Valvular myofibroblast activation by transforming growth factor-beta: implications for pathological extracellular matrix remodeling in heart valve disease

Circulation Research
Gennyne A WalkerLeslie A Leinwand

Abstract

The pathogenesis of cardiac valve disease correlates with the emergence of muscle-like fibroblasts (myofibroblasts). These cells display prominent stress fibers containing alpha-smooth muscle actin (alpha-SMA) and are believed to differentiate from valvular interstitial cells (VICs). However, the biological factors that initiate myofibroblast differentiation and activation in valves remain unidentified. We show that transforming growth factor-beta1 (TGF-beta1) mediates differentiation of VICs into active myofibroblasts in vitro in a dose-dependent manner, as determined by a significant increase in alpha-SMA and the dramatic augmentation of stress fiber formation and alignment. Additionally, TGF-beta1 and increased mechanical stress function synergistically to enhance contractility. In turn, contractile valve myofibroblasts exert tension on the extracellular matrix, resulting in a dramatic realignment of extracellular fibronectin fibrils. TGF-beta1 also inhibits valve myofibroblast proliferation without enhancing apoptosis. Our results are consistent with activation of a highly contractile myofibroblast phenotype by TGF-beta1 and are the first to connect valve myofibroblast contractility with pathological valve matrix remodeling...Continue Reading

References

Dec 1, 1987·Journal of Molecular and Cellular Cardiology·C M JohnsonS C Helgeson
Nov 1, 1980·Cell·T E Kreis, W Birchmeier
Feb 1, 1994·The Journal of Cell Biology·F Grinnell
May 1, 1994·The Journal of Clinical Investigation·K E WatsonL L Demer
Jul 1, 1996·Pathology, Research and Practice·G Gabbiani
Jul 1, 1996·The International Journal of Biochemistry & Cell Biology·L C KatwaK T Weber
Apr 10, 1997·Experimental Cell Research·P G SmithL Kogerman
Jul 1, 1997·Journal of Molecular and Cellular Cardiology·S E Campbell, L C Katwa
Feb 12, 1998·The Journal of Cell Biology·D C Mayer, L A Leinwand
Jul 17, 1999·The American Journal of Physiology·D W PowellA B West
Jul 22, 1999·Experimental Cell Research·G Serini, G Gabbiani
Feb 19, 2000·Current Opinion in Cell Biology·D R Critchley
Oct 29, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·R G Wells
Mar 10, 2001·Current Topics in Developmental Biology·G A WalkerL A Leinwand
Apr 13, 2001·Journal of the American College of Cardiology·J FielitzV Regitz-Zagrosek
Jun 16, 2001·The Journal of Pathology·Y SoiniH Autio-Harmainen
Sep 13, 2001·Molecular Biology of the Cell·B HinzC Chaponnier
Apr 6, 2002·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Adam D Durbin, Avrum I Gotlieb
May 4, 2002·Nature Reviews. Molecular Cell Biology·James J TomasekRobert A Brown
Dec 3, 2002·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Elena Rabkin, Frederick J Schoen
Dec 14, 2002·The International Journal of Biochemistry & Cell Biology·Patricia M TaylorMagdi H Yacoub
Oct 15, 2003·The Journal of Cell Biology·Nancy A Rice, Leslie A Leinwand
May 1, 1997·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·D L Mulholland MSc, A I Gotlieb Md Cm Frcp

❮ Previous
Next ❯

Citations

Sep 4, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Daihiko HakunoKeiichi Fukuda
Mar 21, 2009·Cell and Tissue Research·Manuela Voinea CalinMaya Simionescu
Sep 29, 2011·Cell and Tissue Research·Thomas DoetschmanMohamad Azhar
Feb 7, 2012·Biomechanics and Modeling in Mechanobiology·Charles I FisherW David Merryman
Oct 21, 2006·Annals of Biomedical Engineering·Karen Mendelson, Frederick J Schoen
Dec 17, 2009·Annals of Biomedical Engineering·Jeffrey JohnKristen Billiar
Jul 28, 2010·Annals of Biomedical Engineering·Janet E BarzillaK Jane Grande-Allen
Aug 29, 2013·Annals of Biomedical Engineering·Emily J Farrar, Jonathan T Butcher
Jul 27, 2007·Cell Biochemistry and Biophysics·Shelly R PeytonAndrew J Putnam
Apr 23, 2013·Cell Biochemistry and Biophysics·Luigi Michele Pavone, Russell A Norris
Aug 18, 2012·Journal of Cardiovascular Translational Research·Eric M Small
Jun 29, 2007·Tissue Engineering·W David MerrymanMichael S Sacks
Jul 19, 2006·Tissue Engineering·Chrysanthi WilliamsRobert T Tranquillo
May 24, 2007·Tissue Engineering·Antonios G MikosGordana Vunjak-Novakovic
Jul 1, 2009·Tissue Engineering. Part a·Andrew J E AppletonKem A Rogers
Jan 26, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melinda C CushingKristi S Anseth
Nov 17, 2009·Journal of Veterinary Internal Medicine·M A Oyama, R J Levy
Aug 21, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Elyssa L Monzack, Kristyn S Masters
Dec 7, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Xiaoxiao Gu, Kristyn S Masters
Sep 14, 2007·Cells, Tissues, Organs·Tracy L BlevinsK Jane Grande-Allen
Nov 22, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Elyssa L MonzackKristyn S Masters
Aug 15, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Julie A BentonKristi S Anseth
Nov 20, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Joshua D HutchesonW David Merryman
Dec 5, 2009·Circulation Research·Colby A SoudersTroy A Baudino
May 28, 2011·Circulation Research·Jordan D MillerDonald D Heistad
Oct 6, 2007·American Journal of Respiratory and Critical Care Medicine·Gerald S HoranShelia M Violette
Sep 5, 2012·Fibrogenesis & Tissue Repair·Dong FanZamaneh Kassiri
May 1, 2008·Future Cardiology·W David Merryman
Jun 12, 2010·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Elizabeth H StephensK Jane Grande-Allen
Aug 3, 2006·American Journal of Veterinary Research·Mark A Oyama, Sridar V Chittur
Oct 15, 2014·Nature Reviews. Cardiology·Huan WangKristi S Anseth
May 9, 2008·Regenerative Medicine·Francesco MignecoRavi K Birla
Jan 22, 2014·Nature Reviews. Cardiology·Joshua D HutchesonW David Merryman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis