Heart valve disease models
The information regarding the role of MR in cardiac valve physiology or pathology is scarce. The lack of relevant experimental models of human valve diseases makes it difficult to study the potential benefits of pharmacological treatments. In the context of aortic valve diseases, spironolactone reduced myocardial fibrosis and LV mass in rodents with chronic aortic regurgitation, although aortic valve alterations have not been explored (Adnane Zendaoui et al., 2012). In a model of aortic stenosis-induced chronic LV pressure-overload, early administration of spironolactone unexpectedly increased cardiac hypertrophy and dilation, and impaired LV function (Okoshi et al., 2016).
Anorectic compounds, including nordexfenfluramine (NDF) that interact with the serotonergic system by targeting 5-HT2 (5-hydroxytryptamine receptor) receptor subtypes have been associated with fibromyxomatous remodeling of the mitral valve (HM et al., 1997). Pharmacological intervention using spironolactone prevented the increase in the area and thickness of mitral valve leaflets, as well as the increased expression of mitral valve proteoglycans in NDF-treated mice (Ibarrola et al., 2020b). Moreover, spironolactone also exerted beneficial effects in myocardium by reducing fibrosis (Ibarrola et al., 2020a). In accordance with these findings, the addition of spironolactone to conventional therapy increased survival compared with treatment with conventional therapy alone in dogs with naturally occurring myxomatous mitral valve disease (Bernay et al., 2010).