Effects of Risk Factors on In Situ Expression of Proinflammatory Markers Correlated to Carotid Plaque Instability

Appl Immunohistochem Mol Morphol. 2021 Nov-Dec;29(10):741-749. doi: 10.1097/PAI.0000000000000947.

Abstract

Background and aims: Several studies demonstrated a role of active chronic inflammatory infiltrate in carotid plaques progression suggesting a possible link between cardiovascular risk factors and inflammation-related plaque instability. The aim of this study is therefore to evaluate the possible effects of cardiovascular risk factors on in situ expression of proinflammatory markers associated with carotid plaque instability.

Methods and results: A tissue microarray containing carotid plaques from 36 symptomatic (major stroke or transient ischemic attack) and 37 asymptomatic patients was built. Serial sections were employed to evaluate the expression of some inflammatory markers by immunohistochemistry [CD3, CD4a, CD8, CD20, CD86, CD163, interleukin (IL)-2, IL-6, IL-17]. Immunohistochemical data were analyzed to study the possible associations between in situ expression of inflammatory biomarker and the main cardiovascular risk factors. Our data demonstrated that plaque instability is associated with the high in situ expression of some cytokines, such as IL-2, IL-6, IL-17. Besides the female sex, none of the risk factors analyzed showed a significant association between the in situ expression of these markers and unstable plaques. A significant increase of IL-6-positive and IL-17-positive cells was observed in unstable atheromatous plaques of female patients, as compared with unstable plaques of male patients.

Conclusions: Plaque destabilization is certainly correlated with the presence of the major cardiovascular risk factors, however, our results showed that, with the exception of sex, their action in the evolutive process of plaque instability seems rather nonspecific, favoring a general release of proinflammatory cytokines.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis*
  • Biomarkers / metabolism
  • Carotid Arteries* / metabolism
  • Carotid Arteries* / pathology
  • Carotid Artery Diseases* / metabolism
  • Carotid Artery Diseases* / pathology
  • Cytokines / biosynthesis*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic* / metabolism
  • Plaque, Atherosclerotic* / pathology
  • Risk Factors
  • Sex Factors

Substances

  • Antigens, CD
  • Biomarkers
  • Cytokines