UNRAVELLING SEX-DEPENDENT MECHANISMS IN CALCIFIC AORTIC VALVE STENOSIS
type: CreativeWork
description: Calcific aortic valve stenosis (CAVS) is the most common form of heart valve disease and affects about 3% of the population. Its prevalence increases with age, without a causal relation between ageing and CAVS development. To date, CAVS is a slow, progressive, multifactorial disorder considered to be actively driven by several cellular and molecular processes. Its natural history consists of a long clinically silent phase of non-uniform leaflet thickening with or without minimal calcification, known as aortic valve sclerosis (AVSc), without significant obstruction of blood flow, followed by the symptomatic stage, the aortic valve stenosis (AS). Currently, there is no pharmacological therapy preventing CAVS progression nor treating patients with AS. As a result, surgical or percutaneous aortic valve replacement remain the only treatments for severe AS, leaving the pathological molecular and cellular mechanisms unsolved. One of the first trigger of the pathology due to the oxidative stress is the endothelial dysfunction, followed by local inflammation and interstitial cells (VIC) differentiation into myofibroblasts and osteoblasts. Activated valve endothelial cells, undergoing endothelial to mesenchymal transition (EndMT), begin to express mesenchymal adhesion molecules and facilitate monocytes infiltration and local inflammation. These environmental changes induce VIC trans-differentiation into myofibroblast- and osteoblast-like cells. Activated VICs carry out a progressive extracellular matrix (ECM) pathological rearrangement characterized by the activation of fibrosis and calcification processes, which ultimately drive to fibro-calcific deposit formation. In the last years different studies reported sex-related difference in molecular mechanisms in the context of CAVS. In particular, it was shown that men with AS show a higher aortic valve calcium (AVC) load than women. Recently, it has been described that woman aortic valve leaflets were more fibrotic than man one…
abstract: Calcific aortic valve stenosis (CAVS) is the most common form of heart valve disease and affects about 3% of the population. Its prevalence increases with age, without a causal relation between ageing and CAVS development. To date, CAVS is a slow, progressive, multifactorial disorder considered to be actively driven by several cellular and molecular processes. Its natural history consists of a long clinically silent phase of non-uniform leaflet thickening with or without minimal calcification, known as aortic valve sclerosis (AVSc), without significant obstruction of blood flow, followed by the symptomatic stage, the aortic valve stenosis (AS). Currently, there is no pharmacological therapy preventing CAVS progression nor treating patients with AS. As a result, surgical or percutaneous aortic valve replacement remain the only treatments for severe AS, leaving the pathological molecular and cellular mechanisms unsolved. One of the first trigger of the pathology due to the oxidative stress is the endothelial dysfunction, followed by local inflammation and interstitial cells (VIC) differentiation into myofibroblasts and osteoblasts. Activated valve endothelial cells, undergoing endothelial to mesenchymal transition (EndMT), begin to express mesenchymal adhesion molecules and facilitate monocytes infiltration and local inflammation. These environmental changes induce VIC trans-differentiation into myofibroblast- and osteoblast-like cells. Activated VICs carry out a progressive extracellular matrix (ECM) pathological rearrangement characterized by the activation of fibrosis and calcification processes, which ultimately drive to fibro-calcific deposit formation. In the last years different studies reported sex-related difference in molecular mechanisms in the context of CAVS. In particular, it was shown that men with AS show a higher aortic valve calcium (AVC) load than women. Recently, it has been described that woman aortic valve leaflets were more fibrotic than man one…
author: MOSCHETTA, DONATO
language: eng
keywords: CAVS, AORTIC VALVE, SEX-DIFFERENCES, AORTIC VALVE STENOSIS, Settore BIO/14 - Farmacologia
date published: 2022-12-12
date modified: 2026-07-27T20:18:46Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/947275

PropertyValue
property ID: DOI
value: 10.13130/moschetta-donato_phd2022-12-12