The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery

Cardiovasc Pathol. 2014 Jul-Aug;23(4):217-23. doi: 10.1016/j.carpath.2014.03.009. Epub 2014 Apr 5.


Background: Previous studies have reported important roles of endothelin-1 (ET-1) and angiotensin II (Ang II) in the pathogenesis of atherosclerosis. However, the expression of these two proteins and the underlying mechanisms in human atherosclerotic coronary arteries are largely unknown.

Methods: We examined the expression of ET-1 and Ang II in pericardial fluid and coronary arteries from 25 individuals (n = 25) using enzyme-linked immuno sorbent assay (ELISA) and immunohistochemistry. Twelve patients died from acute coronary syndrome were classified as atherosclerotic plaque group (AP group) (n = 12), while 13 patients died from other causes were classified as non-AP group (n = 13). Meanwhile, we performed reverse transcription-polymerase chain reaction (RT-PCR) to measure the expression of six microRNAs targeting ET-1 in formalin-fixed, paraffin-embedded coronary arteries.

Results: Our data showed that ET-1 was significantly higher in both pericardial fluid and coronary arteries from AP group. However, Ang II showed no significant difference in pericardial fluid between the two groups, while it was even significantly lower in coronary arteries from AP group. Besides, miR-125a-5p, miR-155, and miR-199a/b-3p, which suppressed the expression of ET-1, were down-regulated in the coronary arteries from AP group.

Conclusion: The up-regulation of ET-1, regulated by miR-125a-5p, miR-155, and miR-199a/b-3p, indicated that ET-1 played an important role in human coronary atherosclerosis.

Summary: We focused on the human coronary arteries with atherosclerotic plaques. The expression of ET-1, as well as its upstream miRNAs, was determined. Unlike any of previous study regarding miRNAs expression, we could exclude the discrepancy of artery-bed-specific miRNA expression. Besides, our data indicated, to some degree, that ET-1 might play a more vital role than Ang II in coronary atherosclerosis.

Keywords: Angiotensin II; Coronary atherosclerosis; Endothelin-1; MicroRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / metabolism
  • Acute Coronary Syndrome / pathology
  • Adult
  • Angiotensin II / metabolism
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / pathology
  • Down-Regulation
  • Endothelin-1 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pericardial Effusion / metabolism
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation


  • Endothelin-1
  • MIRN125 microRNA, human
  • MIRN155 microRNA, human
  • MicroRNAs
  • mirn199 microRNA, human
  • Angiotensin II