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Citations to this article

Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction
Cinzia Perrino, … , Oliver Smithies, Howard A. Rockman
Cinzia Perrino, … , Oliver Smithies, Howard A. Rockman
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1547-1560. https://doi.org/10.1172/JCI25397.
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Research Article Cardiology Article has an altmetric score of 12

Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction

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Abstract

For over a century, there has been intense debate as to the reason why some cardiac stresses are pathological and others are physiological. One long-standing theory is that physiological overloads such as exercise are intermittent, while pathological overloads such as hypertension are chronic. In this study, we hypothesized that the nature of the stress on the heart, rather than its duration, is the key determinant of the maladaptive phenotype. To test this, we applied intermittent pressure overload on the hearts of mice and tested the roles of duration and nature of the stress on the development of cardiac failure. Despite a mild hypertrophic response, preserved systolic function, and a favorable fetal gene expression profile, hearts exposed to intermittent pressure overload displayed pathological features. Importantly, intermittent pressure overload caused diastolic dysfunction, altered β-adrenergic receptor (βAR) function, and vascular rarefaction before the development of cardiac hypertrophy, which were largely normalized by preventing the recruitment of PI3K by βAR kinase 1 to ligand-activated receptors. Thus stress-induced activation of pathogenic signaling pathways, not the duration of stress or the hypertrophic growth per se, is the molecular trigger of cardiac dysfunction.

Authors

Cinzia Perrino, Sathyamangla V. Naga Prasad, Lan Mao, Takahisa Noma, Zhen Yan, Hyung-Suk Kim, Oliver Smithies, Howard A. Rockman

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 2 4 10 8 10 3 5 5 8 5 12 6 6 5 6 5 10 2 6 1 119
Citation information
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Citations to this article in year 2012 (5)

Title and authors Publication Year
Anchored p90 ribosomal S6 kinase 3 is required for cardiac myocyte hypertrophy
J Li, MD Kritzer, JJ Michel, A Le, H Thakur, M Gayanilo, CL Passariello, A Negro, JB Danial, B Oskouei, M Sanders, JM Hare, A Hanauer, K Dodge-Kafka, MS Kapiloff
Circulation research 2012
Can exercise teach us how to treat heart disease?
N Mann, A Rosenzweig
Circulation 2012
Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction
JC Reil, M Hohl, GH Reil, HL Granzier, MT Kratz, A Kazakov, P Fries, A Muller, M Lenski, F Custodis, S Graber, G Frohlig, P Steendijk, HR Neuberger, M Bohm
European Heart Journal 2012
Adult Zebrafish Hearts Efficiently Compensate for Excessive Forced Overload Cardiac Stress with Hyperplastic Cardiomegaly
MJ Jean, P deVerteuil, NH Lopez, JD Tapia, B Schoffstall
BioResearch Open Access 2012
 -Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury
KS Kim, D Abraham, B Williams, JD Violin, L Mao, HA Rockman
American journal of physiology. Heart and circulatory physiology 2012

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Referenced in 11 patents
Referenced in 1 clinical guideline sources
158 readers on Mendeley
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