Angiotensin II receptor blockade administered after injury improves muscle regeneration and decreases fibrosis in normal skeletal muscle

Bedair, HS and Karthikeyan, T and Quintero, A and Li, Y and Huard, J (2008) Angiotensin II receptor blockade administered after injury improves muscle regeneration and decreases fibrosis in normal skeletal muscle. American Journal of Sports Medicine, 36 (8). 1548 - 1554. ISSN 0363-5465

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Abstract

Background: Several therapeutic agents have been shown to inhibit fibrosis and improve regeneration after injury in skeletal muscle by antagonizing transforming growth factor-β1. Angiotensin receptor blockers have been shown to have a similar effect on transforming growth factor-β1 in a variety of tissues. Hypothesis: Systemic treatment of animals after injury of skeletal muscle with an angiotensin receptor blocker may decrease fibrosis and improve regeneration, mainly through transforming growth factor-β1 blockade, and can be used to improve skeletal muscle healing after injury. Study Design: Controlled laboratory study. Methods: Forty mice underwent bilateral partial gastrocnemius lacerations. Mice were assigned randomly to a control group (tap water), a low-dose angiotensin receptor blocker group (losartan, 0.05 mg/mL), or a high-dose angiotensin receptor blocker group (0.5 mg/mL). The medication was dissolved in tap water and administered enterally. Mice were sacrificed 3 or 5 weeks after injury, and the lacerated muscles were examined histologically for muscle regeneration and fibrosis. Results: Compared with control mice at 3 and 5 weeks, angiotensin receptor blocker-treated mice exhibited a histologic dose-dependent improvement in muscle regeneration and a measurable reduction in fibrous tissue formation within the area of injury. Conclusion: By modulating the response to local and systemic angiotensin II, angiotensin receptor blocker therapy significantly reduced fibrosis and led to an increase in the number of regenerating myofibers in acutely injured skeletal muscle. The clinical implications for this application of angiotensin receptor blockers are potentially far-reaching and include not only sports- and military-related injuries, but also diseases such as the muscular dystrophies and trauma- and surgery-related injury. Clinical Relevance: Angiotensin receptor blockers may provide a safe, clinically available treatment for improving healing after skeletal muscle injury. © 2008 American Orthopaedic Society for Sports Medicine.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Bedair, HS Karthikeyan, T Quintero, A Li, Y Huard, J
Centers:	Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date:	1 January 2008
Date Type:	Publication
Journal or Publication Title:	American Journal of Sports Medicine
Volume:	36
Number:	8
Page Range:	1548 - 1554
DOI or Unique Handle:	10.1177/0363546508315470
Schools and Programs:	School of Medicine > Orthopaedic Surgery
Refereed:	Yes
ISSN:	0363-5465
MeSH Headings:	Angiotensin II Type 1 Receptor Blockers--administration & dosage; Animals; Dose-Response Relationship, Drug; Fibrosis--drug therapy; Losartan--administration & dosage; Mice; Models, Animal; Muscle, Skeletal--injuries; Muscle, Skeletal--metabolism; Random Allocation
PubMed ID:	18550776
Date Deposited:	09 Apr 2014 15:36
Last Modified:	12 Jul 2019 22:55
URI:	http://d-scholarship.pitt.edu/id/eprint/21143

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