Epicatechin as a Therapeutic Strategy to Mitigate the Development of Cardiac Remodeling and Fibrosis
Abstract
Heart failure with preserved ejection fraction (HFpEF) continues to increase and little is known about its pathophysiology. About 2/3 of patients are women and risk factors include aging, hypertension and metabolic syndrome. A feature of the disease is cardiac fibrosis. Currently, no drugs target HFpEF and the development of animal models can assist in therapy evaluation. We developed a female rat model of aging, estrogen depletion and metabolic syndrome to evaluate the role of these factors in altering cardiac structure/function. Aged female Fischer F344 rats were allocated into an aging group, aging + ovariectomy and aging + ovariectomy + 10% fructose in drinking water. At 22 months of age, animals were anesthetized and left ventricular (LV) function was evaluated. Histological measures were also obtained. Hemodynamic analysis evidenced decreases in stroke work, cardiac output and diastolic function with ovariectomy +/- fructose. In Plasma inflammatory cytokines increased. Histological analysis indicated inflammatory infiltration, papillary muscle and interstitial fibrosis. Late stage treatment for 1 month with (-)-epicatechin (Epi) of rats with ovariectomy and fructose led to right shifted LV pressure-volume curves, reduced cytokines and fibrosis. However, no changes in contractile function were detected. In vitro studies using cardiac fibroblasts yielded increases in collagen production with high glucose media an effect blocked by Epi via reduced TGF-b1 levelsand associated signaling pathway. Thus, Epi has the potential to diminish fibrosis in aged myocardium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1128311
Entities
People
- Francisco Villarreal
Organizations
- University of California