Calpain inhibition preserves talin and attenuates right heart failure in acute pulmonary hypertension.

American Journal of Respiratory Cell and Molecular Biology
Hasan AhmadC Greyson

Abstract

Right heart failure from right ventricular (RV) pressure overload is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We tested the hypothesis that right heart failure during 4 hours of RV pressure overload is associated with alterations of the focal adhesion protein talin, and that the inhibition of calpain attenuates RV dysfunction and preserves RV talin. Anesthetized open-chest pigs treated with the calpain inhibitor MDL-28170 (n = 20) or inactive vehicle (n = 23) underwent 4 hours of RV pressure overload by pulmonary artery constriction (initial RV systolic pressure, 64 ± 1 and 66 ± 1 mm Hg in MDL-28170 and vehicle-treated pigs, respectively). Progressive RV contractile dysfunction was attenuated by MDL-28170: after 4 hours of RV pressure overload, RV systolic pressure was 44 ± 4 mm Hg versus 49 ± 6 mm Hg (P = 0.011), and RV stroke work was 72 ± 5% of baseline versus 90 ± 5% of baseline, (P = 0.027), in vehicle-treated versus MDL-28170-treated pigs, respectively. MDL-28170 reduced the incidence of hemodynamic instability (death or systolic blood pressure of < 85 mm Hg) by 46% (P = 0.013). RV pressure overload disrupted talin organization. MDL-28170 preserved talin abundance in the RV f...Continue Reading

References

Sep 1, 1992·The Journal of Cell Biology·B A DanowskiJ W Sanger
Oct 1, 1991·Current Problems in Cardiology·L J Dell'Italia
Apr 1, 1991·Trends in Biochemical Sciences·S Mehdi
Dec 30, 1988·Biochemical and Biophysical Research Communications·S MehdiP Bey
Nov 3, 1998·Cell and Tissue Research·S KostinJ Schaper
Oct 26, 1999·Cardiovascular Research·D E Euler
Apr 25, 2000·American Journal of Physiology. Heart and Circulatory Physiology·C GreysonG G Schwartz
Dec 21, 2000·American Journal of Physiology. Heart and Circulatory Physiology·Y G WangS L Lipsius
Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·T TsujiM Takaki
Oct 5, 2001·Journal of the American College of Cardiology·B Stobierska-DzierzekR E Michler
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Apr 9, 2004·Critical Care Medicine·François KerbaulSerge Brimioulle
Jul 14, 2004·Cardiovascular Research·David A ColantonioKarin Przyklenk
Aug 21, 2004·Advances in Physiology Education·Douglas Curran-Everett, Dale J Benos
Sep 28, 2004·Nature Cell Biology·Santos J FrancoAnna Huttenlocher
Dec 2, 2004·The Thoracic and Cardiovascular Surgeon·C MühlfeldF Schoendube
Feb 10, 2006·Cardiovascular Research·Mara BrancaccioGuido Tarone
Feb 13, 2007·Trends in Cardiovascular Medicine·Ahlke Heydemann, Elizabeth M McNally
Dec 11, 2007·Journal of Molecular and Cellular Cardiology·Clifford R GreysonHasan Ahmad
May 20, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Santhosh K ManiDhandapani Kuppuswamy
Jun 17, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·R A BemG Matute-Bello
Jan 2, 2009·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Jan D SchmittoFriedrich A Schoendube
Jan 14, 2009·Blood Reviews·Sarah B MurthiJohn R Hess
Mar 31, 2009·American Journal of Respiratory Cell and Molecular Biology·Gerald S Supinski, Leigh Ann Callahan
Feb 13, 2010·The Journal of Biological Chemistry·Keefe T ChanAnna Huttenlocher
May 1, 2010·Critical Care Medicine·Céline DewachterRobert Naeije

❮ Previous
Next ❯

Citations

Nov 16, 2013·International Journal of Molecular Sciences·Martin L Pall
Oct 20, 2015·The Journal of Thoracic and Cardiovascular Surgery·Ashraf A SabeFrank W Sellke
Nov 3, 2020·Frontiers in Cardiovascular Medicine·Jonathan J EdwardsZoltan Arany
Aug 17, 2021·Oxidative Medicine and Cellular Longevity·Rubin TanJie Cui

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.

Related Papers

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Angelina VassilevaAmando Gamba
ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Geetha Bhat, Alex Costea
© 2021 Meta ULC. All rights reserved