Cardiovascular disease represents a significant global cause of mortality, with its development and progression closely associated with pathological remodeling of cardiac tissue. Increasing attention has been directed towards environmental pollutants, particularly persistent organic pollutants (POPs), for their potential toxicity to the cardiovascular system. The effects of perfluorodecanoic acid (PFDA) on cardiac health remain inadequately understood. This study investigated the impact of PFDA exposure on cardiomyocyte aging and myocardial fibrosis, alongside the underlying mechanisms involved. Results indicated that PFDA treatment significantly induced cellular senescence and fibrosis-associated phenotypes in both rat H9c2 and mouse HL1 cardiomyocyte cell lines. CCK-8 assays demonstrated a reduction in cardiomyocyte viability following PFDA exposure. Western blot analyses revealed elevated senescence-associated markers, as well as a significant increase in the expression of key fibrotic markers. Additionally, PFDA exposure compromised mitochondrial function in cardiomyocytes, as evidenced by a decline in mitochondrial membrane potential and intracellular ATP levels. ELISA assays confirmed an increase in the secretion of inflammatory cytokines due to PFDA exposure. In vivo experiments utilizing C57BL/6 mice exposed to long-term low-dose PFDA displayed comparable pathological alterations in myocardial tissue. Immunohistochemical analysis revealed a significant increase in collagen fiber deposition within the myocardial interstitium of PFDA-exposed mice, alongside elevated expression levels of COLI and α-SMA compared to the control group. Mechanistically, PFDA exposure resulted in hyperactivation of the MTORC1 signaling axis, characterized by increased phosphorylation of its downstream substrates S6K1 and 4E-BP1 both in vitro and in vivo. Furthermore, activation of AKT was identified as an upstream event that contributes to MTORC1 hyperactivation. In summary, the environmental pollutant PFDA exacerbates cardiomyocyte senescence and activates cardiac fibroblasts through mechanisms that include mitochondrial dysfunction, inflammation promotion, and hyperactivation of the MTORC1 signaling cascade. This research provides novel experimental evidence supporting the role of PFDA pollutants in age-related cardiac diseases.
