title: Thyroid hormone receptor-α deletion decreases heart function and exercise performance in apolipoprotein E-deficient mice.
abstract: The deletion of thyroid hormone receptor-α (TRα) in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice (ApoE(-/-)TRα(0/0)) accelerates the formation of atherosclerotic plaques without aggravation of hypercholesterolemia. To evaluate other predisposition risk factors to atherosclerosis in this model, we studied blood pressure (BP) and cardiac and vascular functions, as well as exercise tolerance in young adult ApoE(-/-)TRα(0/0) mice before the development of atherosclerotic plaques. Telemetric BP recorded for 4 consecutive days showed that the spontaneous systolic BP was slightly decreased in ApoE(-/-)TRα(0/0) compared with ApoE(-/-) mice associated with a reduced locomotor activity. The percentage of animals that completed endurance (57% vs. 89%) and maximal running (0% vs. 89% at 46 cm/s speed in ApoE(-/-)TRα(0/0) and ApoE(-/-) mice, respectively) tests was lower in ApoE(-/-)TRα(0/0) mice. Moreover, during the maximal running test, both maximal running speed and running distance were significantly reduced in ApoE(-/-)TRα(0/0) mice, associated with a blunted BP response to exercise. Transthoracic echocardiography revealed a decreased interventricular septum thickness and an increased end-systolic left ventricular volume in ApoE(-/-)TRα(0/0) mice. Accordingly, left ventricular fractional shortening, ejection fraction, and stroke volume were all significantly decreased in ApoE(-/-)TRα(0/0) mice with a concomitant blunted cardiac output. No interstrain difference was observed in vascular reactivity, except that ApoE(-/-)TRα(0/0) mice exhibited an enhanced acetylcholine-induced relaxation in mesenteric and distal femoral arteries. In conclusion, the deletion of TRα in ApoE(-/-) mice alters cardiac structure and contractility; both could contribute to blunted BP response to physical exercise and impaired exercise performance.
authors.affiliation: Neurocardiology Unit - EA 4612, Institute of Pharmaceutical and Biological Sciences, University Claude Bernard Lyon 1, Lyon, France; klliu@univ-lyon1.fr.
authors.forename: Kiao Ling
authors.initials: KL
authors.lastname: Liu
authors.affiliation: Institute of Functional Genomics of Lyon, University Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; and.
authors.forename: Laurence
authors.initials: L
authors.lastname: Canaple
authors.affiliation: Technical Platform ANIPHY, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Del Carmine
authors.affiliation: Institute of Functional Genomics of Lyon, University Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; and.
authors.forename: Karine
authors.initials: K
authors.lastname: Gauthier
authors.affiliation: Neurocardiology Unit - EA 4612, Institute of Pharmaceutical and Biological Sciences, University Claude Bernard Lyon 1, Lyon, France; Technical Platform ANIPHY, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Beylot
authors.affiliation: Neurocardiology Unit - EA 4612, Institute of Pharmaceutical and Biological Sciences, University Claude Bernard Lyon 1, Lyon, France;
authors.forename: Ming
authors.initials: M
authors.lastname: Lo
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D001794:Blood Pressure; D001823:Body Composition; D002940:Circadian Rhythm; D004452:Echocardiography; D017353:Gene Deletion; D006321:Heart / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D012420:Running; D013318:Stroke Volume; D013599:Systole; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D037021:Thyroid Hormone Receptors alpha
keywords: apolipoprotein E-deficient mice; cardiac function; exercise performance; thyroid hormone receptor-α; vascular reactivity