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Influence of perivascular brown adipose tissue on calcified aortic valve disease

The focus of this proposal lies on the interplay between perivascular adipose tissue (PVAT) and aortic stenosis. The project combines the expertise of our laboratory in the field of adipose tissue and metabolism with our long-standing know-how in vascular physiology and regulation of vessel tone. Two major types of adipose tissue can be distinguished: white adipose tissue (WAT) which stores energy and brown adipose tissue (BAT) which dissipates energy. In addition, intermediate types/colors of fat exist and “browning” of WAT as well as “whitening” of BAT have been described. PVAT depots can be found in the immediate proximity of the aortic wall and valve. PVAT has the phenotypic characteristics of brown fat, including the capacity to dissipate energy. All adipose tissues are known to function as endocrine organs, secreting paracrine factors that regulate both the tissue itself and surrounding organs. Given the close proximity of PVAT and the aortic wall as well as the aortic valve, we hypothesize that PVAT plays a major role in aortic disease (AD) such as aortic stenosis (AS) or aortic aneurysm (AA). In the first funding period, the following aims will be studied: In Aim 1, we study how PVAT signals correlate with aortic valve disease in AS patients. Moreover, we will identify factors secreted by PVAT that could have an impact in AS. In Aim 2, we will study functional relevance of intercellular signaling between PVAT and valve cells in vitro. In Aim 3, we will analyze the influence of PVAT signals identified in Aim 1 and 2 on AS in mouse models in vivo. Finally, in Aim 4, we will focus on the role of PVAT in AA.



A08 Hypothesis: Activation of brown-like perivascular adipocytes leads to the release of anti-inflammatory and anti-calcific cytokines and paracrine factors, influencing the development of AS.

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