TYPE 5 collagen plays a crucial role in regulating scar tissue size in the heart and may explain why certain individuals experience more extensive scarring compared to others, following a heart attack.
“Two individuals with the same degree of heart attack can end up with different amounts of scar tissue,” said senior study author Dr Arjun Deb, Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. Scar tissue is formed when fibroblasts secrete collagens, which were analysed to assess why some hearts scar more than others.
The uninjured heart predominantly expresses Type 1 and 3 collagens, which make up approximately 97% of scar tissue; however, during their research, the team detected that Type 5 collagen, which is not found in the uninjured heart, was abundantly expressed in scar tissue. A mouse model, genetically engineered to be incapable of producing Type 5 collagen in scar tissue following heart injury, was used to determine the role of Type 5 collagen in scarring. Results showed that the deletion of the collagen resulted in a 50% increase in scar size. Dr Deb stated: “Scar tissue without type 5 collagen is compliant like rubber. So, when the heart fills with blood, the scar tissue expands in much the same way as a rubber balloon expands when it is filled with air.” He further noted that Type 5 collagen regulates the stiffness of scar tissue and, without it, fibroblasts secrete more collagen to reinforce the scar and prevent expansion. Without Type 5 collagen, the cycle of expansion and scar growth continues.
Differences in Type 5 collagen expression might be the underlying cause of scar size variation between heart attack survivors. Cilengitide, a selective integrin inhibitor, was found to disrupt the expansion cycle and reduce scar size in Type 5 collagen-deficient mice. Cilengitide has not yet been tested as a treatment option for increased scarring in humans; however, the team is currently working on a test that could identify individuals who produce less Type 5 collagen and may benefit from cilengitide treatment.