Thyroid hormone induces myocardial matrix degradation by activating matrix metalloproteinase-1.
Hyperthyroid patients develop left ventricular hypertrophy associated with alterations of several cardiac parameters such as heart rate, cardiac output, cardiac contraction and hemodynamic overload leading to cardiac complications. Although cardiac hypertrophy and contractile abnormality occur, interstitial fibrosis in the heart usually does not take place in hyperthyroid condition. Therefore, in the present study, the mechanism regulating myocardial extracellular matrix (ECM) remodeling in hyperthyroid condition was investigated. Cardiac hypertrophy was developed in Sprague-Dawley rats by administration of 3,5,3'-triiodo-L-thyronine (triiodothyronine, 8 microg/100g BW, ip, SID) and glucocorticosteroid, dexamethasone (DEX, 35 microg/100g BW, po, SID), which is also an inducer of hypertrophy for 15 days. Heart/Body weight ratio and atrial and brain natriuretic peptide mRNAs were significantly increased in both triiodothyronine- and DEX-treated rats compared to control. Collagens-I and -III deposition in the left ventricular sections was reduced in triiodothyronine-treated rats, whereas in DEX-treated animals those were increased compared to control. While mRNA and protein levels of procollagens-I and -III were increased with triiodothyronine (p<0.01), the levels of mature collagens-I and -III were decreased. The levels of the mature collagens were increased with DEX compared to control. MMP-1 activity in the serum and left ventricle was higher with reduced levels of TIMPs-3 and -4 in the left ventricle of triiodothyronine-treated rats. The results suggest that accelerated breakdown of collagens-I and -III by MMP-1 due to suppression of the endogenous TIMPs plays an important role in regulating the ECM in myocardium of hyperthyroid rat.
Ghose Roy
Sreerupa
S
Molecular Endocrinology Laboratory, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.
Mishra
Sumita
S
Ghosh
Goutam
G
Bandyopadhyay
Arun
A
D000818:Animals; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009119:Muscle Contraction; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism / Q000502:physiology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
D003094:Collagen; D003907:Dexamethasone; D020781:Matrix Metalloproteinase 1; D013963:Thyroid Hormones; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D014284:Triiodothyronine; D000097792:Tissue Inhibitor of Metalloproteinase-4