Proteomics

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Aortic smooth muscle cells in bicuspid valve patients


ABSTRACT: and with higher incidence if associated to bicuspid aortic valve (BAV) for unknown reasons. TAA is usually diagnosed fortuitously and the lack of effective drug therapy to delay progression and avoid dissection lies in the limited knowledge of pathophysiology. Objectives. We aimed to identify the molecular hallmarks that difference the aortic dilatation associated to bicuspid (BAV) and tricuspid aortic valve (TAV) patients while setting plasma diagnostic molecular panels valve-associated. Methods. Sporadic TAA patients and control subjects (n=91) were classified according to valve type (BAV, TAV). Vascular smooth muscle cells isolated from TAA patients’ aortas were firstly analyzed by mass spectrometry based high-throughput proteomics according to valve type. Extracellularly secreted proteins were secondly analyzed in plasma from TAA patients versus control subjects as diagnostic candidates. Results. Aneurysmal aortas from BAV patients showed a stress phenotype, weakened extracellular matrix interactions, DNA damage and affected protein homeostasis compared to TAV patients. Two plasma marker panels of sporadic TAA valveassociated were identified, showing significant correlation with aortic diameter for C1QTNF5, LAMA2, and SPARC proteins, in BAV patients, and for CP and FAP proteins, in TAV patients. Conclusions. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA while resembling aged arteries.The molecular pathways identified here support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Thoracic Aortic Aneurysm

SUBMITTER: Juan A Lopez  

LAB HEAD: Juan A Lopez

PROVIDER: PXD043062 | Pride | 2024-10-17

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
JAL_Glo_TMT_Dec2020_Fr1.msf Msf
JAL_Glo_TMT_Dec2020_Fr1.raw Raw
JAL_Glo_TMT_Dec2020_Fr2.msf Msf
JAL_Glo_TMT_Dec2020_Fr2.raw Raw
JAL_Glo_TMT_Dec2020_Fr3.msf Msf
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Publications

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.

Martin-Blazquez Ariadna A   Martin-Lorenzo Marta M   Santiago-Hernandez Aranzazu A   Heredero Angeles A   Donado Alicia A   Lopez Juan A JA   Anfaiha-Sanchez Miriam M   Ruiz-Jimenez Rocio R   Esteban Vanesa V   Vazquez Jesus J   Aldamiz-Echevarria Gonzalo G   Alvarez-Llamas Gloria G  

Journal of proteome research 20240409 8


Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by m  ...[more]

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