Bioactive Lipids, Inflammation, and Coronary Artery Disease

• Applicant: Dr. Juliane Weikert
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390851560

The aim of this study is to investigate the relationship between the eicosanoid metabolism and atherosclerosis. Eicosanoids are bioactive lipids, which regulate the initiation, progression, and resolution of inflammatory processes. While eicosanoid of the arachidonic acid metabolism are mainly proinflammatoric, metabolites such as resolvins produced from omega-3 fatty acids regulate the resolution of inflammation. In the this study, plasma of n = 1000 patients without coronary stenosis, patients with a stenosis greater or equal 50% in all three coronary vessels, as well as patients with acute myocardial infarction will be investigated, so that a total of 3,000 patients will be included in the study. For this purpose plasma of patients of the LIFE Leipzig heart study will be used. The highly standardized sample collection has already been completed. The phenotyping of the patients includes a coronary angiography, carotis sonography and examination of the leg vessels as well as the acquisition of anthropometric data. Further, the data of the established markers of coronary artery disease and extensive genotyping are available. The method used for the quantification of eicosanoids and their precursors, the long-chain, polyunsaturated fatty acids (PUFAs), is liquid chromatography tandem mass spectrometry (LC-MS/MS). In Leipzig, we developed a method to quantify 94 eicosanoids as well as 7 PUFAs mainly of the proinflammatoric arachidonic acid metabolism. This method is currently being extended by the proresolute metabolites of omega-3 fatty acids such as resolvins. For the first time it is possible to determine the pro and anti-inflammatory and proresolute lipids, which act as agonists and antagonists in the inflammatory process, from a well characterized collective of patients.In this study, the following aims are to be achieved:1) Investigation of the relationship between PUFAs, eicosanoids, and coronary artery disease and other atherosclerotic vascular changes such as carotid plaques. Hence, diagnostic biomarkers will be determined.2) Determination of the prognostic value of the identified biomarkers with regard to stability of the atherosclerosis and other cardiovascular events. In addition, a SNP analysis is planned since only those patients will be included in the study, who were genotyped using Affymerix Axiom SNP array. Of particular interest are the enzymes involved in the biosynthesis of the PUFA metabolites (amongst others cyclooxygenase, lipoxygenase, and cytochrome P450-enzymes). Of these, some SNPs are already known leading to a misregulation of the enzymes, which can have a promoting and inhibiting effect for atherosclerosis.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Uta Ceglarek