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).