title: Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice.
abstract: Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE(-/-) mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.|e Institute of Medical Science, University of Toronto, Ontario, Canada.
authors.forename: Azza
authors.initials: A
authors.lastname: Ramadan
authors.affiliation: b Division of Vascular & Endovascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.|f Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wheatcroft
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Quan
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.|b Division of Vascular & Endovascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.|f Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Fina
authors.initials: F
authors.lastname: Lovren
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Dhingra
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.|c Division of Endocrinology & Metabolism, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Hwee
authors.initials: H
authors.lastname: Teoh
authors.affiliation: b Division of Vascular & Endovascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.|f Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Omran
authors.affiliation: d Division of Cardiology, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.|e Institute of Medical Science, University of Toronto, Ontario, Canada.|g Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.affiliation: a Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.|e Institute of Medical Science, University of Toronto, Ontario, Canada.|f Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001343:Autophagy / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II; D002738:Chloroquine; D003094:Collagen; D004549:Elastin
keywords: abdominal aortic aneurysm; anévrisme aortique abdominal; autophagie; autophagy; chloroquine