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Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities

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Abstract

As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed “remodeling.” This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin–angiotensin–aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.

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Abbreviations

CAPRICORN:

Carvedilol post infarction survival controlled evaluation trial

MERIT-HF:

Metoprolol CR/XL Randomized Intervention trial in congestive heart failure trial

SAVE:

Survival and ventricular enlargement trial

SOLVD:

Survival in patients with reduced left ventricular ejection fraction and congestive heart failure-treatment trial

TRACE:

Trandolapril Cardiac Evaluation trial

VALIANT:

Valsartan in Acute myocardial infarction trial

RESOLVD:

Randomized Evaluation Strategies of Left Ventricular Dysfunction

RALES:

Randomized Aldactone Evaluation study

EPHESUS:

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study

REPAIR-AMI:

Re-infusion of Enriched Progenitor Cells and Infarct remodeling in Acute Myocardial Infarction trial

PREMIER:

Prevention of Myocardial Infarction Early Remodeling

ESV:

End systolic volume

EDV:

End diastolic volume

EF:

Ejection fraction

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA

    Jason J. Gajarsa

  2. Heart Institute, Good Samaritan Hospital, Keck School of Medicine, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA, 90017, USA

    Robert A. Kloner

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  1. Jason J. Gajarsa
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  2. Robert A. Kloner
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Correspondence to Robert A. Kloner.

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Gajarsa, J.J., Kloner, R.A. Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities. Heart Fail Rev 16, 13–21 (2011). https://doi.org/10.1007/s10741-010-9181-7

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