Project details

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The role of inflammatory markers in the development of myocardial injury

Keywords:
cardiology inflammation biomarkers

Researchers:
Prof. dr. P. van der Harst

Nature of the research:
Gain insights into the role of inflammatory markers in the development of myocardial injury

Fields of study:
cardiology

Background / introduction
Coronary heart disease (CHD) is still associated with high morbidity and mortality numbers, despite successful prevention strategies such as effective antihypertensive and lipid-lowering drugs. It is known that inflammation is an important factor throughout the development of CHD, from endothelial dysfunction to onset of atherosclerotic plaque rupture(1,2). Currently, the growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms.
Two biomarkers, which have been recently described to be involved in the inflammatory process are chemokine CcL7 (Ccl7) and B-cell activating factor (Baff). Recently, research has shown that after acute myocardial infarction in mice, mature B lymphocytes were activated to produce Ccl7 (3). This chemokine induces monocyte mobilization from the bone marrow, leading to enhanced myocardial inflammation, tissue injury and deterioration of myocardial function. In addition, deficiency of B-cell stimulating factor signalling, which is required for the maintenance of mature B2 cells, is associated with lower concentrations of circulating Ccl7 and decreased monocyte mobilization.
However, less is known about the levels of Ccl7 and Baff over time in patients with ST-evelation myocardial infarction (STEMI). No previous studies have sought to study the association of Ccl7 and Baff and myocardial damage in humans. To gain insights into the potential role of Ccl7 and Baff we plan to determine Ccl7 and Baff levels in the GIPS III cohort, which consists of 379 STEMI patients.
Research question / problem definition
1. What is the role of Ccl7 and Baff on the long term in patients with myocardial infarction?

2. Is there a difference in Ccl7 and Baff levels between patients with normal and reduced reperfusion?

3. Are Ccl7 and Baff levels correlated with infarct size at 4 months?
Workplan
Ccl7 and Baff levels will be measured in the GIPS III cohort using Enzyme-Linked Immuno Sorbent Assay (ELISA). We will develop these ELISAs ourselves. Ccl7 and Baff levels will be measured at six time points, and will be correlated to other laboratory biomarkers of inflammation and cardiovascular disease from the GIPS III database.
References
(1) Boekholdt SM, Stroes ES. The interleukin-6 pathway and atherosclerosis. Lancet 2012 Mar 31;379(9822):1176-1178.
(2) Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 2011 Nov 7;17(11):1410-1422.
(3) Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guerin C, et al. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med 2013 Oct;19(10):1273-1280.
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