IDIM 12530
INSTITUTO DE INVESTIGACIONES MEDICAS
Unidad Ejecutora - UE
artículos
Título:
Cardiac Thyrotropin Releasing Hormone (TRH) Mediates Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats (SHR).
Autor/es:
MARIANO L SCHUMAN; MARIA S LANDA; JORGE E TOBLLI; LUDMILA S PERES DIAZ; AZUCENA L ALVAREZ; SAMUEL FINKIELMAN; LEONARDO PAZ; GABRIEL CAO; CARLOS J PIROLA; SILVIA I GARCÍA
Revista:
HYPERTENSION
Editorial:
LIPPINCOTT WILLIAMS & WILKINS
Referencias:
Año: 2010 p. 103 - 109
ISSN:
0194-911X
Resumen:
Local thyrotropin releasing hormone (TRH) may be involved in cardiac pathophysiology, butits role in left ventricular hypertrophy (LVH) is still unknown.We studied whether local TRH is involved in LVH of spontaneously hypertensive rats (SHR)by investigating TRH expression and its long-term inhibition by interference RNA (TRHiRNA)during LVH development at two stages (prehypertrophy and hypertrophy).SHR and their control rats (WKY) were compared. Cardiac hypertrophy was expressed asheart/total body weight ratio (HW/BW). TRH content (RIA), preproTRH, TRH receptor typeI (TRHR1), BNP, and collagen mRNA expressions (real-timePCR) were measured. For longterm inhibition of TRH, TRH-iRNA was injected into the left ventricle (LV) wall for 8 weeks.Hearts were processed for morphometric studies and immunohistochemical analysis usingantibodies against α-smooth muscle actin, and collagen type III.LV preproTRH-mRNA abundance was similar in both strains at 7 weeks of age. At thehypertrophic stage (18 weeks old), however, there was a 15-fold increase in SHR vs. WKY,consistent with a significant increase of tripeptide levels and the expression of its receptor.Specific LV-TRH inhibition at the prehypertensive stage with TRH-iRNA, which decreased>50% preproTRH expression and tripeptide levels, prevented LVH development as shown bythe normal HW/BW ratio observed in TRH-iRNA-treated SHR. In addition, TRH-iRNAimpeded the increase of BNP and type III collagen expressions, and prevented the increase ofcardiomyocyte diameter evident in mismatch iRNA-treated adult SHR.These results show for the first time that the cardiac TRH system is involved in thedevelopment of LVH in SHR.
