Rekrutierung von Immunzellen in das perivaskuläre Fettgewebe bei Adipositas – Bedeutung von Leptin

Recruitment of immune cells into perivascular adipose tissue in obesity - Effect of leptin

by Sebastian Herzberg
Doctoral thesis
Date of Examination:2018-06-14
Date of issue:2018-06-06
Advisor:Prof. Dr. Katrin Schäfer
Referee:Prof. Dr. Katrin Schäfer
Referee:Prof. Dr. Jörg Wilting
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-6900

 

 

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Abstract

English

Obesity is a well-known risk factor for the development of atherosclerosis and cardiovascular diseases and is associated with hyperleptinemia and a proinflammatory state. Besides the effect of visceral adipose tissue, newer clinical and experimental studies point to a greater impact of perivascular adipose tissue inflammation on severity of cardiovascular diseases and atherosclerotic lesions. A critical point in the development of adipose tissue inflammation is the recruitment of immune cells into the vessel wall by an integrin mediated adhesion to the endothelial cells. In obesity hyperleptinemia leads to increased activation of endothelial cells and upregulates the expression of VCAM-1, the adhesion molecule for Integrin 𝛼4𝛽1. The aim of this thesis was to examine a leptin-dependent recruitment of Integrin 𝛼4𝛽1 positive immune cells into the vessel wall.  For this purpose, at first C57Bl/6 mice were set on high fat diet for 8 weeks to induce obesity. Then visceral as well as perivascular adipose tissue was analyzed for specific immune cell subpopulations using histochemical, molecularbiological and flow cytometrical methods and compared to normal weight controls. To determine the leptin-dependence of these mechanisms also leptin-deficient ob/ob mice were analyzed. As a second step, human peri- and epicardiac adipose tissue samples from patients undergoing cardiac surgery were analyzed pursuant to the murine model for their level of specific immune cells using flow cytometry. Objective of this study was to figure out a leptin-dependent relation between perivascular adipose tissue inflammation and severity of coronary artery disease.
Keywords: Leptin; VCAM-1; obesity; atherosclerosis; CAD; perivascular adipose tissue; inflammation; adipokines; integrin a4b1
 
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