TGF-beta1 pathway activation and adherens junction molecular pattern in nonsyndromic mitral valve prolapse

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
Stefania RizzoKalliopi Pilichou

Abstract

Dysregulation of the transforming growth factor beta (TGF-β) 1 pathway has been associated with either syndromic or isolated mitral valve (MV) prolapse due to myxoid degeneration (floppy MV). The activation of Smad receptor-mediated intracellular TGF-β pathway and its effect on adherens junction (AJ) molecular pattern of activated valvular interstitial cells (VICs) in MV prolapse are herein investigated. Floppy MV leaflets were obtained from 30 patients (24 males, mean age 55.5±12.7 years) who underwent surgical repair, and 10 age- and sex-matched Homograft Tissue Bank samples served as controls. MV leaflet cellular and extracellular matrix composition, including collagen I and III, was evaluated by histology and transmission electron microscopy. Smad2 active phosphorylated form (p-Smad2), α-smooth muscle actin (α-SMA), and junctional proteins (N-cadherin, cadherin-11, β-catenin, plakoglobin, plakophilin-2) in VICs were assessed by immunohistochemistry and immunofluorescence and confirmed by immunoblotting. Quantitative real-time polymerase chain reaction was carried out for components of TGF-β pathway cascade and filamin A (FLN-A). Floppy MV leaflets were thicker (P<.001) and had higher α-SMA+ cell density (P=.002) and collage...Continue Reading

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Citations

Jun 1, 2016·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Frederick J Schoen, Avrum I Gotlieb
Sep 23, 2016·International Journal of Legal Medicine·Antonio OlivaRamon Brugada
Oct 19, 2017·European Heart Journal·Gaetano Thiene, Cristina Basso
Jan 10, 2018·Frontiers in Cardiovascular Medicine·Leah A Pagnozzi, Jonathan T Butcher
Aug 10, 2016·Cardiovascular Engineering and Technology·Frederick J Schoen
Nov 30, 2018·Expert Review of Cardiovascular Therapy·Aeshah AlthunayyanSanjeev Bhattacharyya
Sep 10, 2019·Circulation·Cristina BassoMartina Perazzolo Marra
Jun 23, 2021·Journal of the American Heart Association·Jordan E MorningstarRussell A Norris

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