CELLULAR MECHANISMS OF ANGIOTENSIN II TYPE-2 RECEPTOR ACTIVATION IN PROTECTING AGAINST CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Abstract

Chronic obstructive pulmonary diseases (COPD) is a major medical problem and huge economic burden to the society. COPD is characterized by airway inflammation, airway remodeling, and emphysematic destruction of the peripheral airways. The effects of AT2R activation by an AT2R-selective potent agonist compound 21 (C21) were evaluated in cigarette smoking (CS)-induced mouse acute and chronic COPD models. AT2R activation by C21 attenuated airway inflammation, oxidative damage and reduced airway remodeling. In addition, C21 abated airway destruction, ameliorated lung emphysema as well as improved lung functions in CS-exposed mice. C21 maintained lung RAS homeostasis by down-regulating Ang II level and modulating other components expression. C21 shifted CS-induced alveolar macrophages (AMs) M1 phenotype into M2 dominant phenotype. Besides, C21 reprogramed AM metabolism with less glycolysis and more mitochondrial respiration. C21 reduced expression of ACE protein level, whilst enhanced MAS receptor and AT2R expression in AMs from CS-exposed mice.