INTERLEUKIN-6 INDUCED ENHANCEMENT OF BRAIN NATRIURETIC PEPTIDE THROUGH JAK2/STAT3 ACTIVATION IN CARDIOMYOCYTES: IMPLICATIONS FOR ATHLETE HEART HEALTH

Abstract

Background: Acute coronary syndrome (ACS) in athletes is often linked with elevated levels of brain natriuretic peptide (BNP), a critical biomarker for cardiovascular distress. Understanding the molecular basis of this elevation can aid in the management of athlete heart health. Aim: This study explores the influence of interleukin-6 (IL-6) on BNP expression in cardiomyocytes, particularly under stress conditions that simulate athletic performance. Methods: Neonatal rat cardiomyocytes were subjected to a hypoxia simulation to mimic exercise-induced stress. The expression of IL-6 and BNP was quantified using quantitative real-time polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assays (ELISA). The activation states of the JAK2 and STAT3 proteins, key components of the signaling pathway influenced by IL-6, were analyzed via Western blotting. Results: Hypoxic conditions led to a significant increase in both IL-6 and BNP levels (P<0.05). Additionally, exogenous IL-6 further enhanced BNP expression, correlating with increased phosphorylation of JAK2 and STAT3 (P<0.05). The IL-6 driven augmentation of BNP was partially inhibited by AG490, a JAK2 inhibitor, indicating the JAK2/STAT3 axis's role in this regulatory pathway. Co-treatment with AG490 and a TGF-β neutralizing antibody modestly reduced the effects of IL-6, underscoring the complexity of cytokine interactions in cardiomyocytes. Conclusion: IL-6 significantly influences BNP expression in cardiomyocytes through the JAK2/STAT3 signaling pathway. This pathway may be a potential target for interventions designed to manage cardiovascular health in athletes, particularly those under high physical stress. The findings emphasize the need for comprehensive cardiovascular monitoring and potential therapeutic targeting in athletes to prevent adverse outcomes related to elevated BNP levels during intense physical activity.