Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Barandon, Laurent; Couffinhal, Thierry; Ezan, Jérôme; Dufourcq, Pascale; Costet, Pierre; Alzieu, Philippe; Leroux, Lionel; Moreau, Catherine; Dare, Danièle; Duplàa, Cécile

doi:10.1161/01.cir.0000093186.22847.4c

Cited by 198 publications

(221 citation statements)

References 30 publications

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“…Although the molecular mechanisms leading to cardiac rupture after MI remain poorly understood, hypertension, diabetes, cardiac hypertrophy, and use of nonsteroidal antiinflammatory agents are considered as risk factors (29,30). Mice lacking the angiotensin type 2 receptor (31), tissue-type plasminogen activator, urokinase receptor, or metalloelastase are also susceptible to cardiac rupture (32), whereas overexpression of FrzA/sFRP-1, a secreted antagonist of the Wnt/Frizzled pathway (33), and targeted deletion of matrix metalloproteinase-2 (34) and urokinase-type plasminogen activator (32) prevent cardiac rupture in mice after MI. In contrast to MuRF3, these mediators of inflammation and proteolysis are not muscle-specific and may act through different mechanisms than MuRF3 to modulate the response of the heart to acute stress.…”

Section: Discussionmentioning

confidence: 99%

Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

Fielitz¹,

Rooij²,

Spencer³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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RING-finger proteins commonly function as ubiquitin ligases that mediate protein degradation by the ubiquitin-proteasome pathway. Muscle-specific RING-finger (MuRF) proteins are striated muscle-restricted components of the sarcomere that are thought to possess ubiquitin ligase activity. We show that mice lacking MuRF3 display normal cardiac function but are prone to cardiac rupture after acute myocardial infarction. Cardiac rupture is preceded by left ventricular dilation and a severe decrease in cardiac contractility accompanied by myocyte degeneration. Yeast two-hybrid assays revealed four-and-a-half LIM domain (FHL2) and ␥-filamin proteins as MuRF3 interaction partners, and biochemical analyses showed these proteins to be targets for degradation by MuRF3. Accordingly, FHL2 and ␥-filamin accumulated to abnormal levels in the hearts of mice lacking MuRF3. These findings reveal an important role of MuRF3 in maintaining cardiac integrity and function after acute myocardial infarction and suggest that turnover of FHL2 and ␥-filamin contributes to this cardioprotective function of MuRF3.heart failure ͉ cardiac stress response ͉ protein degradation ͉ sarcomere

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Section: Discussionmentioning

confidence: 99%

Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

Fielitz¹,

Rooij²,

Spencer³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…8 Hypertension, cardiac hypertrophy, and infarct expansion are predisposing factors. Previous basic studies suggested that inhibition of plasminogen activators, MMPs, 9 or cardiac overexpression of FrzA can prevent cardiac rupture, 10 whereas deletion of angiotensin AT 2 receptor can aggravate it. 11 However, the upstream regulators of the genes that trigger these responses have not been studied.…”

Section: Discussionmentioning

confidence: 99%

Excessive Tumor Necrosis Factor Activation After Infarction Contributes to Susceptibility of Myocardial Rupture and Left Ventricular Dysfunction

et al. 2004

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Background-We investigated the potential contributions of tumor necrosis factor-␣ (TNF-␣) on the incidence of acute myocardial rupture and subsequent chronic cardiac dysfunction after myocardial infarction (MI) in TNF knockout (TNF Ϫ/Ϫ ) mice compared with C57/BL wild-type (WT) mice. Methods and Results-Animals were randomized to left anterior descending ligation or sham operation and killed on days 3, 7, 14, and 28. We monitored cardiac rupture rate, cardiac function, inflammatory response, collagen degradation, and net collagen formation. We found the following: (1) within 1 week after MI, 53.3% (nϭ120) of WT mice died of cardiac rupture, in contrast to 2.5% (nϭ80) of TNF Ϫ/Ϫ mice; (2) inflammatory cell infiltration and cytokine expression were significantly higher in the infarct zone in WT than TNF Ϫ/Ϫ mice on day 3; (3) matrix metalloproteinase-9 and -2 activity in the infarcted myocardium was significantly higher in WT than in TNF Ϫ/Ϫ mice on day 3; (4) on day 28 after MI compared with sham, there was a significant decrease in LV developed pressure (74%) and ϮdP/dt max (68.3%/65.3%) in WT mice but a less significant decrease in ϮdP/dt max (25.8%/28.8%) in TNF Ϫ/Ϫ mice; (5) cardiac collagen volume fraction was lower in WT than in TNF Ϫ/Ϫ mice on days 3 and 7 but higher on day 28 compared with TNF Ϫ/Ϫ mice; and (6) a reduction in myocyte apoptosis in TNF Ϫ/Ϫ mice occurred on day 28 compared with WT mice. Conclusions-Elevated local TNF-␣ in the infarcted myocardium contributes to acute myocardial rupture and chronic left ventricle dysfunction by inducing exuberant local inflammatory response, matrix and collagen degradation, increased matrix metalloproteinase activity, and apoptosis.

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“…21) In other reports, blocking of Wnt/β-catenin signaling was shown to avert adverse remodeling or improve cardiac function in animal models of myocardial infarction. [22][23][24][25] In spite of such a context-dependency, Wnt/β-catenin signaling is thought to play a pivotal role in the progression of cardiac dysfunction/heart failure. 26) In the canonical Wnt/β-catenin pathway, DKK1 (Dickkopf1) basically inhibits the formation of a ternary complex consisting of LRP5/6, Frizzled, and the Wnt ligand followed by inhibition of the canonical Wnt/β-catenin pathway.…”

Section: Wnt/β-catenin Signaling In the Heartmentioning

confidence: 99%

Heart Failure as an Aging-Related Phenotype

Morita

Komuro

2018

Int. Heart J.

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SummaryThe molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.(Int Heart J 2018; 59: 6-13)

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Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Cited by 198 publications

References 30 publications

Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

Excessive Tumor Necrosis Factor Activation After Infarction Contributes to Susceptibility of Myocardial Rupture and Left Ventricular Dysfunction

Heart Failure as an Aging-Related Phenotype

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