Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function

Mark R. Heckle, David M. Flatt, Yao Sun, Salvatore Mancarella, Tony Marion, Ivan Gerling, Karl Weber

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cardiomyocytes must be responsive to demands placed on the heart’s contractile work as a muscular pump. In turn, myocyte size is largely dependent on the workload they perform. Both hypertrophied and atrophic myocytes are found in the normal and diseased ventricle. Individual myocytes become atrophic when encumbered by fibrillar collagen, such as occurs at sites of fibrosis. The mechanisms include: (a) being immobilized and subject to disuse with ensuing protein degradation mediated by redox-sensitive, proteolytic ligases of the ubiquitin–proteasome system and (b) dedifferentiated re-expressing fetal genes induced by low intracellular triiodothyronine (T3) via thyroid hormone receptor β1. This myocyte-selective, low T3 state is a consequence of heterocellular signaling emanating from juxtaposed scar tissue myofibroblasts and their secretome with its de novo generation of angiotensin II. In a paracrine manner, angiotensin II promotes myocyte Ca2+ entry and subsequent Ca2+ overload with ensuing oxidative stress that overwhelms antioxidant defenses to activate deiodinase-3 and its enzymatic degradation of T3. In the failing heart, atrophic myocytes represent an endogenous population of viable myocytes which could be rescued to augment contractile mass, reduce systolic wall stress (afterload) and recover ventricular function. Experimental studies have shown the potential for the rescue and recovery of atrophic myocytes in rebuilding the myocardium—a method complementary to today’s quest in regenerating myocardium using progenitor cells.

Original languageEnglish (US)
Pages (from-to)191-198
Number of pages8
JournalHeart Failure Reviews
Volume21
Issue number2
DOIs
StatePublished - Mar 1 2016

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Ventricular Function
Recovery of Function
Cardiac Myocytes
Muscle Cells
Triiodothyronine
Angiotensin II
Fibrillar Collagens
Thyroid Hormone Receptors
Iodide Peroxidase
Myofibroblasts
Ligases
Workload
Proteolysis
Oxidation-Reduction
Cicatrix
Myocardium
Oxidative Stress
Fibrosis
Stem Cells
Antioxidants

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function. / Heckle, Mark R.; Flatt, David M.; Sun, Yao; Mancarella, Salvatore; Marion, Tony; Gerling, Ivan; Weber, Karl.

In: Heart Failure Reviews, Vol. 21, No. 2, 01.03.2016, p. 191-198.

Research output: Contribution to journalArticle

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