Increased Susceptibility of Cardiac Tissue to PM2.5-Induced Toxicity in Uremic Cardiomyopathic Rats Is Linked to Elevated Levels of Mitochondrial Dysfunction.

Abstract

Patients with chronic kidney disease (CKD) frequently develop uremic cardiomyopathy, characterized by mitochondrial dysfunction as one of its pathologically significant mediators. Given that PM_2.5 specifically targets cardiac mitochondria, exacerbating toxicity, this study addresses the potential alterations in the severity of PM_2.5 toxicity in the context of CKD conditions. Female Wistar rats were exposed to PM_2.5 at a concentration of 250 μg/m³ daily for 3 h for 21 days after which an adenine-induced CKD model was developed. While both PM_2.5 exposure and the induction of CKD in rats lead to cardiomyopathy, the CKD animals exposed to PM_2.5 exhibited a notably severe extent of myocardial hypertrophy and fibrosis. ECG recordings in CKD+ PM_2.5 animals revealed a depressed ST segment and prolonged QRS interval, with both PM_2.5 and CKD animals displaying an elevated ST segment. Subcellular level analysis confirmed a significantly low mitochondrial copy number and a severe decline in mitochondrial bioenergetic function in the CKD+ PM_2.5 group. The prominent decline in PGC1-α further affirmed the severe mitochondrial functional deterioration in CKD+ PM_2.5 animals compared to other experimental groups. Additionally, myocardial calcification was enhanced in CKD+ PM_2.5 animals, heightening the susceptibility of CKD animals to PM_2.5 toxicity. In summary, our findings suggest that the increased vulnerability of CKD myocardium to PM_2.5-induced toxicity may be attributed to severe mitochondrial damage and increased calcification in the myocardium.