Abstract

Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-β1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring.Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-β1-Smad pathway by antibody or the use of triplex-forming oligonucleotides.

Original languageEnglish (US)
Pages (from-to)591-598
Number of pages8
JournalExpert Review of Cardiovascular Therapy
Volume14
Issue number5
DOIs
StatePublished - May 3 2016

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Paracrine Communication
Myofibroblasts
Fibrosis
Collagen
Cicatrix
Autocrine Communication
Fibrillar Collagens
Sclerosis
Actin Cytoskeleton
Oligonucleotides
Angiotensin II
Muscle Cells
Proteolysis
Smooth Muscle Myocytes
Fibroblasts
Apoptosis
Cytokines
Ligands
Antibodies
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Myofibroblast secretome and its auto-/paracrine signaling. / Bomb, Ritin; Heckle, Mark R.; Sun, Yao; Mancarella, Salvatore; Guntaka, Ramareddy; Gerling, Ivan; Weber, Karl.

In: Expert Review of Cardiovascular Therapy, Vol. 14, No. 5, 03.05.2016, p. 591-598.

Research output: Contribution to journalReview article

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