Gram-negative endotoxin lipopolysaccharide induces cardiac hypertrophy: Detrimental role of Na+–Ca2+ exchanger

摘要: Several molecular pathways involved in the development of cardiac hypertrophy are triggered by perturbation intracellular Ca(2+) homeostasis. Within heart, Na(+)/Ca(2+) exchanger 1 (NCX1) is one main determinant controlling In and heart failure NCX1 expression activity have been reported to be altered. It has shown that chronic bacterial infections (sepsis, endocarditis, myocarditis) can promote hypertrophy. Bacterial stressors, such as Gram-negative endotoxin lipopolysaccharide (LPS), directly or indirectly affect homeostasis induce The present study aimed at evaluating potential link between signal activated LPS-exposed myocytes NCX1. whole rat LPS perfusion induced an early response during which significantly increased. Notably, all these changes were completely prevented NCX inhibitor SN-6. We further dissect role LPS-induced hypertrophic vitro model based on two H9c2 cardiomyoblast clones, namely H9c2-WT (lacking endogenous expression) H9c2-NCX1 (stably transfected with a functional NCX1). more susceptible than develop phenotype, they displayed significant increase function after treatment. SN-6 counteracted both alterations cells, but it had no effects H9c2-WT. Collectively, our results suggest plays critical promoting myocardial LPS.