Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin.
OBJECTIVE
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.
Chen
Yang Xin
YX
Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120 China.
Wang
Xiao Qiao
XQ
Fu
Yun
Y
Yao
You Jie
YJ
Kong
Min Yi
MY
Nie
Ru Qiong
RQ
Wang
Jing Feng
JF
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000276:immunology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology*
D000924:Anticholesteremic Agents; D015415:Biomarkers; D001786:Blood Glucose; D004041:Dietary Fats; D006538:Heptanoic Acids; D007328:Insulin; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin