Downregulation of miR-146a, cyclooxygenase-2 and advanced glycation end-products in simvastatin-treated older patients with hyperlipidemia

作者：Yang, Zhou Xin; Wang, Ya Zhen; Jia, Bing Bing; Mao, Gen Xiang; Lv, Yuan Dong; Wang, Guo Fu^*; Yu, Hong^*

来源：Geriatrics and Gerontology International, 2016, 16(3): 322-328.

DOI：10.1111/ggi.12472

• advanced glycation end-products
• cyclooxygenase-2
• hyperlipidemia
• miR-146a
• simvastatin

AimHyperlipidemia 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. @@@ MethodsA total of 25 older male patients with hyperlipidemia were included in the study and received simvastatin treatment (20mg/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 kinase1, tumor necrosis factor-receptor-associated factor6 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. @@@ ResultsSimvastatin 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 kinase1were also detected, whereas tumor necrosis factor-receptor-associated factor6 remained unchanged. Besides, there was a significant reduction of alanine transaminase, aspertate aminotransferase, alkaline phosphatase and lactate dehydrogenase. @@@ ConclusionSimvastatin treatment could inhibit inflammation and senescence-associated genes in older patients with hyperlipidemia, suggesting its application in inflammatory and age-related diseases. Geriatr Gerontol Int 2015; ..: ..-...

• 出版日期2016-3
• 单位浙江大学; 浙江医院