Novel therapeutic strategies for cardioprotection.
The morbidity and mortality from ischemic heart disease (IHD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of occluded coronary arteries. Although it is essential to re-open the artery as soon as possible, paradoxically this leads to additional myocardial injury, called acute ischemia-reperfusion injury (IRI), for which currently no effective therapy is available. Therefore, novel therapeutic strategies are required to protect the heart from acute IRI in order to reduce myocardial infarction size, preserve cardiac function and improve clinical outcomes in patients with IHD. In this review article, we will first outline the pathophysiology of acute IRI and review promising therapeutic strategies for cardioprotection. These include novel aspects of mitochondrial function, epigenetics, circadian clocks, the immune system, microvesicles, growth factors, stem cell therapy and gene therapy. We discuss the therapeutic potential of these novel cardioprotective strategies in terms of pharmacological targeting and clinical application.
Department of Cardiology, University Medical Center Utrecht, The Netherlands; ICIN, Netherlands Heart Institute, Utrecht, The Netherlands.
Joost P G
JP
Sluijter
Humanitas Research Hospital, University of Milan, Rozzano, MI, Italy.
Gianluigi
G
Condorelli
The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
Sean M
SM
Davidson
Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany.
Felix B
FB
Engel
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary.
Peter
P
Ferdinandy
Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, South Africa.
Derek J
DJ
Hausenloy
Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, South Africa.
Sandrine
S
Lecour
Department of Neurosciences and Imaging, Institute of Cardiology, University of Chieti, Chieti, Italy.
Rosalinda
R
Madonna
Service d'Explorations Fonctionnelles Cardiovasculaires, Hôpital Louis Pradel, France; Inserm U1060-CarMeN, CIC de Lyon, Université Claude Bernard Lyon, Lyon, France.
Michel
M
Ovize
Laboratori Cardiologia, Vall d'Hebron Institut de Recerca, Universitat Autonoma de Barcelona, Spain.
Marisol
M
Ruiz-Meana
Physiologisches Institut, Justus-Liebig Universität, Gießen, Germany.
Rainer
R
Schulz
Department of Cardiology, University Medical Center Utrecht, The Netherlands. Electronic address: l.w.vanlaake@umcutrecht.nl.
Linda W
LW
Van Laake
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D057906:Circadian Clocks / Q000502:physiology; D044127:Epigenesis, Genetic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods
D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins
Cardioprotection; Circadian clock; Growth factors; Ischemia–reperfusion injury; Microvesicles; Mitochondria