Novel Collagen-Based Inflammatory Mediators of Cardiomyopathy
Abstract
Reductions in plasma/tissue ascorbate levels due to environmental conditions and/or diet could cause fibroblasts to secrete procollagens as atypical hyperglycosylated forms. Resultant inflammatory events could cause ischemic heart disease and/or aortic stenosis, which can lead to dilated and hypertrophic cardiomyopathies. We proposed to test this hypothesis using cell culture experiments and mouse models. In the in vivo mouse work, we produced our experimental mice and completed the proposed ascorbate treatment/starvation regimens but were unable to find cardiovascular effects via echocardiography or aortic staining. The lack of an effect may have been caused by low levels of ascorbate in the food during the ascorbate off cycle. In the in vitro work, we were unsuccessful purifying hyperglycosylated procollagen but did identify O-glycosylated procollagens by Click-iT chemistry, and determined that only PLOD2 knockdown led to noticeable changes in electrophoretic mobility indicative of post-translational procollagen modifications.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1223179
Entities
People
- Randy T. Cowling
Organizations
- University of California, San Diego