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.

Modulation of Peripheral CD4+CD25+Foxp3+ Regulatory T Cells Ameliorates Surgical Stress-Induced Atherosclerotic Plaque Progression in ApoE-Deficient Mice

“…Annually, clinical manifestations of atherosclerosis, such as ischemic heart disease and stroke, account for 15 million deaths, globally (1). Although atherogenesis is generally regarded insidious in nature, numerous studies also describe more rapid, accelerated lesion progression triggered by physical and inflammatory stressors (2)(3)(4)(5). In line with these findings, we and others have demonstrated that systemic inflammation associated with major surgical interventions rapidly accelerates atherosclerotic plaque progression in a murine model of perioperative stress (6,7).…”

Global, regional, and national burdens of hypertensive heart disease from 1990 to 2019 ：A multilevel analysis based on the global burden of Disease Study 2019

“…Clinical practitioners can provide patients with medical advice on risks associated with cold exposure, such as maintaining warm housing and receiving flu vaccinations [ 46 ]. Previous mechanism studies have attempted to explore the relationship between environmental temperature and HHD, including systemic inflammation, the activation of the sympathetic nervous system, and heat shock proteins [ 47 , 48 ]. However, most of these are based on animal models, and the potential mechanisms in humans remain an area worthy of exploration [ 49 ].…”

Effects of Cold-inducible RNA-binding Protein (CIRP) on Liver Glycolysis during Acute Cold Exposure in C57BL/6 Mice

“…CIRP is associated with several signal transduction pathways required for cellular function, which are associated with both apoptosis and proliferation [46,47]. It has been reported that CIRP activates both the MAPK and NF-κB signaling pathways [48,49] and induces TRX expression [50]. In addition, CIRP overexpression was associated with reduced levels of p53, thereby downregulating proapoptotic genes and upregulating anti-apoptotic genes [51].…”