title: Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit.
abstract: Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition. It is unclear whether these alterations reflect very severe hemodynamic derangement or are a component of mild hypertrophic stress. Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), myosin isoforms, myofibrillar ATPase activity, and left ventricular (LV) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hypertension caused by 12 weeks of cellophane wrap of the kidneys (n=12). LV/body weight ratio increased by 28% in LVH compared to shams (P<0.001); no animals had evidence of HF. In LVH, the percentage of TnT2 was modestly but significantly increased compared to shams [6.2+/-1.9 (+/-S.D. ) v 3.7+/-1.0%, P<0.05], mainly as a consequence of a parallel decrease in TnT4 (P=0.07). Sham hearts ranged from 75-100% V3 isomyosin, whereas all LVH hearts had 100% of the V3 form. There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates. The slope of the VO2-pressure-volume-area relation (a measure of the energy conversion efficiency of the contractile machinery) was also unchanged. We conclude that in the rabbit, shifts in TnT isoforms toward a more "fetal" pattern occur during mild LVH and, therefore, are likely to be a general feature of the response to hemodynamic stress, rather than a phenomenon confined to end-stage disease. These modest shifts are not associated with major alterations in LV myofibrillar ATPase activity or mechanoenergetics.
authors.affiliation: Cardiology Unit, Department of Molecular Physiology and Biophysics, The University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Higashiyama
authors.forename: H
authors.initials: H
authors.lastname: Yaku
authors.forename: S
authors.initials: S
authors.lastname: Bell
authors.forename: J
authors.initials: J
authors.lastname: Fabian
authors.forename: M W
authors.initials: MW
authors.lastname: Watkins
authors.forename: D J
authors.initials: DJ
authors.lastname: Schneider
authors.forename: D W
authors.initials: DW
authors.lastname: Maughan
authors.forename: M M
authors.initials: MM
authors.lastname: LeWinter
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D014336:Troponin / Q000378:metabolism*; D020107:Troponin T
chemical_list: D014336:Troponin; D020107:Troponin T; D000251:Adenosine Triphosphatases; D009218:Myosins