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

Geriatr Gerontol Int. 2016 Mar;16(3):322-8. doi: 10.1111/ggi.12472. Epub 2015 Feb 27.

Abstract

Aim: 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.

Conclusion: Simvastatin treatment could inhibit inflammation and senescence-associated genes in older patients with hyperlipidemia, suggesting its application in inflammatory and age-related diseases.

Keywords: advanced glycation end-products; cyclooxygenase-2; hyperlipidemia; miR-146a; simvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / physiology*
  • Down-Regulation*
  • Gene Expression Regulation
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / physiology*
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics*
  • Hypolipidemic Agents / therapeutic use*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Simvastatin / therapeutic use*

Substances

  • Glycation End Products, Advanced
  • Hypolipidemic Agents
  • MIRN146 microRNA, human
  • MicroRNAs
  • Simvastatin
  • Cyclooxygenase 2