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

Aims: Activation of endoplasmic reticulum stress (ERS) by particulate matter 2.5 (PM) 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 PM-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 PM-induced heart damage.

Main Methods: Thirty 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 Findings: The results revealed that NEC markedly alleviated the oxidative stress following PM exposure, up-regulated DWORF, and produced a significant improvement in cardiac functions. Through activating SERCA2a, NEC could hinder ERS, ameliorate PM-associated cardiac inflammation and myocardial apoptosis by suppressing Bax/Bcl-2 ratio and caspase-3 expression, as well as inhibiting autophagy.

Significance: These findings revealed that NEC may have a SERCA2a-dependent cardioprotective effect against PM-induced cardiac injury via inhibiting the PERK-eIF2 pathway.