title: Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice.
abstract: Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology.
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Cong-Lin
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA; Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA; Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Cleverson
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA; Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Chongzhe
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif, USA.
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Levy
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Mass, USA; Department of Cardiovascular, The Second Hospital Affiliated to Guangzhou Medical University, Guangzhou Institute of Cardiovascular Disease, Guangzhou 510182, Guangdong Province, China. Electronic address: gongxiong.wu@joslin.harvard.edu.
authors.forename: Gongxiong
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA. Electronic address: gshi@bwh.harvard.edu.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D018450:Disease Progression; D005938:Glucocorticoids / Q000494:pharmacology; D006967:Hypersensitivity / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000150:complications* / Q000188:drug therapy / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D005938:Glucocorticoids; D019819:Budesonide; D010047:Ovalbumin; D007665:Ketotifen