Intermittent Hypobaric Hypoxia Promotes Atherosclerotic Plaque Instability in ApoE-Deficient Mice

Abstract

. Intermittent hypobaric hypoxia promotes atherosclerotic plaque instability in ApoE-deficient mice. High Alt Med Biol 14:175-180, 2013.-Aim: Sudden cardiac death is one of the most frequent causes of death at high altitude. It has been reported that the intermittent normobaric hypoxia experienced by patients with obstructive sleep apnea may enhance the development of atherosclerosis. However, the effect of hypobaric hypoxia, which mimics the ambient air at high altitude, in the development of atherosclerosis has not been investigated. Methods: Twenty male ApoE-deficient mice, 8 weeks of age, were subjected to either control conditions or intermittent hypobaric hypoxia (IHH) for 8 weeks. Mice in the IHH group were exposed to a hypobaric chamber that replicated the hypobaric hypoxia conditions found at 4000 m altitude for 8 hours a day. Results: IHH-exposed mice did not significantly differ from control mice in plasma lipid levels, including triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein. The hematoxylin and eosinstained sections of the aortic root showed similar plaque size between the groups. However, IHH-treated mice exhibited significantly decreased plaque collagen content, a feature of atherosclerotic plaque stability. Additionally, matrix metalloproteinase (MMP)-9 protein expression was significantly increased, whereas tissue inhibitor of MMP (TIMP)-2 expression was decreased after exposure to IHH. Conclusion: IHH may promote atherosclerotic plaque instability in ApoE-deficient mice by changing the balance of MMPs and TIMPs.

Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E-deficient mice

“…Fasting blood samples were obtained at the end of the experiments. Glucose, triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured by colorimetric assays using commercially available kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, Jiangsu, China) in accordance with the manufacturer's instructions (13).…”

Hypoxemia as a model for high altitude and cardiovascular risk reduction

“…Nonetheless, intermittent hypobaric hypoxia (IHH) has been investigated in the venerable apoE -/-mice. Jiang et al [15] exposed apoE -/-mice to either control conditions or IHH for 8 weeks. Mice in the IHH group were exposed to a hypobaric chamber that replicated the hypobaric hypoxia conditions found at 4000 m altitude for Fig.…”

Suxiaojiuxin Pill Enhances Atherosclerotic Plaque Stability by Modulating the MMPs/TIMPs Balance in ApoE-deficient Mice

“…The balance between MMPs and TIMPs has an important role in the regulation of the normal metabolism of vascular ECM. 13,49 Imbalance between MMPs and TIMPs may lead to fibrous cap thinner and contribute to plaque instability. 50 To investigate the effect of SX on the balance MMPs/TIMPs in ApoEdeficient mice atherosclerotic plaques, the effect of SX on MMP-2, MMP-9, TIMP-1, and TIMP-2 was evaluated by WB.…”

“…Hence, this model has been widely used to evaluate the atherosclerotic plaque stability. [11][12][13] Suxiaojiuxin pill (SX) is composed of Rhizoma and Borneolum and used for the treatment of coronary heart disease and angina pectoris. 14,15 It is widely used as the clinical emergency medicine with no obvious discomfort, side effects, and drug resistance.…”