PCSK9 inhibitor improved cardiac function after acute myocardial infarction in rats

This study investigated the effects and possible mechanisms of Protein expression of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac function in rats with acute myocardial infarction (AMI).

The AMI model was established by ligating the left anterior descending coronary artery in rats. The mRNA expression of PCSK9 in myocardial tissues was detected by real-time fluorescent quantitative PCR (RT-qPCR). Echocardiography was used to examine the cardiac function indexes. Hematoxylin-eosin (HE) and Masson stainings were used to detect myocardial pathologic injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect myocardial infarction area. Serum levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), interleukin-1β (IL-1β), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. CD31 and vascular endothelial growth factor (VEGF) positive expression was detected by immunohistochemistry. Protein expression levels of PCSK9, Bax, Bcl-2, cleaved-caspase3, receptor interacting protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like (MLKL), and p-MLKL were detected in myocardial tissues by western blot.

The mRNA level and protein expression of PCSK9 were significantly increased in AMI rats. PCSK9 inhibitor evolocumab reduced the levels of LDL-C and TC in serum, thereby improving dyslipidemia. And, evolocumab up-regulated the levels of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and down-regulated the levels of left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), and left ventricular end diastolic volume (LVEDV), which in turn improved cardiac function. In addition, evolocumab attenuated myocardial pathological injury, reduced myocardial infarction area, lowered the levels of LDH, CK-MB, cTnT, IL-1β, IL-17, and TNF-α, and inhibited apoptosis rate, down-regulated Bax, cleaved-caspase3, RIPK1, RIPK3, MLKL, p-MLKL expression, and up-regulated Bcl-2 protein expression, CD31 and VEGF positive expression.

The PCSK 9 inhibitor evolocumab improved cardiac function in AMI rats, and the mechanism may be related to the RIPK1/RIPK3/MLKL pathway.