{Reference Type}: Journal Article
{Title}: Compound 3K attenuates isoproterenol-induced cardiac hypertrophy by inhibiting pyruvate kinase M2 (PKM2) pathway.
{Author}: Rihan M;Sharma SS;
{Journal}: Life Sci
{Volume}: 351
{Issue}: 0
{Year}: 2024 Aug 15
{Factor}: 6.78
{DOI}: 10.1016/j.lfs.2024.122837
{Abstract}: <B>OBJECTIVE: </B>Chronic sympathetic stimulation has been identified as a primary factor in the pathogenesis of cardiac hypertrophy (CH). However, there is no appropriate treatment available for the management of CH. Recently, it has been revealed that pyruvate kinase M2 (PKM2) plays a significant role in cardiac remodeling, fibrosis, and hypertrophy. However, the therapeutic potential of selective PKM2 inhibitor has not yet been explored in cardiac hypertrophy. Thus, in the current study, we have studied the cardioprotective potential of Compound 3K, a selective PKM2 inhibitor in isoproterenol-induced CH model.<BR><B>METHODS: </B>To induce cardiac hypertrophy, male Wistar rats were subcutaneously administered isoproterenol (ISO, 5 mg/kg/day) for 14 days. Compound 3K at dosages of 2 and 4 mg/kg orally was administered to ISO-treated rats for 14 days to explore its effects on various parameters like ECG, ventricular functions, hypertrophic markers, histology, inflammation, and protein expression were performed.<BR><B>RESULTS: </B>Fourteen days administration of ISO resulted in the induction of CH, which was evidenced by alterations in ECG, ventricular dysfunctions, increase in hypertrophy markers, and fibrosis. The immunoblotting of hypertrophy heart revealed the significant rise in PKM2 and reduction in PKM1 protein expression. Treatment with Compound 3K led to downregulation of PKM2 and upregulation of PKM1 protein expression. Compound 3K showed cardioprotective effects by improving ECG, cardiac functions, hypertrophy markers, inflammation, and fibrosis. Further, it also reduced cardiac expression of PKM2-associated splicing protein, HIF-1α, and caspase-3.<BR><B>CONCLUSIONS: </B>Our findings suggest that Compound 3K has a potential cardioprotective effect via PKM2 inhibition in isoproterenol-induced CH.