Myofibroblast-mediated mechanisms of pathological remodelling of the heart

Research output: Contribution to journalReview article

273 Citations (Scopus)

Abstract

The syncytium of cardiomyocytes in the heart is tethered within a matrix composed principally of type I fibrillar collagen. The matrix has diverse mechanical functions that ensure the optimal contractile efficiency of this muscular pump. In the diseased heart, cardiomyocytes are lost to necrotic cell death, and phenotypically transformed fibroblast-like cells-termed 'myofibroblasts'-are activated to initiate a 'reparative' fibrosis. The structural integrity of the myocardium is preserved by this scar tissue, although at the expense of its remodelled architecture, which has increased tissue stiffness and propensity to arrhythmias. A persisting population of activated myofibroblasts turns this fibrous tissue into a living 'secretome' that generates angiotensin II and its type 1 receptor, and fibrogenic growth factors (such as transforming growth factor-β), all of which collectively act as a signal-transducer-effector signalling pathway to type I collagen synthesis and, therefore, fibrosis. Persistent myofibroblasts, and the resultant fibrous tissue they produce, cause progressive adverse myocardial remodelling, a pathological hallmark of the failing heart irrespective of its etiologic origin. Herein, we review relevant cellular, subcellular, and molecular mechanisms integral to cardiac fibrosis and consequent remodelling of atria and ventricles with a heterogeneity in cardiomyocyte size. Signalling pathways that antagonize collagen fibrillogenesis provide novel strategies for cardioprotection.

Original languageEnglish (US)
Pages (from-to)15-26
Number of pages12
JournalNature Reviews Cardiology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2013

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Myofibroblasts
Cardiac Myocytes
Fibrosis
Atrial Remodeling
Fibrillar Collagens
Angiotensin Type 1 Receptor
Ventricular Remodeling
Transforming Growth Factors
Giant Cells
Collagen Type I
Transducers
Cicatrix
Cardiac Arrhythmias
Heart Diseases
Intercellular Signaling Peptides and Proteins
Myocardium
Cell Death
Collagen
Fibroblasts
Population

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Myofibroblast-mediated mechanisms of pathological remodelling of the heart. / Weber, Karl; Sun, Yao; Bhattacharya, Syamal; Ahokas, Robert A.; Gerling, Ivan.

In: Nature Reviews Cardiology, Vol. 10, No. 1, 01.01.2013, p. 15-26.

Research output: Contribution to journalReview article

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