Beta2-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation

Pablo Aránguiz-Urroz, Jimena Canales, Miguel Copaja, Rodrigo Troncoso, Jose Miguel Vicencio, Constanza Carrillo, Hernán Lara, Sergio Lavandero, Guillermo Díaz-Araya

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

Abstract

Autophagy is a physiological degradative process key to cell survival during nutrient deprivation, cell differentiation and development. It plays a major role in the turnover of damaged macromolecules and organelles, and it has been involved in the pathogenesis of different cardiovascular diseases. Activation of the adrenergic system is commonly associated with cardiac fibrosis and remodeling, and cardiac fibroblasts are key players in these processes. Whether adrenergic stimulation modulates cardiac fibroblast autophagy remains unexplored. In the present study, we aimed at this question and evaluated the effects of b2-adrenergic stimulation upon autophagy. Cultured adult rat cardiac fibroblasts were treated with agonists or antagonists of beta-adrenergic receptors (b-AR), and autophagy was assessed by electron microscopy, GFP-LC3 subcellular distribution, and immunowesternblot of endogenous LC3. The predominant expression of b2-ARs was determined and characterized by radioligand binding assays using [3H]dihydroalprenolol. Both, isoproterenol and norepinephrine (non-selective b-AR agonists), as well as salbutamol (selective b2-AR agonist) increased autophagic flux, and these effects were blocked by propanolol (b-AR antagonist), ICI-118,551 (selective b2-AR antagonist), 3-methyladenine but not by atenolol (selective b1-AR antagonist). The increase in autophagy was correlated with an enhanced degradation of collagen, and this effect was abrogated by the inhibition of autophagic flux. Overall, our data suggest that b2-adrenergic stimulation triggers autophagy in cardiac fibroblasts, and that this response could contribute to reduce the deleterious effects of high adrenergic stimulation upon cardiac fibrosis.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • Beta adrenergic receptor
  • Catecholamine isoproterenol norepinephrine propanolol salbutamol ICI-118,551 dihydroalprenolol
  • Heart failure cardiac fibrosis remodeling
  • LC3 macroautophagy lysosome autophagy LAMP1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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