title: Atg5 deficiency-mediated mitophagy aggravates cardiac inflammation and injury in response to angiotensin II.
abstract: OBJECTIVE
  Hypertension induces end-organ damage through inflammation, and autophagy plays a crucial role in the regulation of cellular homeostasis. In the present study, we aimed to define the role of autophagy in the development of inflammation and cardiac injury induced by angiotensin II (Ang II).
  
  
  RESULTS
  Autophagy protein 5 (Atg5) haplodeficiency (Atg5(+/-)) and age-matched wild-type (WT) C57BL/6J mice were infused with Ang II (1500 ng/kg/min) or saline for 7 days. Heart sections were stained with hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical stains. Cytokine and LC3 levels were measured using real-time PCR or western blot analysis. After Ang II infusion, the WT mice exhibited marked macrophage accumulation, cytokine expression, and reactive oxygen species (ROS) production compared with saline-infused controls. However, these effects induced by Ang II infusion were aggravated in Atg5(+/-) mice. These effects were associated with Atg5-mediated impaired autophagy, accompanied by increased production of ROS and activation of nuclear factor-κB (NF-κB) in macrophages. Finally, increased cardiac inflammation in Atg5 haplodeficient mice was associated with increased cardiac fibrosis.
  
  
  CONCLUSIONS
  Atg5 deficiency-mediated autophagy increases ROS production and NF-κB activity in macrophages, thereby contributing to cardiac inflammation and injury. Thus, improving autophagy may be a novel therapeutic strategy to ameliorate hypertension-induced inflammation and organ damage.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Jia
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Pathology, Capital Medial University, Beijing 100069, China. Electronic address: hhli1935@aliyun.com.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China. Electronic address: jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000071187:Autophagy-Related Protein 5; D006335:Heart Injuries / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D063306:Mitophagy; D017382:Reactive Oxygen Species / Q000633:toxicity
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D000804:Angiotensin II
keywords: Autophagy protein 5; Inflammation; Macrophage; Mitophagy