Molecular Mechanisms of Indoor Environmental Pollution tt-DDE-Induced Blood Pressure Elevation and the Protective Role of Human-Specific Gene CHRFAM7A

Cooking oil fumes (COFs), a major source of indoor air pollutants, are responsible for approximately 90% of indoor particulate matter emissions. Trans,trans-2,4-decadienal (tt-DDE), the predominant aldehyde in COFs, exhibits established mutagenic and carcinogenic potential. Although CHRFAM7A remains to be validated as a cardiovascular therapeutic target, accumulating evidence positions it as a novel modulator of the cardiovascular pathophysiology. This study explored the protective mechanisms of CHRFAM7A against the tt-DDE-induced vascular injury. First, inhalation of tt-DDE was observed to elevate blood pressure, an effect attributed to associated endothelial cell damage. Additionally, we found that CHRFAM7A-transgenic mice exhibit significant resistance to tt-DDE-induced systolic hypertension and endothelial dysfunction. Mechanistically, the observed protection was attributed to the STAT3/HO-1 pathway activation. Moreover, in vitro revealed that tt-DDE promotes KLF5-driven inflammatory responses through METTL3-dependent m6A modification, effects that were mitigated by CHRFAM7A overexpression. Notably, inhibition of HO-1 could abolish CHRFAM7A-mediated regulation of METTL3-dependent KLF5 translation. Collectively, these results identify CHRFAM7A as a molecular safeguard against tt-DDE-induced vascular pathology, functioning through coordinated regulation of the STAT3/HO-1/METTL3 signaling. This work thus provides new therapeutic insights for cardiovascular disorders associated with COF exposure.