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Abstract

In various models of cardiac hypertrophy, e.g. treatment of rats with norepinephrine infusion or pressure overload, increased expression of cytokines together with increase in extracellular matrix proteins (ECMP) was reported. In this study the effect of triiodothyronine (T3) on the expression of mRNA for cytokines and ECMP was investigated. Female Sprague-Dawley rats were treated daily with T3 in a dose of 0.2 mg x kg(-1) of body weight s.c. Changes in the left (LV) and right (RV) ventricular function were measured 6, 24, 48, 72 h and 7 and 14 days after the first T3-injection using Millar ultraminiature pressure catheter transducers. RNA was isolated from LV and RV tissue, and the expression of cytokines and ECMP was measured using the ribonuclease protection assay. T3-treatment induced a significant increase in LV dP/dtmax and RV dP/dtmax, (p < 0.05) 24 h after the first injection of T3 together with an increase in heart rate (p < 0.01). The RV systolic pressure increased 48 h after the first T3 injection, whereas the LV systolic pressure remained unchanged. After 48 h the heart weight to body weight ratio was increased (p < 0.01). Hypertrophy of the RV was more prominent than that of the LV (155.9 vs. 137.7%). In all groups the expression of mRNA for interleukins (IL) IL-6, IL-1beta, IL-1alpha and tumour necrosis factor (TNF)-alpha in both ventricles did not change (p > 0.05). There was a significant increase in the mRNA for colligin 24 h after the T3 injection in both LV (p < 0.01) and RV (p < 0.05). This was followed by an increase in the mRNA for collagen I and III 72 h after the first T3-dose (p < 0.05 in RV; p < 0.01 in LV). At this point, the mRNA for tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) was increased (p < 0.01) in the LV only. Moreover, after 7 days also the mRNA for matrix metalloproteinase (MMP)-2 increased (p < 0.01) in the LV. Both, TIMP-2 and MMP-2 were increased in the RV only after 14 days (p < 0.05). The gelatinase activity of MMP-2, however, was unchanged in both ventricles. The T3-induced cardiac hypertrophy was not accompanied by fibrosis as measured by the Sirius red staining after 14-days of T3-treatment. The moderate increase in mRNA for ECMP and MMP may be attributed more to the increasing mass of the ventricles with the accompanying remodelling of the ECM than to increased fibrosis.

Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

“…No report can be found regarding the effects of THs on MMPs and TIMPs expression in the non-infarcted area during late stage post-MI LV remodeling. However, Ziegelhoffer-Mihalovicova et al reported that T3-induced cardiac hypertrophy was not accompanied by cardiac fibrosis but an increase in MMP-2 and TIMP-2 expression [40]. Ghose Roy et al found a reduction in collagen I and III in cardiac tissue with an increase in MMP-1 activity and a decrease in TIMP-3 and TIMP-4 expression in T3-induced cardiac hypertrophy [30].…”

Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling

“…Most studies on the cardiovascular effects of thyroid hormones have particularly targeted left ventricular improvement. Nonetheless, little is known about the effect of an excess or deficiency of thyroid hormones on the myocardium collagen gene and the responsiveness of interstitial cells to these hormones [89] , [90] , [91] . One study, however, showed that long term hypothyroidism caused overall cardiac muscle stiffness and left ventricle diastolic wall thickness due to increased collagen I/III-based stiffness [92] .…”

New Insights into Mechanisms of Cardioprotection Mediated by Thyroid Hormones

“…It has been reported that mRNA for collagen type I, the major fibrillar collagen in the heart, is downregulated by TH treatment both in the myocardium and in CF culture [55]. In similar experiments TH-induced hypertrophy is accompanied by an increase of MMP1, MMP2, and TIMP2 without signs of cardiac fibrosis or inflammatory response [56, 57]. T3 can also repress the activation of some transcription factors such as activator protein 1 (AP-1) [58, 59] that are involved in activation of MMPs and collagen gene expression [60].…”