Correlations between gene expression highlight a different activation of ACE/TLR4/PTGS2 signaling in symptomatic and asymptomatic plaques in atherosclerotic patients

Mol Biol Rep. 2018 Aug;45(4):657-662. doi: 10.1007/s11033-018-4207-7. Epub 2018 Jun 19.

Abstract

Inflammation has a key role and translates the effects of many known risk factors for the disease in atherosclerotic vulnerable plaques. Aiming to look into the elements that induce the development of either a vulnerable or stable atherosclerotic plaque, and considering that inflammation has a central role in the progression of lesions, we analyzed the expression of genes involved in the ACE/TLR4/PTGS2 signaling in carotid plaques of symptomatic and asymptomatic patients. Patients with internal carotid artery stenosis undergoing carotid endarterectomy at Verona University Hospital were included in this study. A total of 71 patients was considered for gene expression analysis (29 atherothrombotic stroke patients and 42 asymptomatic patients). Total RNA was extracted from the excised plaques and expression of PTGS2, ACE, TLR4, PTGER4, PTGER3, EPRAP and ACSL4 genes was analyzed by real-time PCR. The correlation between the pair of genes was studied by Spearman coefficient. From the analyzed genes, we did not observe any individual difference in gene expression but the network of co-expressed genes suggests a different activation of pathways in the two groups of plaques.

Keywords: Atherosclerosis; Gene correlations; Gene expression; Plaque instability.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Carotid Arteries
  • Carotid Stenosis / genetics
  • Coenzyme A Ligases
  • Cyclooxygenase 2 / genetics
  • Female
  • Gene Expression
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / metabolism
  • Receptors, Prostaglandin E, EP3 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Risk Factors
  • Signal Transduction / genetics
  • Toll-Like Receptor 4 / genetics
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology

Substances

  • PTGER3 protein, human
  • PTGER4 protein, human
  • Receptors, Prostaglandin E, EP3 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Coenzyme A Ligases
  • long-chain-fatty-acid-CoA ligase