title: Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E‑deficient mice.
abstract: The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold‑induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week‑old, apolipoprotein E (ApoE)‑deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4˚C for 4 h per day, while the mice in the control group were kept in a room at 24˚C. Cold‑exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low‑density lipoprotein and high‑density lipoprotein. The hematoxylin and eosin‑stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (P<0.01). Furthermore, cold‑treated mice exhibited significantly decreased plaque collagen and vascular smooth muscle cell deposition and increased macrophage and lymphocyte content (P<0.05 or P<0.01), which are typical features of atherosclerotic plaque instability. Additionally, the protein expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and MMP‑14 were significantly increased (P<0.05 or P<0.01), whereas tissue inhibitor of matrix metalloproteinase (TIMP)‑1 expression was decreased (P<0.05) following exposure to a cold environment. The present study demonstrated that chronic intermittent cold stress may increase atherosclerotic plaque size and promote plaque instability in ApoE‑deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Xiuchuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003080:Cold Temperature; D003094:Collagen / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D019715:Tissue Inhibitor of Metalloproteinase-1; D014280:Triglycerides; D003094:Collagen; D002784:Cholesterol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14