Document Detail

Absence of type VI collagen paradoxically improves cardiac function, structure, and remodeling after myocardial infarction.
MedLine Citation:
PMID:  22343710     Owner:  NLM     Status:  MEDLINE    
RATIONALE: We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this nonfibrillar collagen has not been explored in the setting of myocardial infarction (MI).
OBJECTIVE: To determine whether deletion of type VI collagen in an in vivo model of post-MI wound healing would alter cardiac function and remodeling in the days to weeks after injury.
METHODS AND RESULTS: Wild-type and Col6a1(-/-) mice were subjected to MI, followed by serial echocardiographic and histological assessments. At 8 weeks after MI, infarct size was significantly reduced, ejection fraction was significantly preserved (43.9% ± 3.3% versus 29.1% ± 4.3% for wild-type), and left ventricular chamber dilation was attenuated in the Col6a1(-/-) MI group (25.8% ± 7.9% increase versus 62.6% ± 16.5% for wild-type). The improvement in cardiac remodeling was evident as early as 10 days after MI in the Col6a1(-/-) mice. Myocyte apoptosis within the infarcted zones was initially greater in the Col6a1(-/-) group 3 days after MI, but by day 14 this was significantly reduced. Collagen deposition also was reduced in the infarcted and remote areas of the Col6a1(-/-) hearts. The reductions in chronic myocyte apoptosis and fibrosis are critical events leading to improved long-term remodeling and functional outcomes.
CONCLUSIONS: These unexpected results demonstrate for the first time that deletion of type VI collagen in this knockout model plays a critical protective role after MI by limiting infarct size, chronic apoptosis, aberrant remodeling, and fibrosis, leading to preservation of cardiac function.
Daniel J Luther; Charles K Thodeti; Patricia E Shamhart; Ravi K Adapala; Cheryl Hodnichak; Dorothee Weihrauch; Paolo Bonaldo; William M Chilian; J Gary Meszaros
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-16
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-05-10     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  851-6     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / physiology
Collagen Type VI / genetics*,  metabolism*
Disease Models, Animal
Extracellular Matrix / metabolism,  pathology
Fibrosis / genetics,  pathology,  physiopathology
Mice, Knockout
Myocardial Infarction / genetics*,  physiopathology*,  ultrasonography
Myocytes, Cardiac / pathology,  physiology
Ventricular Remodeling / physiology*
Grant Support
Reg. No./Substance:
0/Col6a1 protein, mouse; 0/Collagen Type VI

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE...
Next Document:  Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitiv...