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Beneficial actions of the natural triterpene oleanolic acid in an experimental model of myocarditis: a potential therapeutic role

AuthorsMartín, Rubén ; Hernández, Marita ; Cordova, Claudia; Muñoz, Juan Carlos; San Román, José Alberto; Cachofeiro, Victoria; Nieto, María Luisa
Issue Date2012
CitationESC Congress 2012
Abstract[Purpose]: Myocarditis and dilated cardiomyopathy represent the acute and chronic phases of an inflammatory disease of the myocardium, for which no standardized treatment is currently available. Oleanolic acid (OA), a natural triterpene widely distributed among higher plants, exhibits a variety of beneficial health properties. OA is found in numerous products of the Mediterranean diet, including olive oil, and is the major component of many traditional medicinal herbs. Several experimental approaches have shown its cardioprotective actions, and recently, it has been proven to be effective for the treatment of Th1 cell-mediated chronic inflammatory diseases, but its effect on inflammatory heart disorders has not been addressed yet. In this study, we investigated the effectiveness of OA in prevention-treatment of myocarditis in an experimental autoimmune model that mimics human myocarditis and dilated cardiomyopathy. [Methods and Results]: OA was administrated at the time (prophylactic, OA0) or 21 days (therapeutic, OA21) after disease induction in BALB/c mice with a myocardiogenic peptide. At days 21 or 65 post-immunization animals were sacrificed and both blood samples and hearts were collected. The levels of functional (BNP) and inflammation (Galectin-3, IL-17, IL-6, TNFα and IL-10) markers, as well as, IgG and IgM autoantibodies were detected by ELISAs. We found that, at both administration regimens, OA dramatically lessened the disease severity, which was characterized by a reduction in heart weight/body weight ratio and heart weight, indicating less myocardial edema, as well as a reduced BNP levels and lower anti-cardiac myosin IgG and IgM titers, compared with the group that received no drug. Histological analysis of the heart showed that OA significantly reduced the infiltration of inflammatory cells, fibrosis and calcium deposits, whereas such effect was not found in placebo-treated EAM mice. Furthermore, levels of the pro-inflammatory and profibrotic cytokines galectin- 3, IL-6, IL-17 and TNFα, in serum and heart tissue of the OA-treated EAM animals were significantly lower than of the vehicle-treated EAM mice, while anti-inflammatory IL-10 was markedly up-regulated. Collectively, these results suggest that OA ameliorates experimental autoimmune myocarditis by interfering with both the Th1/Th2/Th17 balance and the generation of cardiac-specific autoantibodies. [Conclusions]: OA may be considered a molecular switch for immune responses that improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.
DescriptionResumen del trabajo presentado al European Society of Cardiology Congress celebrado en Munich (Alemania) del 25 al 29 de agosto de 2012.
Appears in Collections:(IBGM) Comunicaciones congresos
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