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Published on: October 20, 2023
Proteomic profile of human aortic stenosis: insights into the degenerative process
Tatiana Martín-Rojas1, Felix Gil-Dones, Luis F Lopez-Almodovar
1Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Insights
Degenerative aortic stenosis involves significant protein changes in heart valves, unlike coronary artery disease. Understanding these protein alterations is crucial for developing new preventive strategies for aortic stenosis.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Pathophysiology
Background:
- Degenerative aortic stenosis is a leading cause of heart valve replacement worldwide.
- Unlike coronary artery disease, it is not effectively managed by modifying traditional risk factors.
- Understanding the underlying pathophysiology is essential for developing preventive strategies.
Purpose of the Study:
- To investigate the proteomic differences between stenotic aortic valves and normal control valves.
- To identify key proteins involved in the pathogenesis of degenerative aortic stenosis.
Main Methods:
- Proteomic analysis of aortic valve tissue from patients with degenerative aortic stenosis and healthy controls.
- Quantitative differential electrophoresis (2D-DIGE) and mass spectrometry were employed.
- Samples were obtained from 20 patients undergoing valve replacement and 20 normal control valves from necropsies.
Main Results:
- 35 protein species were significantly increased in stenotic aortic valves, including apolipoprotein AI, alpha-1-antitrypsin, and serum albumin.
- 8 protein species were decreased, such as transgelin, haptoglobin, and glutathione peroxidase 3.
- Identified proteins are involved in critical cardiovascular processes like fibrosis, homeostasis, and coagulation.
Conclusions:
- Significant alterations in key cardiovascular protein abundance suggest their involvement in degenerative aortic stenosis pathogenesis.
- Further research is needed to elucidate the precise roles of these proteins.
- This understanding may pave the way for future therapeutic interventions to modulate the disease process.
Abstract:
Degenerative aortic stenosis is the most common worldwide cause of valve replacement. While it shares certain risk factors with coronary artery disease, it is not delayed or reversed by reducing exposure to risk factors (e.g., therapies that lower lipids). Therefore, it is necessary to better understand its pathophysiology for preventive measures to be taken. In this work, aortic valve samples were collected from 20 patients that underwent aortic valve replacement (55% males, mean age of 74 years) and 20 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry, and 35 protein species were clearly increased in aortic valves, including apolipoprotein AI, alpha-1-antitrypsin, serum albumin, lumican, alfa-1-glycoprotein, vimentin, superoxide dismutase Cu-Zn, serum amyloid P-component, glutathione S-transferase-P, fatty acid-binding protein, transthyretin, and fibrinogen gamma. By contrast, 8 protein species were decreased (transgelin, haptoglobin, glutathione peroxidase 3, HSP27, and calreticulin). All of the proteins identified play a significant role in cardiovascular processes, such as fibrosis, homeostasis, and coagulation. The significant changes observed in the abundance of key cardiovascular proteins strongly suggest that they can be involved in the pathogenesis of degenerative aortic stenosis. Further studies are warranted to better understand this process before we can attempt to modulate it.
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