Global plastic use has increased rapidly, and environmental pollution associated with nanoplastics (NPs) has been a growing concern recently. However, the impact and biological mechanism of NPs on the cardiovascular system are not well characterized. This study aimed to assess the possibility that NPs exposure promotes premature endothelial cell (EC) senescence in porcine coronary artery ECs and, if so, to elucidate the underlying mechanism. Treatment of ECs with NPs promoted the acquisition of senescence markers, senescence-associated β-galactosidase activity, and p53, p21, and p16 protein expression, resulting in the inhibition of proliferation. In addition, NPs impaired endothelium-dependent vasorelaxation associated with decreased endothelial nitric oxide synthase (eNOS) expression. NPs enhanced reactive oxygen species formation in ECs, and increased oxidative stress levels were associated with the induction of NADPH oxidases expression, followed by the subsequent downregulation of Sirt1 expression. The characteristics of EC senescence and dysfunction caused by NPs are prevented by an antioxidant (N-acetylcysteine), an NADPH oxidase inhibitor (apocynin), and a Sirt1 activator (resveratrol). These findings indicate that NPs induced premature EC senescence, at least in part, through the redox-sensitive eNOS/Sirt1 signaling pathway. This study suggested the effects and underlying mechanism of NPs on the cardiovascular system, which may provide pharmacological targets to prevent NPs-associated cardiovascular diseases.

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 p22^phox. 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.

High salt intake causes and aggravates arterial hypertension and vascular dysfunction. We investigated the effect of Salicornia europaea extracts (SE) on vascular function and blood pressure. SE constituents were analyzed using high performance liquid chromatography, and SE’s effect on vascular function was evaluated in isolated porcine coronary arteries. SE’s vascular protective effect was also evaluated in vivo using normotensive and spontaneous hypertensive rats (SHRs). SE mainly contained sodium chloride (55.6%), 5-(hydroxymethyl)furfural, p-coumaric acid, and trans-ferulic acid. High sodium (160 mmol/L) induced vascular dysfunction; however, SE containing the same quantity of sodium did not cause vascular dysfunction. Among the compounds in SE, trans-ferulic acid accounts for the vascular protective effect. Normotensive rats fed a high-salt diet showed significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), which decreased significantly in the SE-treated groups. In SHRs, high edible salt intake significantly increased SBP, DBP, and MAP, but SE intake was associated with a significantly lower MAP. Thus, SE did not induce vascular dysfunction, and trans-ferulic acid might be at least partly responsible for the vasoprotective effect of SE. Taken together, SE could be used as an alternative to purified salt to prevent and ameliorate hypertension.