Novel Collagen-Based Inflammatory Mediators of Cardiomyopathy
Abstract
Cardiomyopathies are diseases that affect up to 1 in 500 Americans, where the heart muscle cannot function properly. Patients with cardiomyopathies are at increased risk of hospitalization and death from heart failure. Dilated cardiomyopathy is the most common cardiomyopathy that develops in adults, and ischemic heart disease (where blood supply to the heart is restricted) is the most common cause of dilated cardiomyopathy. Cholesterol-lowering drugs have reduced deaths from ischemic heart disease. However, many patients with ischemic heart disease do not have high cholesterol. Therefore, there must be other reasons for developing this disease, and fully understanding these reasons is important to prevent and/or treat this disease effectively in all people. Ischemic heart disease is believed to start in small areas of inflammation on the inner surface of blood vessels, although the reasons for this are still unclear. Unlike most animals, humans can no longer make their own vitamin C and we must obtain it in our diets. Long-term lack of vitamin C leads to scurvy, which has been associated with ischemic heart disease. However, the connection between vitamin C and ischemic heart disease has been nearly forgotten because of improved nutrition and the fact that scurvy can take weeks to months to develop after vitamin C deficiency. It has been shown previously that, in the absence of vitamin C, unusually modified collagens can be made by cells. We hypothesize that this unusual collagen can cause inflammation, leading to blood vessel damage much earlier after vitamin C deficiency than originally believed. This hypothesis is highly innovative, having the potential to expand our understanding of what can lead to devastating cardiomyopathies. We propose to test this hypothesis in the grant by using isolated mammalian cells that can be studied in culture and by using mice that have been genetically mutated to require vitamin C in their diet, like humans. In addition to examining the heart and blood vessels of these mice, we will examine their heart valves because the inflammation that occurs in the blood vessels is believed to occur also in the heart valves.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010091
Entities
People
- Randy T. Cowling
Organizations
- United States Army
- University of California, San Diego