Proteomic Profile of Human
Aortic Stenosis: Insights
into the Degenerative Process
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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