Cardiac Hypertrophy: The Good, the Bad, and the Ugly

Frey, Norbert; Olson, Eric N.

doi:10.1146/annurev.physiol.65.092101.142243

Cited by 1,309 publications

(1,097 citation statements)

References 224 publications

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“…In the long‐term, however, the initial response may become maladaptive, which is characterized by progressive LV dilation with an inadequate cardiac pumping activity 38, 39. We found in this study that instead of cardiac hypertrophy, decreased LVEF was observed in mice at 4 weeks after TAC, and exogenous HMGB1 overexpression further aggravated the impairment of cardiac function from this perspective.…”

Section: Discussionmentioning

confidence: 54%

Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure

Zhang

Liu

Jiang

et al. 2015

J Cellular Molecular Medi

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Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild‐type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin‐embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC‐induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up‐regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload‐induced cardiac hypertrophy and cardiac dysfunction.

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Section: Discussionmentioning

confidence: 54%

Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure

Zhang

Liu

Jiang

et al. 2015

J Cellular Molecular Medi

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“…3 In an attempt to maintain the necessary blood pressure for organ perfusion, chronic activation of autonomous regulatory mechanisms initiate a vicious cycle of maladaptive structural and functional events that progressively affects all parts of the cardiovascular system. 4,5 Commonly used drugs combating this process tend to attenuate the neurohormonal overactivation, however, by virtue of their mechanism, act enforcedly symptombased, and slow down disease progression only. 6,7 However, steady improvement of our understanding of cellular and molecular processes that contribute to HF pathogenesis prompts continuous development of innovative experimental therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Targeting S100A1 in heart failure

Ritterhoff

Most

2012

Gene Ther

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Heart failure (HF) is the common endpoint of many cardiovascular diseases with a 1-year survival rate of about 50% in advanced stages. Despite increasing survival rates in the past years, current standard therapeutic strategies are far away from being optimal. For this reason, the concept of cardiac gene therapy for the treatment of HF holds great potential to improve disease progression, as it specifically targets key pathologies of diseased cardiomyocytes (CM). The small calcium (Ca 2+ )-binding protein S100A1 presents a promising target for cardiac gene therapy, as it has been identified as a central regulator of cardiac performance and the Ca 2+ -driven network within CM. S100A1 was shown to regulate sarcoplasmic reticulum, sarcomere and mitochondrial function by modulating target protein activity. Furthermore, deranged S100A1 expression has been linked to HF in human ischemic and dilated cardiomyopathies as well as in various HF animal models. Proof-of-concept studies in small and large animal models as wells as in human failing CM could demonstrate feasibility and efficacy of S100A1 genetically targeted therapy. This review summarizes the developmental steps of S100A1 gene therapy for the implementation into first human clinical trials.

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“…Regardless of the initial stimulus, the heart counters these insults with a mechanism known as hypertrophy -a compensatory enlargement of the heart -due to increased biomechanical stress (6).…”

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confidence: 99%