In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. Suppl_1 ( 2019-08-02)
Abstract:
Heart Failure (HF) is a complex clinical syndrome defined by the heart’s inability to adequately perfuse the human body. The clinical progression of HF has been linked to the pathological activation of CF, which contributes to adverse remodeling and cardiac fibrosis. Previous studies have shown that unloading the failing heart via mechanical circulatory support devices contributes to reverse remodeling, improving both cardiac structure and function. However, despite the importance of CF in biology and disease, little is known regarding CF-specific mechanisms and functions during cardiac remodeling and reverse remodeling. Moreover, most human studies have relied on in vitro culture systems to investigate CF function, despite the fact that extended culturing leads to phenotypic changes in CF. Here, we apply state-of-the-art mass spectrometry approaches to discover and quantify cell surface and extracellular matrix (ECM) proteins to 1) develop an optimized CF culture system that allows for the preservation of their in situ phenotype and 2) study CF isolated from failing hearts, including failing hearts treated with mechanical circulatory support to identify novel targets for tracking and studying disease. To date, we have identified 〉 600 surface N- glycoproteins on primary human CF (n=12), including those with known relevance to CF ( e.g. BGN, BSG, FBN1) and those not previously described within CF ( e.g. HHIP, NFACS, GPNMB). In CF samples that were passaged ex vivo , cell surface and ECM N- glycoproteins that are associated with a phenotype switch ( e.g. COL5A1, ECM1, FBLN5, LAMB2) were detected and changes in their abundance correlated with increased expression of α-SMA. Our studies also identified cell surface and ECM proteins that have not been previously associated with the heart and those with known relevance to HF, cardiac remodeling and fibrosis ( e.g. BGN, GLUT8, ITGA11). Current efforts are underway to quantify surface proteins of interest to determine how their abundance changes during reverse remodeling in the context of HF. Overall, this work allowed for the development of an optimized CF culture system and revealed new cell-type specific molecular targets to study and track reverse remodeling in the context of advanced HF.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.125.suppl_1.246
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
1467838-X
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