Cardiovascular Pharmacology: Open Access

S-nitrosylation of transglutaminase 2 impairs fatty acid-stimulated contraction in hypertensive cardiomyocytes

Joint Event on Heart Failure, Pediatric Cardiology & Nursing Education

February 18-19, 2019 | Amsterdam, Netherlands

Yin Hua Zhang

Seoul National University, Korea

Scientific Tracks Abstracts: Cardiovasc Pharm Open Access

Abstract:

Transglutaminase 2 (TG2) is a calcium-dependent enzyme and in the cardiovascular system, TG2 has been reported to be involved in the development of cardiac hypertrophy, vessel remodeling, and age-related vascular stiffness. Interestingly, TG2 is implicated in the regulation of muscle metabolism via modification of respiratory complexes and the ADP/ATP transporter in the mitochondria of myocardium. However, the role of TG2 in the heart during conditions of pressure overload in relation to fatty acid (FA) oxidation has not been investigated. Hence, we investigated the involvement of TG2 in cardiomyocytes contraction under FA supplementation. Using TG2 inhibitor and TG2- deficient mice, we demonstrated that FA-supplementation activated TG2 and increased ATP level and contractility of cardiac myocyte from normal heart. By contrast, in cardiac myocytes from angiotensin-II treated rats and mice, the effects of FA-supplementation on TG2 activity, ATP level and myocyte contraction were abolished. Furthermore, TG2 was inhibited by S-nitrosylation and its level increased in hypertensive myocytes. Treatment with inhibitor for neuronal nitric oxide synthase (nNOS) restored FA-induced increase of TG2 activity and myocyte contraction. Moreover, intracellular Ca2+ levels were increased by FA-supplementation in both normal and hypertensive myocytes, showing that S-nitrosylation of TG2 but not alteration of intracellular Ca2+ levels are responsible for contractile dysfunction. These results indicate that TG2 plays a critical role in the regulation of myocyte contractility by promoting FA metabolism and provide a novel target for preventing contractile dysfunction in heart with high work-load.

Biography :

Yin Hua Zhang is a Cardiovascular Physiologist evaluating cardiac metabolism in health and diseased hearts. She has been working on nitric oxide and redox-regulation of myocardial contractility and cellular mechanisms. She is now focusing on obesity and hypertension and cardiovascular remodeling.

E-mail: yinzhang87@googlemail.com