GSE151695 Type V collagen in scar tissue regulates the size of scar after heart injury

In this report, we demonstrate that collagen V, a fibrillar collagen and a minor constituent of heart scars regulates the size of heart scars after ischemic cardiac injury. Depletion of collagen V in heart scars in two independent animal models led to a significant and paradoxical increase in post infarction scar tissue size with worsening of heart function. A systems genetics approach analyzing genes versus traits across 100 in-bred strains of mice independently demonstrated that collagen V is a critical driver of post injury heart function. We show that collagen V deficiency alters the ultra-structure and mechanical properties of scar tissue that make it more vulnerable to expansion. There is altered reciprocal feedback between matrix and cells that induce expression of specific mechanosensitive integrins which drive fibroblast activation and increased ECM gene expression. Scar size increases. Administration of cilengitide, an inhibitor of specific integrins, completely rescues the phenotype of increased post injury scarring, myofibroblast formation and cardiac dysfunction in collagen V deficient mice. These observations demonstrate that collagen V, a structural constituent of heart scar tissue regulates scar size in an integrin dependent manner.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research