Effect of a Cleavage-Resistant Collagen Mutation on Left Ventricular Remodeling

ABSTRACT—Matrix metalloproteinase–mediated degradation of type I collagen may play a role in cardiac remodeling after strain or injury. To explore this hypothesis, we used mice homozygous (r/r) for a targeted mutation in Col1a1; these mice synthesize collagen I that resists collagenase cleavage at G...

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Bibliographic Details
Published in:Circulation research 2003-08, Vol.93 (3), p.238-245
Main Authors: Lindsey, Merry L, Yoshioka, Jun, MacGillivray, Catherine, Muangman, Suphichaya, Gannon, Joseph, Verghese, Anjali, Aikawa, Masanori, Libby, Peter, Krane, Stephen M, Lee, Richard T
Format: Article
Language:English
Subjects:
Animals
Aorta - pathology
Biological and medical sciences
Cardiology. Vascular system
Cardiomegaly - genetics
Cardiomegaly - pathology
Collagen - genetics
Collagen - metabolism
Constriction, Pathologic - pathology
Coronary heart disease
Crosses, Genetic
Disease Models, Animal
Disease Progression
Echocardiography
Endopeptidases - metabolism
Fibrosis - complications
Fibrosis - pathology
Heart
Hemodynamics
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mutation
Myocardial Infarction - complications
Myocardial Infarction - pathology
Myocardium - metabolism
Myocardium - pathology
Space life sciences
Survival Rate
Ventricular Remodeling - genetics
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Summary:ABSTRACT—Matrix metalloproteinase–mediated degradation of type I collagen may play a role in cardiac remodeling after strain or injury. To explore this hypothesis, we used mice homozygous (r/r) for a targeted mutation in Col1a1; these mice synthesize collagen I that resists collagenase cleavage at Gly975-Leu976. A total of 64 r/r and 84 littermate wild-type mice (WT) underwent experimental pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI). Echocardiographic, hemodynamic, and histological parameters were evaluated up to 12 weeks after TAC or 21 days after MI. At 4 weeks after TAC, collagen levels, wall thickness, and echocardiographic parameters were similar in the 2 groups. At 12 weeks after TAC, r/r mice had smaller LV dimensions (ESD2.7±0.2 mm WT versus 1.7±0.2 mm r/r, P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000085580.45279.60