Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

被引：216

作者：

Luo, Min ^{[1
]}

Guan, Xiaoqun ^{[1
]}

Luczak, Elizabeth D. ^{[1
]}

Lang, Di ^{[2
]}

Kutschke, William ^{[1
]}

Gao, Zhan ^{[1
]}

Yang, Jinying ^{[1
]}

Glynn, Patric ^{[3
]}

Sossalla, Samuel ^{[4
]}

Swaminathan, Paari D. ^{[1
]}

Weiss, Robert M. ^{[1
]}

Yang, Baoli ^{[5
,6
]}

Rokita, Adam G. ^{[1
,4
]}

Maier, Lars S. ^{[4
]}

Efimov, Igor R. ^{[2
]}

Hund, Thomas J. ^{[3
]}

Anderson, Mark A. ^{[1
,7
]}

机构：

[1] Univ Iowa, Dept Internal Med, Cardiovasc Res Ctr, Carver Coll Med,Div Cardiovasc Med, Iowa City, IA 52242 USA

[2] Washington Univ, Dept Biomed Engn, St Louis, MO USA

[3] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA

[4] Univ Gottingen, Dept Cardiol, D-37073 Gottingen, Germany

[5] Univ Iowa, Gene Targeting Core Facil, Iowa City, IA USA

[6] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA

[7] Univ Iowa, Dept Mol Physiol & Biophys, Carver Coll Med, Iowa City, IA USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 03期

关键词：

CALMODULIN KINASE-II; HEART-RATE-VARIABILITY; OXIDATIVE STRESS; SUDDEN-DEATH; MITOCHONDRIAL SUPEROXIDE; CARDIAC-HYPERTROPHY; GLUCOSE; MELLITUS; CALCIUM; HYPERGLYCEMIA;

D O I：

10.1172/JCI65268

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKII delta (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction.

引用

页码：1262 / 1274

页数：13

共 72 条

[1] EXERCISE TESTING WITH MYOCARDIAL SCINTIGRAPHY IN ASYMPTOMATIC DIABETIC MALES [J].

ABENAVOLI, T ;

RUBLER, S ;

FISHER, VJ ;

AXELROD, HI ;

ZUCKERMAN, KP .

CIRCULATION, 1981, 63 (01) :54-64

[2]

[Anonymous], LANCET

[3]

[Anonymous], J CLIN INVEST

[4]

[Anonymous], LANCET, V352, P837, DOI DOI 10.1016/S0140-6736(98)07019-6

[5]

[Anonymous], DIABETES CARE

[6] Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction [J].

Aronson, D ;

Rayfield, EJ ;

Chesebro, JH .

ANNALS OF INTERNAL MEDICINE, 1997, 126 (04) :296-306

[7] The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload [J].

Backs, Johannes ;

Backs, Thea ;

Neef, Stefan ;

Kreusser, Michael M. ;

Lehmann, Lorenz H. ;

Patrick, David M. ;

Grueter, Chad E. ;

Qi, Xiaoxia ;

Richardson, James A. ;

Hill, Joseph A. ;

Katus, Hugo A. ;

Bassel-Duby, Rhonda ;

Maier, Lars S. ;

Olson, Eric N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (07) :2342-2347

[8] Diabetic cardiomyopathy revisited [J].

Boudina, Sihem ;

Abel, E. Dale .

CIRCULATION, 2007, 115 (25) :3213-3223

[9] The pathobiology of diabetic complications - A unifying mechanism [J].

Brownlee, M .

DIABETES, 2005, 54 (06) :1615-1625

[10] Mechanistic Links Between Na+ Channel (SCN5A) Mutations and Impaired Cardiac Pacemaking in Sick Sinus Syndrome [J].

Butters, Timothy D. ;

Aslanidi, Oleg V. ;

Inada, Shin ;

Boyett, Mark R. ;

Hancox, Jules C. ;

Lei, Ming ;

Zhang, Henggui .

CIRCULATION RESEARCH, 2010, 107 (01) :126-U276

← 1 2 3 4 5 6 7 8 →