SERCA2a directs the cardioprotective role of nano-emulsion curcumin against PM2.5-induced cardiac injury in rats by prohibiting PERK-eIF2α pathway

Abstract

AimsActivation of endoplasmic reticulum stress (ERS) by particulate matter 2.5 (PM2.5) has recently been linked to an increased risk of heart problems. Although the PERK- eIF2α pathway is known to be involved in ERS, its crucial role in the pathogenesis of PM2.5-induced cardiotoxicity remains unclear. With the expected potentiality of SERCA2a to modulate ERS via inhibiting the PERK-eIF2α axis, this study intended to assess the possible cardioprotective efficacy of nano-emulsion curcumin (NEC), as a SERCA2a activator, against PM2.5-induced heart damage. Main methodsThirty rats were specified into: Vehicle (V); Blank Filter (BF); NEC; PM and NEC + PM. Cardiac biomarkers as PTX3 and cTnI were assayed. The oxidant/antioxidant status was evaluated via detecting Nrf2/HO-1 axis, as well as MDA and TAC. In addition, the protein expressions of PLN, DWORF, SERCA2a, PERK/eIF2α/ATF4/CHOP, and PI3K/AKT/mTOR in the heart were assessed by western blotting. The levels of inflammatory cytokines (TNF-α and IL-1β) and apoptotic markers were also determined. For detecting PM and NEC particles, cardiac tissues were examined using TEM. Key findingsThe results revealed that NEC markedly alleviated the oxidative stress following PM2.5 exposure, up-regulated DWORF, and produced a significant improvement in cardiac functions. Through activating SERCA2a, NEC could hinder ERS, ameliorate PM2.5-associated cardiac inflammation and myocardial apoptosis by suppressing Bax/Bcl-2 ratio and caspase-3 expression, as well as inhibiting autophagy. SignificanceThese findings revealed that NEC may have a SERCA2a-dependent cardioprotective effect against PM2.5-induced cardiac injury via inhibiting the PERK-eIF2 pathway.