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.