Mitochondrial Membrane Permeability Inhibitors in Acute Myocardial Infarction: Still Awaiting Translation

JACC. Basic to Translational Science
Cory TrankleAntonio Abbate

Abstract

Despite therapeutic advances, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. One potential limitation of the current treatment paradigm is the lack of effective therapies to optimize reperfusion after ischemia and prevent reperfusion-mediated injury. Experimental studies indicate that this process accounts for up to 50% of the final infarct size, lending it importance as a potential target for cardioprotection. However, multiple therapeutic approaches have shown potential in pre-clinical and early phase trials but a paucity of clear clinical benefit when expanded to larger studies. Here we explore this history of trials and errors of the studies of cyclosporine A and other mitochondrial membrane permeability inhibitors, agents that appeared to have a promising pre-clinical record yet provided disappointing results in phase III clinical trials.

References

Jul 1, 1979·Archives of Biochemistry and Biophysics·D R Hunter, R A Haworth
Dec 1, 1991·Journal of Molecular and Cellular Cardiology·W NazarethM Crompton
Nov 1, 1985·The Journal of Clinical Investigation·E Braunwald, R A Kloner
Dec 1, 1993·Journal of Molecular and Cellular Cardiology·E J Griffiths, A P Halestrap
Apr 1, 1995·The Biochemical Journal·E J Griffiths, A P Halestrap
Jun 10, 2005·Basic Research in Cardiology·A J BullardD M Yellon
Apr 13, 2007·Coronary Artery Disease·Janghyun ChoMun K Hong
Jun 15, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Ludovic GomezMichel Ovize
Jun 15, 2007·Journal of Cardiovascular Pharmacology and Therapeutics·Joan Dow, Robert A Kloner
Aug 21, 2007·Journal of the American College of Cardiology·Ellis F Unger
Sep 15, 2007·The New England Journal of Medicine·Derek M Yellon, Derek J Hausenloy
Aug 2, 2008·The New England Journal of Medicine·Christophe PiotMichel Ovize
Aug 2, 2008·The New England Journal of Medicine·Derek J Hausenloy, Derek M Yellon
Oct 29, 2008·Circulation·Raghava S VelagaletiRamachandran S Vasan
Apr 8, 2009·Circulation·Joseph Loscalzo
Mar 11, 2010·The Journal of Pharmacology and Experimental Therapeutics·Sophie SchallerRebecca M Pruss
May 4, 2010·Journal of Cardiovascular Pharmacology and Therapeutics·Lars O KarlssonLars Grip
Aug 31, 2010·European Heart Journal·Adriaan A VoorsUNKNOWN HEBE III Investigators
May 17, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Meimei YinRudolf A de Boer
May 17, 2011·Journal of Cardiovascular Pharmacology and Therapeutics·Lars O KarlssonLars Grip
Jan 3, 2013·The Journal of Clinical Investigation·Derek J Hausenloy, Derek M Yellon
Aug 3, 2013·Circulation Research·Richard S Vander Heide, Charles Steenbergen
Aug 21, 2013·Basic Research in Cardiology·Damien De PaulisMichel Ovize
Sep 6, 2013·The New England Journal of Medicine·Daniel S MeneesHitinder S Gurm
Nov 30, 2013·Journal of Cardiovascular Pharmacology and Therapeutics·David A BrownRobert A Kloner
Apr 2, 2014·JAMA : the Journal of the American Medical Association·Chris P H LexisUNKNOWN GIPS-III Investigators
Jul 23, 2014·Anesthesiology·Pascal ChiariMichel Ovize
Oct 1, 2014·Journal of Molecular and Cellular Cardiology·Paolo Bernardi, Fabio Di Lisa
Apr 11, 2015·Journal of the American College of Cardiology·Borja IbáñezFrans Van de Werf

❮ Previous
Next ❯

Citations

Sep 1, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Stefano ToldoAntonio Abbate
Dec 22, 2019·British Journal of Pharmacology·Marisol Ruiz-MeanaKirsti Ytrehus
Jan 31, 2019·International Journal of Molecular Sciences·Nicola PotereAntonio Abbate
Dec 21, 2019·Experimental & Molecular Medicine·Jessica N PeoplesJennifer Q Kwong
May 14, 2019·Frontiers in Cardiovascular Medicine·Nicola PotereStefano Toldo
Jul 25, 2017·Archives of Biochemistry and Biophysics·Sehwan Jang, Sabzali Javadov
May 18, 2021·Frontiers in Bioengineering and Biotechnology·Hye Sook ShinYasuhiro Shudo

❮ Previous
Next ❯

Methods Mentioned

BETA
coronary artery bypass

Software Mentioned

MITOCARE

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.