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


Journal

Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796

Informations de publication

Date de publication:
Historique:
received: 09 10 2020
accepted: 13 04 2021
pubmed: 28 5 2021
medline: 8 3 2022
entrez: 27 5 2021
Statut: ppublish

Résumé

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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 34039839
doi: 10.1097/PAI.0000000000000947
pii: 00129039-202111000-00005
doi:

Substances chimiques

Antigens, CD 0
Biomarkers 0
Cytokines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

741-749

Informations de copyright

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

Références

Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204–212.
Hansson GK, Libby P, Tabas I. Inflammation and plaque vulnerability. J Intern Med. 2015;278:483–493.
Spagnoli LG, Bonanno E, Sangiorgi G, et al. Role of inflammation in atherosclerosis. J Nucl Med. 2007;48:1800–1815.
Taleb S. Inflammation in atherosclerosis. Arch Cardiovasc Dis. 2016;109:708–715.
Zhu Y, Xian X, Wang Z, et al. Research progress on the relationship between atherosclerosis and inflammation. Biomolecules. 2018;8:80.
Van Bruggen N, Ouyang W. Th17 cells at the crossroads of autoimmunity, inflammation, and atherosclerosis. Immunity. 2014;40:10–12.
Moghaddam AS, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization and function in health and disease. J Cell Physiol. 2018;233:6425–6440.
De Paoli F, Staels B, Chinetti-Gbaguidi G. Macrophage phenotypes and their modulation in atherosclerosis. Circ J. 2014;78:1775–1781.
Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34:719–728.
Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262–1275.
Spagnoli LG, Mauriello A, Sangiorgi G, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA. 2004;292:1845–1852.
Kinlay S, Egido J. Inflammatory biomarkers in stable atherosclerosis. Am J Cardiol. 2006;98:2P–8P.
Koenig W, Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol. 2007;27:15–26.
Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14–20.
Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization. Front Biosci. 2008;13:453–461.
Porcheray F, Viaud S, Rimaniol AC, et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol. 2005;142:481–489.
Lee S, Huen S, Nishio H, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22:317–326.
Feig JE, Rong JX, Shamir R, et al. HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc Natl Acad Sci USA. 2011;108:7166–7171.
Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity. 2017;47:621–634.
Nikiforov NG, Kornienko VY, Karagodin VP, et al. Macrophage activation in atherosclerosis. Message 1: activation of macrophages normally and in atherosclerotic lesions. Patol Fiziol Eksp Ter. 2015;3:128–131.
Legein B, Temmerman L, Biessen EAL, et al. Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci. 2013;70:3847–3869.
Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006;86:515–581.
Lavin Y, Winter D, Blecher-Gonen R, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014;159:1312–1326.
Scimeca M, Anemona L, Granaglia A, et al. Plaque calcification is driven by different mechanisms of mineralization associated with specific cardiovascular risk ractors. Nutr Metab Cardiovasc Dis. 2019;29:1330–1336.
Cardellini M, Rovella V, Scimeca M, et al. Chronic kidney disease is linked to carotid nodular calcification, an unstable plaque not correlated to inflammation. Aging Dis. 2019;10:71–81.
Mauriello A, Sangiorgi GM, Virmani R, et al. A pathobiologic link between risk factors profile and morphological markers of carotid instability. Atherosclerosis. 2010;208:572–580.
Mauriello A, Servadei F, Sangiorgi G, et al. Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion. Atherosclerosis. 2011;218:356–362.
Francula-Zaninovic S, Nola IA. Management of measurable variable cardiovascular disease' risk factors. Curr Cardiol Rev. 2018;14:153–163.
Libby P, Loscalzo J, Ridker PM, et al. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week. J Am Coll Cardiol. 2018;72:2071–2081.
