Obesity is a major risk factor for cardiovascular diseases (CVD), the leading cause of global mortality. Endothelial dysfunction, a feature of obesity, has been identified as an early driver for CVD development. Low-grade, chronic inflammation due to obesity-induced subintimal lipid deposition plays an important role in the onset of obesity-associated CVD. Particularly macrophages accumulate in dysfunctional adipose tissue and vessels of obese patients and exert proinflammatory actions through e.g. release of cytokines. Yet, the interplay between macrophages, adipocytes, and endothelial dysfunction in CVD development is not well understood. We recently identified ectopic olfactory receptor 2 (Olfr2) expression in vascular and adipose tissue macrophages (ATM), which was increased in obese mice. Of note, genetic deficiency for Olfr2 reduced atherosclerosis and macrophage inflammation. The aim of this project is to uncover the role of Olfr2 in ATM-mediated inflammation in the context of obesity-induced endothelial dysfunction. We will address if Olfr2 affects adipose tissue inflammation and metabolism. Furthermore, we will assess vascular dysfunction in obese Olfr2-deficient and control mice by sonography and organ bath investigations.
Obesity greatly impacts overall health and can lead to the development of chronic diseases including CVD. Inflammation is a key mechanism rewiring adipose tissue, metabolic and vascular function. Yet, no clinical therapies targeting inflammation in obesity are available and novel pathways that curb adipose tissue inflammation while preserving host immunity are needed.
In collaboration with Prof. Marco Orecchioni at Augusta University, we will address in this project:
Clinic III of Internal Medicine - Experimental Cardiology
CMMC - PI - B 12
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Clinic III of Internal Medicine - Experimental Cardiology
Kerpener Str. 62
50937 Cologne
Clinic III of Internal Medicine
CMMC - Co-PI - B 12
martin.mollenhauer[at]uk-koeln.de
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+49 221 478 87372
Clinic III of Internal Medicine
Kerpener Str. 62
50937 Cologne
https://kardiologie.uk-koeln.de/forschung/inflammation-im-rahmen-der-herzinsuffizienz/
PostDoc: Dr. rer. nat. Felix Picard
PhD students: Elena Wagner, Lauren De Vore
Master student: Yein Park (start summer 23)
Medical student: Patrik Schelemei
Technician: Katharina Tinaz