Carbonic Anhydrase Activation Is Associated With Worsened Pathological Remodeling in Human Ischemic Diabetic Cardiomyopathy

被引:82
作者
Torella, Daniele [1 ,2 ]
Ellison, Georgina M. [1 ,3 ,4 ]
Torella, Michele [7 ]
Vicinanza, Carla [1 ,2 ]
Aquila, Iolanda [1 ]
Iaconetti, Claudio [1 ]
Scalise, Mariangela [1 ]
Marino, Fabiola [1 ]
Henning, Beverley J. [2 ]
Lewis, Fiona C. [3 ,4 ]
Gareri, Clarice [1 ]
Lascar, Nadia [5 ,6 ]
Cuda, Giovanni [8 ]
Salvatore, Teresa [5 ,6 ]
Nappi, Gianantonio [7 ]
Indolfi, Ciro [1 ]
Torella, Roberto [5 ,6 ]
Cozzolino, Domenico [5 ,6 ]
Sasso, Ferdinando Carlo [5 ,6 ]
机构
[1] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, I-88100 Catanzaro, Italy
[2] Liverpool John Moores Univ, Fac Sci, Stem Cell & Regenerat Biol Unit BioStem, Liverpool L3 5UX, Merseyside, England
[3] Kings Coll London, Sch Biomed Sci, Ctr Human & Aerosp Physiol Sci, London, England
[4] Kings Coll London, Sch Biomed Sci, Ctr Stem Cells & Regenerat Med, London, England
[5] Univ Naples 2, Ctr Cardiovasc Excellence, Naples, Italy
[6] Univ Naples 2, Dept Internal & Expt Med Lanzara Magrassi, Unit Internal Med, Naples, Italy
[7] Univ Naples 2, Dept Cardiothorac & Resp Sci, Naples, Italy
[8] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Lab Prote & Mass Spectrometry, Catanzaro, Italy
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2014年 / 3卷 / 02期
关键词
apoptosis; carbonic anhydrase; diabetes mellitus; hypertrophy; microRNA; SODIUM-HYDROGEN EXCHANGER; CARDIAC STEM-CELL; HEART-FAILURE; MYOCARDIAL-INFARCTION; OXIDATIVE STRESS; MICRORNAS; HYPERTROPHY; INHIBITION; EXPRESSION; PERMEABILITY;
D O I
10.1161/JAHA.113.000434
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Diabetes mellitus (DM) has multifactorial detrimental effects on myocardial tissue. Recently, carbonic anhydrases (CAs) have been shown to play a major role in diabetic microangiopathy but their role in the diabetic cardiomyopathy is still unknown. Methods and Results-We obtained left ventricular samples from patients with DM type 2 (DM-T2) and nondiabetic (NDM) patients with postinfarct heart failure who were undergoing surgical coronary revascularization. Myocardial levels of CA-I and CA-II were 6- and 11-fold higher, respectively, in DM-T2 versus NDM patients. Elevated CA-I expression was mainly localized in the cardiac interstitium and endothelial cells. CA-I induced by high glucose levels hampers endothelial cell permeability and determines endothelial cell apoptosis in vitro. Accordingly, capillary density was significantly lower in the DM-T2 myocardial samples (mean +/- SE = 2152 +/- 146 versus 4545 +/- 211/mm(2)). On the other hand, CA-II was mainly upregulated in cardiomyocytes. The latter was associated with sodium-hydrogen exchanger-1 hyperphosphorylation, exaggerated myocyte hypertrophy (cross-sectional area 565 +/- 34 versus 412 +/- 27 mu m(2)), and apoptotic death (830 +/- 54 versus 470 +/- 34 per 10(6) myocytes) in DM-T2 versus NDM patients. CA-II is activated by high glucose levels and directly induces cardiomyocyte hypertrophy and death in vitro, which are prevented by sodium-hydrogen exchanger-1 inhibition. CA-II was shown to be a direct target for repression by microRNA-23b, which was downregulated in myocardial samples from DM-T2 patients. MicroRNA-23b is regulated by p38 mitogen-activated protein kinase, and it modulates high-glucose CA-II-dependent effects on cardiomyocyte survival in vitro. Conclusions-Myocardial CA activation is significantly elevated in human diabetic ischemic cardiomyopathy. These data may open new avenues for targeted treatment of diabetic heart failure.
引用
收藏
页数:16
相关论文
共 48 条
  • [1] Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy
    Alvarez, Bernardo V.
    Johnson, Danielle E.
    Sowah, Daniel
    Soliman, Daniel
    Light, Peter E.
    Xia, Ying
    Karmazyn, Morris
    Casey, Joseph R.
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2007, 579 (01): : 127 - 145
  • [2] Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
    Alvarez, Bernardo V.
    Quon, Anita L.
    Mullen, John
    Casey, Joseph R.
    [J]. BMC CARDIOVASCULAR DISORDERS, 2013, 13
  • [3] Coronary heart disease in patients with diabetes - Part I: Recent advances in prevention and noninvasive management
    Berry, Colin
    Tardif, Jean-Claude
    Bourassa, Martial G.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (06) : 631 - 642
  • [4] Diabetic cardiomyopathy revisited
    Boudina, Sihem
    Abel, E. Dale
    [J]. CIRCULATION, 2007, 115 (25) : 3213 - 3223
  • [5] Contribution of Impaired Myocardial Insulin Signaling to Mitochondrial Dysfunction and Oxidative Stress in the Heart
    Boudina, Sihem
    Bugger, Heiko
    Sena, Sandra
    O'Neill, Brian T.
    Zaha, Vlad G.
    Ilkun, Olesya
    Wright, Jordan J.
    Mazumder, Pradip K.
    Palfreyman, Eric
    Tidwell, Timothy J.
    Theobald, Heather
    Khalimonchuk, Oleh
    Wayment, Benjamin
    Sheng, Xiaoming
    Rodnick, Kenneth J.
    Centini, Ryan
    Chen, Dong
    Litwin, Sheldon E.
    Weimer, Bart E.
    Abel, E. Dale
    [J]. CIRCULATION, 2009, 119 (09) : 1272 - U111
  • [6] Revisiting the principles of microRNA target recognition and mode of action
    Brodersen, Peter
    Voinnet, Olivier
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (02) : 141 - 148
  • [7] Carbonic anhydrase II promotes cardiomyocyte hypertrophy
    Brown, Brittany F.
    Quon, Anita
    Dyck, Jason R. B.
    Casey, Joseph R.
    [J]. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2012, 90 (12) : 1599 - 1610
  • [8] MicroRNAs in Cardiovascular Biology and Heart Disease
    Catalucci, Daniele
    Gallo, Paolo
    Condorelli, Gianluigi
    [J]. CIRCULATION-CARDIOVASCULAR GENETICS, 2009, 2 (04) : 402 - 408
  • [9] Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy
    Cingolani, Horacio E.
    Ennis, Irene L.
    [J]. CIRCULATION, 2007, 115 (09) : 1090 - 1100
  • [10] Angiotensin II-mediated phenotypic cardiomyocyte remodeling leads to age-dependent cardiac dysfunction and failure
    Domenighetti, AA
    Wang, Q
    Egger, M
    Richards, SM
    Pedrazzini, T
    Delbridge, LMD
    [J]. HYPERTENSION, 2005, 46 (02) : 426 - 432