Commentary - Journal of Translational Research (2022) Volume 6, Issue 5
An acute myocardial infarction, the heart function of rats was restored due to the therapeutic effects of adipose derived fresh stromal vascular fraction-containing stem cells versus cultured adipose derived mesenchymal stem cells.
Ser/Thr kinase LRRK2 has several functional domains. LRRK2 mutations have been linked to hereditary Parkinson's disease, according to studies. Uncertainty surrounds its function in cardiovascular disease, particularly myocardial infarction. This study's objective was to investigate LRRK2's functional role in myocardial infarction. To create a myocardial infarction model, coronary arteries (left anterior descending) were cut in wild-type and LRRK2-knockout mice. Cardiomyocytes from newborn rats were exposed to hypoxia to cause hypoxic injury in culture. In mouse hearts and hypoxic cardiomyocytes, we observed elevated LRRK2 expression levels in the infarct periphery. 14 days after infarction, LRRK2-deficient mice showed lower death rates and smaller infarction areas than wild-type controls. Reduced inflammation and left ventricular fibrosis were seen in LRRK2-deficient. In the in vitro study, LRRK2 silencing decreased the activity of cleaved caspase-3, decreased cardiomyocyte apoptosis, and decreased inflammation brought on by hypoxia. However, LRRK2 overexpression boosted cleaved caspase-3 activity, raised the number of cardiomyocytes that were apoptotic, and dramatically increased inflammation brought on by hypoxia. We discovered that hypoxia increased HIF expression, which improved LRRK2 expression, when we looked at the underlying mechanisms. Through P53, LRRK2 increased the expression of HMGB1. The detrimental effects of LRRK2 overexpression following hypoxia were inhibited in cardiomyocytes when HMGB1 was blocked by an anti-HMGB1 antibody. In conclusion, LRRK2 deficiency protects the heart from damage caused by myocardial infarction. The P53-HMGB1 is involved in the mechanism causing this effect.Author(s): Roberta Cesaro