The expression of mRNA of cytokines and of extracellular matrix proteins in triiodothyronine-treated rat hearts.
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.
Ziegelhöffer-Mihalovicová
Barbara
B
Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. zieb@medizin.uni-leipzig.de
Briest
Wilfried
W
Baba
Hideo A
HA
Rassler
Beate
B
Zimmer
Heinz-Gerd
HG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000187:drug effects / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006023:Glycoproteins; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000187:drug effects / Q000235:genetics; D014284:Triiodothyronine / Q000009:adverse effects / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
D002352:Carrier Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; C046289:colligin; D014284:Triiodothyronine; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2