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Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes


Wyss, C A; Neidhart, M; Altwegg, L; Spanaus, K S; Yonekawa, K; Wischnewsky, M B; Corti, R; Kucher, N; Roffi, M; Eberli, F R; Amann-Vesti, B; Gay, S; von Eckardstein, Arnold; Lüscher, T F; Maier, W (2010). Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes. European Heart Journal, 31(12):1457-1469.

Abstract

AIMS: Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients. METHODS AND RESULTS: In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1alpha, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-alpha, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05). CONCLUSION: In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in ACS.

AIMS: Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients. METHODS AND RESULTS: In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1alpha, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-alpha, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05). CONCLUSION: In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in ACS.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Angiology
04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
540 Chemistry
Language:English
Date:2010
Deposited On:17 Aug 2010 15:17
Last Modified:05 Apr 2016 14:12
Publisher:Oxford University Press
ISSN:0195-668X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1093/eurheartj/ehq084
PubMed ID:20447947
Permanent URL: http://doi.org/10.5167/uzh-35114

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