Epicatechin as a Therapeutic Strategy to Mitigate the Development of Cardiac Remodeling and Fibrosis
Abstract
Heart failure (HF) is the most common cause of hospitalization for Medicare (i.e., older) patients. About half of patients suffer from a type of HF (weak pump function), for which there are multiple treatments. The other half of patients suffer from a form of HF where the heart cannot properly fill with blood. Currently, no treatments are available for patients with this type of HF, and studies demonstrate a female predominance of 2:1 vs. men, particularly in older patients. The causes for this high incidence in women remain unclear, but studies suggest that excess scar tissue may play a key role by making the heart much stiffer and thus be unable to properly fill with blood. Thus, there is a critical need to develop safe and effective treatments for preventing or reversing scar tissue formation in the heart. Flavonoids are a class of natural compounds found in cacao plants that are known for their safety profile, lack of toxicity, and health benefits. The consumption of cacao (i.e., cocoa) products reduces blood pressure and improves blood vessel function. Consumption of small amounts of cocoa/chocolate reduces cardiovascular risk including HF. We have identified a unique and potent ability of a cacao flavonoid called (-)-epicatechin (Epi) to reduce scar tissue formation in muscles. However, nothing is known about the effects of Epi in female animal models of stiffened (scarred) hearts. We propose to test the hypothesis that treatment with Epi will reduce heart scar tissue formation in animal models mimicking HF in women. We will examine three specific objectives as follows: Aim 1: Early use of Epi in female animal models of stiffened hearts in failure will prevent scar tissue formation and preserve function. For these purposes, we will use female rodent models of stiffening hearts that will receive Epi treatment. We will measure scar tissue formation and its impact on the function of the heart. Aim 2: Late use of Epi in female animal models of stiffened hearts in failure will reverse scar tissue formation and recover function. For these purposes, we will use female rodent models of pre-stiffened hearts that will receive Epi treatment. We will measure reductions in scar tissue and its impact on the function of the heart. Aim 3: The beneficial effects of Epi are due to their action on the heart cells that produce scar tissue. We will use the cell type that produces scar tissue in the heart and determine the manner by which Epi treatment can block its formation. Currently, there is no treatment for patients with a type of HF that is associated with stiffer heart tissue, which most notably impacts women. We propose to explore the preventive and therapeutic potential of Epi to reduce tissue scar formation in the heart and lead to improved function. The gathering of this type of evidence for Epi effects will serve the purpose of moving ahead with the planning of studies in patients suffering from this disease, once the treatment is approved by the Food and Drug Administration.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610244
Entities
People
- Francisco Villarreal
Organizations
- United States Army
- University of California, San Diego