Angiotensin II Requires an Intact Cardiac Thyrotropin-Releasing Hormone (TRH) System to Induce Cardiac Hypertrophy in Mouse.

PERES DIAZ, LUDMILA S; SCHUMAN, MARIANO LUIS; AISICOVICH MAIA; TOBLLI, J; PIROLA, CARLOS JOSE; LANDA, MARIA SILVINA; GARCIA , SILVIA INES

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2018 vol. 114 p. 1 - 11

0022-2828

Cardiactyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied leftventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibitionprevents both hypertrophy and fibrosis. In a normal heart, the TRH increaseinduces fibrosis and hypertrophy opening the question of whether TRH could be acommon mediator of left ventricular hypertrophy (LVH). We used angiotensin II (AngII)as an inductor of LVH to evaluate if the blockade of LV-TRH  prevents hypertrophy and fibrosis in mice. Wechallenged C57BL/6 adult male mice with an infusion of  AngII (osmotic pumps; 2 mg/kg.day) to induceLVH. Groups of mice were injected with an intracardiac siRNA-TRH or scrambledsiRNA (siRNA-Con). Body weight, water intake and systolic arterial bloodpressure (SABP) were measured daily. AngII significantly increased water intakeand SABP (p<0.05). Cardiac hypertrophy (heart weight/body weight) wasevident in the group with the normal cardiac TRH system. In fact, it was found anAngII-induced increase of TRH precursor mRNA (p<0.05) in conjunction withelevated TRH levels measured by immunohistochemistry and western blot. Thesechanges were not observed in the AngII + siRNA-TRH group. Furthermore, AngIIincreased significantly (p<0.05) BNP (hypertrophic marker), collagens I andIII and TGF-β (fibrosis markers) expression in the group with the nativecardiac TRH system. These increases were attenuated in the groups with the TRHsystem blocked despite the high blood pressure. Similar and stronger results were observed ?in vitro? with NIH3T3 andH9C2 cell culture models, where, when the TRH system is blocked, AngII stimuluswas not able to induce the markers of its fibrotic and hypertrophic effects, sowe believe that these effects are independent of any other physiologicalmodifications.Our results point out thatcardiac TRH is required for AngII-induced hypertrophic and fibrotic effects.