Abstract
Cyanobacterial blooms are considered a serious global environmental problem. Recent studies provided evidence for a positive association between exposure to microcystin-LR (MC-LR) and cardiotoxicity, posing a threat to human cardiovascular health. However, there are few studies on the cardiotoxic effects and mechanisms of long-term low-dose MC-LR exposure. Therefore, this study explored the long-term toxic effects and toxic mechanisms of MC-LR on the heart and provided evidence for the induction of cardiovascular disease by MC-LR. C57BL/6 mice were exposed to 0, 1, 30, 60, 90, and 120 μg/L MC-LR via drinking water for 9 months and subsequently necropsied to examine the hearts for microstructural changes using H&E and Masson staining. The results demonstrated fibrotic changes, and qPCR and Western blots showed a significant up-regulation of the markers of myocardial fibrosis, including TGF-β1, α-SMA, COL1, and MMP9. Through the screening of signaling pathways, it was found the expression of PI3K/AKT/mTOR signaling pathway proteins was up-regulated. These data first suggested MC-LR may induce myocardial fibrosis by activating the PI3K/AKT/mTOR signaling pathway. This study explored the toxicity of microcystins to the heart and preliminarily explored the toxic mechanisms of long-term toxicity for the first time, providing a theoretical reference for preventing cardiovascular diseases caused by MC-LR.