THE CARDIAC HYPERTROPHY OF THE OBESE AGOUTI MICE IS NOT DUE TO HYPERTENSION: ROLE OF THE CARDIAC TRH SYSTEM

LUDMILA S PERES DIAZ; MAIA AISICOVICH; MARIANO L. SCHUMAN; JORGE E TOBLLI; MARÍA S. LANDA; SILVIA I. GARCÍA

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Cardiac TRH (cTRH) is overexpressed in SHR left ventricle. Specific TRH-iRNA treatment induced downregulation of LV-TRH production, preventing cardiac hypertrophy and fibrosis demonstrating that TRH is involved in hypertrophy associated with hypertrophic and fibrotic processes. We confirmed TRH hypertrophy and fibrotic effects in myocytes and fibroblasts. We showed that cTRH participates in the AII-induced hypertrophy mice model. On the other hand, we described the TRH-leptin interaction in the nervous system where leptin induces TRH gene suggesting that this interaction could function also in the heart. Hyperleptinemic obese models present hypertension and hypertrophy, primarily attributable to high pressure. In contrast, we hypothetized that in obese agouti mice (AG) cardiac alterations could be provoked by high leptin levels which could interact with leptin receptors thereby inducing a cTRH increase. Indeed, in AG obese adult males n=10 we confirmed obese phenotype through the increase (p<0.01) of body weight, blood pressure, leptin levels and cardiac hypertrophy index in the AG vs lean C57. As thought AG shows 3-fold TRH expression increase (PCR) confirmed by IHC suggesting that heart alterations could be induced by cTRH. Indeed AG hearts showed higher (p<0.01) BNP, BMHC and col III expression confirmed by Masson. Then, we treated an AG group (n=12) with the diuretic hydrochlorotiazide (AG+HC) from 2 to 18w.Treatment was effective as AG+HC presented similar pressure vs lean C57 but lower than AG obese (p<0.01) without effect on body weight.Although normal blood pressure AG+HC presented higher hypertrophy index similar to AG mice with higher cTRH expression accompanied byan increase (p<0.01) in hypertrophy markers and fibrosis (BNP, BMHC, Col III) pointing out that in obesity, cardiac hypertrophyis independent of hypertension, opening the possibility that high leptin evokes cTRH induction responsible for AG obesity-induced cardiac alterations.