lies in their interactions with biological systems and their diverse routes of exposure [43,48]. While efforts have focused on identifying their presence in organs like the intestine and placenta, direct in vivo evidence remains limited [43,48].…”

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

“…Secondly, exposure to these pollutants can induce increased DNA damage and cellular senescence [159][160][161][162][163]. DNA damage can occur due to direct interaction with the genetic material or through the generation of ROS.…”