NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity

被引:18
作者
Hafstad, Anne D. [1 ]
Hansen, Synne S. [1 ]
Lund, Jim [1 ]
Santos, Celio X. C. [2 ]
Boardman, Neoma T. [1 ]
Shah, Ajay M. [2 ]
Aasum, Ellen [1 ]
机构
[1] UIT Arctic Univ Norway, Cardiovasc Res Grp, Dept Med Biol, Fac Hlth Sci, N-9019 Tromso, Norway
[2] Kings Coll London, British Heart Fdn Ctr Excellence, Sch Cardiovasc Med & Sci, London SE5 9NU, England
关键词
obesity; ROS; NADPH-oxidase; myocardial oxygen consumption; metabolism; cardiac efficiency; INSULIN-RESISTANCE; CARDIAC EFFICIENCY; CONTRACTILE FUNCTION; OXIDATIVE STRESS; PERFUSED HEARTS; NOX2; METABOLISM; ACTIVATION; MICE; CARDIOPROTECTION;
D O I
10.3390/antiox9020171
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Obesity and diabetes are independent risk factors for cardiovascular diseases, and they are associated with the development of a specific cardiomyopathy with elevated myocardial oxygen consumption (MVO2) and impaired cardiac efficiency. Although the pathophysiology of this cardiomyopathy is multifactorial and complex, reactive oxygen species (ROS) may play an important role. One of the major ROS-generating enzymes in the cardiomyocytes is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), and many potential systemic activators of NOX2 are elevated in obesity and diabetes. We hypothesized that NOX2 activity would influence cardiac energetics and/or the progression of ventricular dysfunction following obesity. Myocardial ROS content and mechanoenergetics were measured in the hearts from diet-induced-obese wild type (DIOWT) and global NOK2 knock-out mice (DIOKO) and in diet-induced obese C57BL/6J mice given normal water (DIO) or water supplemented with the NOX2-inhibitor apocynin (DIOAPO). Mitochondrial function and ROS production were also assessed in DIO and DIOAPO mice. This study demonstrated that ablation and pharmacological inhibition of NOX2 both improved mechanical efficiency and reduced MVO2 for non-mechanical cardiac work. Mitochondrial ROS production was also reduced following NOX2 inhibition, while cardiac mitochondrial function was not markedly altered by apocynin-treatment. Therefore, these results indicate a link between obesity-induced myocardial oxygen wasting, NOX2 activation, and mitochondrial ROS.
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页数:17
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