Knockdown of LOX-1 ameliorates cardiac hypertrophy in alcoholic cardiomyopathy via inactivating the p38MAPK pathway

Abstract Background One of the characteristics of alcoholic cardiomyopathy (ACM) is cardiac hypertrophy, which was reported to be related to lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), but the mechanism needs to be explored. Here, we explored how LOX-1 facilitated ACM induced cardiac hypertrophy and its molecular mechanisms. Methods H9C2 cells and rats were treated with alcohol to establish ACM models in vitro and in vivo, and before alcohol treatment, H9C2 cells were transfected with sh/oe-LOX-1 and oe-P38MAPK adenovirus vector to knockdown or overexpression LOX-1 and P38MAPK. Hematoxylin-eosin staining (HE) and transmission electron microscopy (TEM) were used to quantify cardiomyocyte area and observe autophagosomes, respectively. RT-qPCR and western blot were used to detect the mRNA and protein expression of LOX-1, P38MAPK, p-P38MAPK, markers of cardiac hypertrophy, autophagy and apoptosis in H9C2 cells and rats, respectively. Furthermore, ACM rats were injected with of sh-LOX-1 to test whether LOX-1 knockdown could alleviate alcohol-induced heart injury by inhibiting the P38MAPK signaling pathway. Results Alcohol induced H9C2 cells hypertrophy, obvious autophagy as well as apoptosis, and increased the expression of LOX-1 and P38MAPK. LOX-1 overexpression enhanced the deleterious effects of alcohol, whereas sh-LOX-1 relatively counteracted. The rescure experiment showed that P38MAPK overexpression partially counteracted the protective effect of LOX-1 knockdown by promoting hypertrophy, autophagy and apoptosis in H9C2 cells. In addition, sh-LOX-1 ameliorated alcohol-induced cardiac injury in rats. Conclusion LOX-1 knockdown could inhibit P38MAPK signaling pathway to exert anti-hypertrophy, anti-autophagy and anti-apoptosis effects in ACM. LOX-1 is expected to be a potential target for the treatment of ACM.