Valvular Aortic Stenosis: A Proteomic Insight

Abstract

Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area.Summary:Until recently, aortic stenosis (AS) was considered a passive process secondary to calcium deposition in the aortic valves. However, it has recently been highlighted that the risk factors associated with the development of calcified AS in the elderly are similar to those of coronary artery disease. Furthermore, degenerative AS shares histological characteristics with atherosclerotic plaques, leading to the suggestion that calcified aortic valve disease is a chronic inflammatory process similar to atherosclerosis. Nevertheless, certain data does not fit with this theory making it necessary to further study this pathology. The aim of this study is to develop an effective protein extraction protocol for aortic stenosis valves such that proteomic analyses can be performed on these structures. In the present work we have defined a rapid, reproducible and effective method to extract proteins and that is compatible with 2-DE, 2D-DIGE and MS techniques. Defining the protein profile of this tissue is an important and challenging task that will help to understand the mechanisms of physiological/pathological processes in aortic stenosis valves.

A clinical perspective on the utility of alpha 1 antichymotrypsin for the early diagnosis of calcific aortic stenosis

“…For 2D-DIGE and western blotting, one aortic valve leaflet was ground into a powder in liquid N 2 in a mortar. Protein extracts were then prepared from the valve as described previously [ 8 , 9 ] and the total protein concentration was measured by the Bradford-Lowry method (Bio-Rad protein assay) [ 10 ].…”

Potential blood biomarkers for stroke

“…Although proteomic studies of human diseases mainly focus on the most interesting biological samples from a clinical perspective (blood and urine), there have also been very interesting studies carried out on samples of different natures, such as tissue, cell cultures and secretome, that have been developed in other diseases [45][46][47][48][49][50][51][52][53] .…”

Tfe3 and Tfeb Transcriptionally Regulate Peroxisome Proliferator-Activated Receptor γ2 Expression in Adipocytes and Mediate Adiponectin and Glucose Levels in Mice

“…1C) were also examined and found to be affected by fasting and refeeding, specifically in BAT and WAT. Fasting decreases and refeeding elevates levels of Ppar␥2 expression, an effect described previously (27,34). The high expression of Tfe3 and Tfeb in WAT prompted us to investigate their role during adipocyte differentiation.…”