Thyroid hormone analog, diiodothyropropionic acid (DITPA), exerts beneficial effects on chamber and cellular remodeling in cardiomyopathic hamsters.
Diiodothyropropionic acid (DITPA) is a thyroid hormone analog that is currently in phase II clinical trials. However, there have not been any studies to comprehensively analyze its effect on myocyte morphology. In addition, long-term studies with DITPA have not been done. This study compares the effects of DITPA with L-thyroxine (T4) on chamber remodeling, cardiac function, cellular morphology, cardiac blood flow, and protein expression. Normal and cardiomyopathic hamsters were treated with T4 or DITPA for 2 months. At the end of the treatment, echos, hemodynamics, coronary blood flow, cell morphology, and protein expression data were collected. Both T4 and DITPA treatment reduced chamber diameter during diastole, suggesting attenuated chamber dilatation in cardiomyopathic hamsters. Wall thickness also tended to increase, which was supported by cell morphology data in which DITPA significantly increased cross-sectional growth of myocytes specifically in the minor dimension, which is oriented transmurally. T4 and DITPA also increased myocardial blood flow both at baseline and after maximal dilation. This suggests there was increased angiogenesis or reduced loss of arterioles. Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply.
Kuzman
James A
JA
Cardiovascular Research Institute, Sanford Research, University of South Dakota, 1100 East 21st Street, Sioux Falls, SD 57105, USA.
Tang
Yida
Y
Vogelsang
Kathryn A
KA
Said
Suleman
S
Anderson
Brent E
BE
Morkin
Eugene
E
Gerdes
A Martin
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D006224:Cricetinae; D004104:Diiodothyronines / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D011422:Propionates / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects*
D002316:Cardiotonic Agents; D004104:Diiodothyronines; D011422:Propionates; D014284:Triiodothyronine; C082182:3,5-diiodothyropropionic acid; D013972:Thyrotropin; D013974:Thyroxine