Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice

Diwan, Abhinav; Krenz, Maike; Syed, Faisal M.; Wansapura, Janaka; Xiaoping Ren; Koesters, Andrew G.; Hairong Li; Kirshenbaum, Lorrie A.; Hahn, Harvey S.; Robbins, Jeffrey; Jones, W. Keith; Dorn II, Gerald W.; Ren, Xiaoping; Li, Hairong; Dorn, Gerald W
October 2007
Journal of Clinical Investigation;Oct2007, Vol. 117 Issue 10, p2825
Academic Journal
journal article
Following myocardial infarction, nonischemic myocyte death results in infarct expansion, myocardial loss, and ventricular dysfunction. Here, we demonstrate that a specific proapoptotic gene, Bnip3, minimizes ventricular remodeling in the mouse, despite having no effect on early or late infarct size. We evaluated the effects of ablating Bnip3 on cardiomyocyte death, infarct size, and ventricular remodeling after surgical ischemia/reperfusion (IR) injury in mice. Immediately following IR, no significant differences were observed between Bnip3(-/-) and WT mice. However, at 2 days after IR, apoptosis was diminished in Bnip3(-/-) periinfarct and remote myocardium, and at 3 weeks after IR, Bnip3(-/-) mice exhibited preserved LV systolic performance, diminished LV dilation, and decreased ventricular sphericalization. These results suggest myocardial salvage by inhibition of apoptosis. Forced cardiac expression of Bnip3 increased cardiomyocyte apoptosis in unstressed mice, causing progressive LV dilation and diminished systolic function. Conditional Bnip3 overexpression prior to coronary ligation increased apoptosis and infarct size. These studies identify postischemic apoptosis by myocardial Bnip3 as a major determinant of ventricular remodeling in the infarcted heart, suggesting that Bnip3 may be an attractive therapeutic target.


Related Articles

  • Nipping at cardiac remodeling. Whelan, Russell S.; Mani, Kartik; Kitsis, Richard N. // Journal of Clinical Investigation;Oct2007, Vol. 117 Issue 10, p2751 

    Much of the mortality following myocardial infarction results from remodeling of the heart after the acute ischemic event. Cardiomyocyte apoptosis has been thought to play a key role in this remodeling process. In this issue of the JCI, Diwan and colleagues present evidence that Bnip3, a...

  • Syndecan-4 signalling inhibits apoptosis and controls NFAT activity during myocardial damage and remodelling. Echtermeyer, Frank; Harendza, Thomas; Hubrich, Svenja; Lorenz, Anika; Herzog, Christine; Mueller, Martin; Schmitz, Martina; Grund, Andrea; Larmann, Jan; Stypmann, Jörg; Schieffer, Bernhard; Lichtinghagen, Ralf; Hilfiker-Kleiner, Denise; Wollert, Kai C.; Heineke, Jörg; Theilmeier, Gregor // Cardiovascular Research;Oct2011, Vol. 92 Issue 1, p123 

    Aims Myocardial infarction (MI) results in acute impairment of left ventricular (LV) function through the initial development of cardiomyocyte death and subsequent progression of LV remodelling. The expression of syndecan-4 (Sdc4), a transmembrane proteoglycan, is up-regulated after MI, but its...

  • TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. Haudek, Sandra B.; Taffet, George E.; Schneider, Michael D.; Mann, Douglas L. // Journal of Clinical Investigation;Sep2007, Vol. 117 Issue 9, p2692 

    Transgenic mice with cardiac-restricted overexpression of secretable TNF (MHCsTNF) develop progressive LV wall thinning and dilation accompanied by an increase in cardiomyocyte apoptosis and a progressive loss of cytoprotective Bcl-2. To test whether cardiac-restricted overexpression of Bcl-2...

  • Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation. Li, Xiangrao; Zhou, Jian; Huang, Kai // Cellular Physiology & Biochemistry (Karger AG);Oct2017, Vol. 42 Issue 3, p1153 

    Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes...

  • IL-33 Attenuates Anoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Inhibition of PKCβ/JNK Pathway. Rui, Tao; Tang, Qizhu // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    Background: Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family. The objectives of present study are to assess whether IL-33 can protect cardiomyocytes from anoxia/reoxygenation (A/R)-induced injury and the mechanism involved in the protection. Methods: Cardiomyocytes...

  • ERK-MAPK Signaling Opposes Rho-Kinase to Reduce Cardiomyocyte Apoptosis in Heart Ischemic Preconditioning. Juan-Zhang; Hong-Jun Bian; Xiao-Xing Li; Xiao-Bo Liu; Jun-Ping Sun; Na-Li; Yun-Zhang; Xiao-Ping Ji // Molecular Medicine;Jul/Aug2010, Vol. 16 Issue 7/8, p307 

    We and others have reported that Rho-kinase plays an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. Studies have also demonstrated that the activation of Rho-kinase is reversed in ischemic preconditioning (IPC). However, the mechanisms by which Rho-kinase is...

  • NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice. Li, Xiang; Li, Fengli; Chu, Yongli; Wang, Xiaojie; Zhang, Hongyu; Hu, Yanyan; Zhang, Yan; Wang, Ziying; Wei, Xinbing; Jian, Wencheng; Zhang, Xiumei; Yi, Fan // Cellular Physiology & Biochemistry (Karger AG);Dec2013, Vol. 32 Issue 6, p1857 

    Background/Aims: Although the pathogenesis of myocardial infarction (MI) is multifactorial, activation of innate immune system to induce inflammation has emerged as a key pathophysiological process in MI. NOD2, one member of the NOD-like receptor (NLR) family, plays an important role in the...

  • miR-24 Regulates Intrinsic Apoptosis Pathway in Mouse Cardiomyocytes. Wang, Li; Qian, Li // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Numerous cardiac diseases, including myocardial infarction (MI) and chronic heart failure, have been associated with cardiomyocyte apoptosis. Promoting cell survival by inhibiting apoptosis is one of the effective strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. miR-24...

  • Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis. Meischl, C.; Krijnen, P. A. J.; Sipkens, J. A.; Cillessen, S. A. G. M.; Gámez Muñoz, I.; Okroj, M.; Ramska, M.; Muller, A.; Visser, C. A.; Musters, R. J. P.; Simonides, W. S.; Hack, C. E.; Roos, D.; Niessen, H. W. M. // Apoptosis;Jun2006, Vol. 11 Issue 6, p913 

    In previous work we have demonstrated increased expression of NOX2 in cardiomyocytes of infarcted human hearts. In the present manuscript we investigated the functional role of NOX2 in ischemically challenged H9c2 cells, a rat cardiomyoblast cell line, and adult rat cardiomyocytes. Expression of...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics