![]() ![]() Moreover, the G allele appears to affect the expression levels of the gene, reducing the mRNA amounts. Regarding polymorphisms in PLA2G4A, intronic variant rs12746200 has been identified as a protective variant against CVD development in particular, it is the derived G allele that reduces the risk of cardiovascular diseases because people carrying GG or AG genotypes show a lower likelihood of major adverse cardiac events (MACE) than AA genotype carriers. ![]() ![]() On the other hand, another study on knockout mice has displayed that inhibition of cPLA2α decreases the myocardial infarct size and preserves left ventricle function, attenuating myocardial ischemia and reperfusion injury owing to a lower cleavage of arachidonic acid and the subsequent synthesis of pro-inflammatory and cardiotoxic eicosanoids. On one hand, an in vivo study on cPLA2α −/− knockout mice has shown that the absence of this enzyme increases infarction size and reperfusion injury after myocardial ischemia. However, there are conflicting and opposing data on the association of cPLA2α with myocardial ischemia. This enzyme is activated by different molecules, such as pro-inflammatory interleukin-1α (IL-1α) and tumor necrosis factor α (TNF-α), both of which are produced in response to myocardial ischemia, and contributes to myocardial infarction and reperfusion injury. Among PLA2 enzymes, the cytosolic PLA2α, encoded by the PLA2G4A gene, is well characterized and plays a central role in the release of AA, showing a strong substrate specificity for this PUFA. ![]()
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