Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin.

AIMS: To evaluate the role of inflammation in vascular endothelial function of hyperlipidemic rabbits and atorvastatin's effects on it. METHODS: 22 rabbits were divided into high-fat diet and atorvastatin plus high-fat diet group. Basic levels of total and low-density lipoprotein cholesterol, triglyceride, C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), fasting blood glucose (FBG), insulin and endothelial function were measured when grouping. Eight weeks later, all above parameters were remeasured and repeated again at days 1, 4 and 7 after atorvastatin withdrawal. RESULTS: Eight-week high-fat diet could not cause the changes of FBG and insulin, but significantly induce increased blood lipids as well as inflammatory markers, imbalance between ET-1 and NO, and direct endothelial dysfunction, which could be significantly improved by atorvastatin therapy but could not be well controlled to near baseline. Abrupt withdrawal of atorvastatin caused sharp increase of inflammatory markers and endothelial dysfunction at days 4 and 7 after atorvastatin withdrawal independent of the changes of blood lipids. CONCLUSIONS: High-fat diet could cause endothelial dysfunction associated with inflammation, and atorvastatin could counter-regulate it. Sudden withdrawal of statins could induce rebound of inflammatory response and endothelial dysfunction independent of changes of lipids, which may be responsible for increased cardiovascular events in patients with coronary artery disease after withdrawing statins.

[PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes].

OBJECTIVE: To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes. METHODS: Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis. RESULTS: Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V. CONCLUSION: Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.