β2-Adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis

Xiao Jun Du, Dominic J. Autelitano, Rodney J. Dilley, Binghui Wang, Anthony M. Dart, Elizabeth A. Woodcock

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108 Citations (Scopus)

Abstract

Background -β Adrenergic signaling is downregulated in the failing heart, and the significance of such change remains unclear. Methods and Results - To address the role of β-adrenergic dysfunction in heart failure (HF), aortic stenosis (AS) was induced in wild-type (WT) and transgenic (TG) mice with cardiac targeted overexpression of β2-adrenergic receptors (ARs), and animals were studied 9 weeks later. The extents of increase in systolic arterial pressure (P<0.01 versus controls), left ventricular (LV) hypertrophy (TG, 94±6 to 175±7 mg; WT, 110±6 to 168± 10 mg; both P<0.01), and expression of ANP mRNA were similar between TG and WT mice with AS. TG mice had higher incidences of premature death and critical illness due to heart failure (75% versus 23%), pleural effusion (81% versus 45%), and left atrial thrombosis (81% versus 36%, all P<0.05). A more extensive focal fibrosis was found in the hypertrophied LV of TG mice (P<0.05). These findings indicate a more severe LV dysfunction in TG mice. In sham-operated mice, LV dP/dt(max) and heart rate were markedly higher in TG than WT mice (both P<0.01). dP/dt(max) was lower in both AS groups than in sham-operated controls, and this tended to be more pronounced in TG than WT mice (-32±5% versus - 16±6%, P=0.059), although dP/dt(max) remained higher in TG than WT groups (P<0.05). Conclusions - Elevated cardiac β-adrenergic activity by β2-AR overexpression leads to functional deterioration after pressure overload.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalCirculation
Volume101
Issue number1
DOIs
Publication statusPublished - 4 Jan 2000
Externally publishedYes

Keywords

  • Genetics
  • Heart failure
  • Hypertrophy
  • Pressure
  • Receptors, adrenergic, beta

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