Herrington W, Lacey B, Sherliker P, et al. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res. 2016;118:535–546.
Negi S, Anand A. Atherosclerotic coronary heart disease-epidemiology, classification and management. Cardiovasc Hematol Disord Drug Targets. 2010;10:257–261.
Scimeca M, Giannini E, Antonacci C, et al. Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics. BMC Cancer. 2014;14:286.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:2199–2269.
Bairaktari ET, Seferiadis KI, Elisaf MS. Evaluation of methods for the measurement of low-density lipoprotein cholesterol. J Cardiovasc Pharmacol Ther. 2005;10:45–54.
Glaudemans AWJM, Bonanno E, Galli F, et al. In vivo and in vitro evidence that 99mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery. Eur J Nucl Med Mol Imaging. 2014;41:1710–1719.
Elkind MS, Rundek T, Sciacca RR, et al. Interleukin-2 levels are associated with carotid artery intima-media thickness. Atherosclerosis. 2005;180:181–187.
Taleb S, Tedgui A. IL-17 in atherosclerosis: the good and the bad. Cardiovasc Res. 2018;114:7–9.
Allama G, Abdel-Moneimc A, Gaber AM. The pleiotropic role of interleukin-17 in atherosclerosis. Biomed Pharmacother. 2018;106:1412–1418.
Erbel C, Dengler TJ, Wangler S, et al. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Res Cardiol. 2011;106:125–134.
Nosalski R, Guzik TJ. Perivascular adipose tissue inflammation in vascular disease. Br J Pharmacol. 2017;174:3496–3513.
Magenta A, Sileno S, D’Agostino M, et al. Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker. Clin Sci (Lond). 2018;132:2423–2436.
Eltoft A, Arntzen KA, Wilsgaard T, et al. Interleukin-6 is an independent predictor of progressive atherosclerosis in the carotid artery: the Tromsø Study. Atherosclerosis. 2018;271:1–8.
Sangiorgi G, Roversi S, Biondi Zoccai G, et al. Sex-related differences in carotid plaque features and inflammation. J Vasc Surg. 2013;57:338–344.
Villablanca AC, Jayachandran M, Banka C. Atherosclerosis and sex hormones: current concepts. Clin Sci (Lond). 2010;119:493–513.
Gilliver SC. Sex steroids as inflammatory regulators. J Steroid Biochem Mol Biol. 2010;120:105–115.
Fairweather D. Sex differences in inflammation during atherosclerosis. Clin Med Insights Cardiol. 2015;8(suppl 3):49–59.
Yahagi K, Davis HR, Arbustini E, et al. Sex differences in coronary artery disease: pathological observations. Atherosclerosis. 2015;239:260–267.
Eligini S, Cosentino N, Fiorelli S, et al. Biological profile of monocyte-derived macrophages in coronary heart disease patients: implications for plaque morphology. Sci Rep. 2019;9:8680.
Spitz C, Winkels H, Bürger C, et al. Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential. Cell Mol Life Sci. 2016;73:901–922.
Tabas I, Bornfeldt KE. Macrophage phenotype and function in different stages of atherosclerosis. Circ Res. 2016;118:653–667.
Tajbakhsh A, Rezaee M, Kovanen PT, et al. Efferocytosis in atherosclerotic lesions: malfunctioning regulatory pathways and control mechanisms. Pharmacol Ther. 2018;188:12–25.

Auteurs

Manuela Montanaro (M)

Departments of Experimental Medicine.

Manuel Scimeca (M)

Departments of Experimental Medicine.
University of San Raffaele.
Saint Camillus International University of Health Sciences, Rome, Italy.

Nicola Toschi (N)

Biomedicine and Prevention, University of Rome "Tor Vergata".
Imaging Martinos Center for Biomedical Imaging.
Harvard Medical School, Massachusetts General Hospital, Boston, MA.

Elena Bonanno (E)

Departments of Experimental Medicine.

Erica Giacobbi (E)

Departments of Experimental Medicine.

Francesca Servadei (F)

Departments of Experimental Medicine.

Arnaldo Ippoliti (A)

Biomedicine and Prevention, University of Rome "Tor Vergata".

Giuseppe Santeusanio (G)

Departments of Experimental Medicine.

Alessandro Mauriello (A)

Departments of Experimental Medicine.

Lucia Anemona (L)

Departments of Experimental Medicine.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH