Downregulation of miR-146a, cyclooxygenase-2 and advanced glycation end-products in simvastatin-treated older patients with hyperlipidemia.
OBJECTIVE
Hyperlipidemia is a disease with abnormally elevated levels of lipids/lipoproteins in the blood, and it is regarded as an important risk factor for cardiovascular and cerebrovascular diseases. Statins have been found to prevent vascular diseases by reducing low-density lipoprotein cholesterol and regulation of immune responses. Here, we aim to study the expression change of immune-related microRNA and genes in older patients with hyperlipidemia after treatment with simvastatin.


METHODS
A total of 25 older male patients with hyperlipidemia were included in the study and received simvastatin treatment (20 mg/day). Clinical characteristics of these patients were examined, including lipoprotein cholesterol, high-sensitivity C-reactive protein, blood routine and biochemical characters. We tested miR-146a, interleukin-1-receptor-associated kinase 1, tumor necrosis factor-receptor-associated factor 6 and cyclooxygenase-2 level by real-time polymerase chain reaction, and expressions of advanced glycation end-products, p53 and p21 were analyzed by enzyme-linked immunosorbent assay.


RESULTS
Simvastatin treatment effectively reduced total cholesterol and low-density lipoprotein cholesterol, but had little effect on high-density lipoprotein cholesterol. High-sensitivity C-reactive protein was slightly reduced. Expression of cyclooxygenase-2 and advanced glycation end-products were significantly reduced. Furthermore, simvastatin effectively reduced the expression of p53 and p21. Significantly downregulated miR-146a, and an obvious reduction of interleukin-1-receptor-associated kinase 1 were also detected, whereas tumor necrosis factor-receptor-associated factor 6 remained unchanged. Besides, there was a significant reduction of alanine transaminase, aspertate aminotransferase, alkaline phosphatase and lactate dehydrogenase.


CONCLUSIONS
Simvastatin treatment could inhibit inflammation and senescence-associated genes in older patients with hyperlipidemia, suggesting its application in inflammatory and age-related diseases.
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Zhou Xin
ZX
Yang
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Ya Zhen
YZ
Wang
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Bing Bing
BB
Jia
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Gen Xiang
GX
Mao
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Yuan Dong
YD
Lv
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.
Guo Fu
GF
Wang
Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.|Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Hong
H
Yu
D000368:Aged; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019821:Simvastatin / Q000627:therapeutic use*
D017127:Glycation End Products, Advanced; D000960:Hypolipidemic Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D019821:Simvastatin; D051546:Cyclooxygenase 2
advanced glycation end-products; cyclooxygenase-2; hyperlipidemia; miR-146a; simvastatin