ALTERATION IN PLATELET PYRUVATE KINASE ISOENZYME (PKM1/PKM2) EXPRESSION IN CORONARY ARTERY DISEASE AND ISCHEMIC STROKE: A PROSPECTIVE OBSERVATIONAL STUDY OF CLINICAL PROFILE AND PLATELET METABOLIC ADAPTATION

Abstract

Background: Platelets play a key role in arterial thrombosis, causing acute myocardial infarction (AMI) and ischemic stroke. The low-activity dimeric form of pyruvate kinase M2 (PKM2) is involved in mediating a shift in the energy metabolism of activated platelets from oxidative phosphorylation to aerobic glycolysis as compared to PKM2. This balance between the two isoforms has never been investigated in platelets from patients with cardiovascular disease. Methods: This prospective observational study compared the expression of platelet PKM1 and PKM2 by immunoblotting in 12 patients with acute MI or acute ischemic stroke (cases) and 12 controls. Clinical profile, anthropometric parameters, and fasting biochemical variables (HbA1c, lipid profile) were collected, and correlations between the expression of platelet PKM1 and PKM2 were assessed. Results: Mean PKM1 expression was slightly higher in cases (0.94 ± 0.85) compared with controls (0.55 ± 0.53); however, the difference was not significant (p = 0.19). Mean PKM2 expression was slightly lower in cases (1.62 ± 1.11) compared with controls (2.36 ± 1.56). PKM1 correlated positively with HbA1c, and PKM2 correlated negatively with HbA1c and with fasting LDL cholesterol. Conclusions: This reciprocal switch to higher expression of PKM1 and lower expression of PKM2 was seen in the platelets of CAD and stroke patients, and was correlated with glycaemic and lipid risk markers. This imbalance in the expression of PK protein in platelets could be one of the metabolic adaptations that connects the cardiometabolic risk factors to platelet hyperactivity and thrombotic risk in cardiovascular diseases.