Sustained augmentation of cardiac alpha1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes

Journal of Molecular and Cellular Cardiology
Hervé ChauletRobert M Graham

Abstract

We previously reported that transgenic (TG) mice with cardiac-restricted alpha(1A)-adrenergic receptor (alpha(1A)-AR)-overexpression showed enhanced contractility, but no hypertrophy. Since chronic inotropic enhancement may be deleterious, we investigated if long-term, cardiac function and longevity are compromised. alpha(1A)-TG mice, but not their non-TG littermates (NTLs), showed progressive loss of left ventricular (LV) hypercontractility (dP/dt(max): 14,567+/-603 to 11,610+/-915 mmHg/s, P<0.05, A1A1 line: 170-fold overexpression; and 13,625+/-826 to 8322+/-682 mmHg/s, respectively, P<0.05, A1A4 line: 112-fold overexpression, at 2 and 6 months, respectively). Both TG lines developed LV fibrosis, but not LV dilatation or hypertrophy, despite activation of hypertrophic signaling pathways. Microarray and real time RT-PCR analyses revealed activation of matricellular protein genes, including those for thrombospondin 1, connective tissue growth factor and tenascin C, but not transforming growth factor beta1. Life-span was markedly shortened (mean age at death: 155 days, A1A1 line; 224 days, A1A4 line compared with NTLs: >300 days). Telemetric electrocardiography revealed that death in the alpha(1A)-AR TG mice was due to cardiac s...Continue Reading

Citations

Mar 14, 2014·Pflügers Archiv : European journal of physiology·Anthony J Baker
Oct 3, 2009·Journal of Cell Communication and Signaling·Mark W M SchellingsStephane Heymans
Nov 19, 2009·Circulation. Heart Failure·Brian C JensenPaul C Simpson
Feb 23, 2008·Clinical and Experimental Pharmacology & Physiology·Xiao-Jun Du
Jul 25, 2007·Clinical and Experimental Pharmacology & Physiology·Elizabeth A Woodcock
Oct 30, 2012·Expert Opinion on Therapeutic Targets·David R Soto-PantojaDavid D Roberts
Nov 11, 2008·Annals of the New York Academy of Sciences·Riccardo RuffoliFrancesco Fornai
Apr 27, 2012·Physiological Reviews·Nikolaos G Frangogiannis
Mar 27, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Hélène ThibaultGeneviève Derumeaux
Feb 23, 2011·Journal of Receptor and Signal Transduction Research·Dianne M Perez, Van A Doze
Jan 20, 2017·BioMed Research International·Peng XiaZhaokang Cheng
Dec 5, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jiandong ZhangBrian C Jensen
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Dianne M Perez
Dec 2, 2010·Journal of Molecular and Cellular Cardiology·Brian C JensenPaul C Simpson

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