title: Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning.
abstract: Pre-, post-, and remote conditioning of the myocardium are well described adaptive responses that markedly enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and provide therapeutic paradigms for cardioprotection. Nevertheless, more than 25 years after the discovery of ischemic preconditioning, we still do not have established cardioprotective drugs on the market. Most experimental studies on cardioprotection are still undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of cardiovascular risk factors. However, ischemic heart disease in humans is a complex disorder caused by, or associated with, cardiovascular risk factors and comorbidities, including hypertension, hyperlipidemia, diabetes, insulin resistance, heart failure, altered coronary circulation, and aging. These risk factors induce fundamental alterations in cellular signaling cascades that affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Moreover, some of the medications used to treat these risk factors, including statins, nitrates, and antidiabetic drugs, may impact cardioprotection by modifying cellular signaling. The aim of this article is to review the recent evidence that cardiovascular risk factors and their medication may modify the response to cardioprotective interventions. We emphasize the critical need to take into account the presence of cardiovascular risk factors and concomitant medications when designing preclinical studies for the identification and validation of cardioprotective drug targets and clinical studies. This will hopefully maximize the success rate of developing rational approaches to effective cardioprotective therapies for the majority of patients with multiple risk factors.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.); Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged and Pharmahungary Group, Szeged, Hungary (P.F.); The Hatter Cardiovascular Institute, University College London, London, United Kingdom (D.J.H.); Institute for Pathophysiology, University of Essen Medical School, Essen, Germany (G.H.); Division of Pharmacology, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom (G.F.B.); and Institute of Physiology, Justus-Liebig University, Giessen, Germany (R.S.) peter.ferdinandy@pharmahungary.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.); Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged and Pharmahungary Group, Szeged, Hungary (P.F.); The Hatter Cardiovascular Institute, University College London, London, United Kingdom (D.J.H.); Institute for Pathophysiology, University of Essen Medical School, Essen, Germany (G.H.); Division of Pharmacology, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom (G.F.B.); and Institute of Physiology, Justus-Liebig University, Giessen, Germany (R.S.).
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.); Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged and Pharmahungary Group, Szeged, Hungary (P.F.); The Hatter Cardiovascular Institute, University College London, London, United Kingdom (D.J.H.); Institute for Pathophysiology, University of Essen Medical School, Essen, Germany (G.H.); Division of Pharmacology, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom (G.F.B.); and Institute of Physiology, Justus-Liebig University, Giessen, Germany (R.S.).
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.); Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged and Pharmahungary Group, Szeged, Hungary (P.F.); The Hatter Cardiovascular Institute, University College London, London, United Kingdom (D.J.H.); Institute for Pathophysiology, University of Essen Medical School, Essen, Germany (G.H.); Division of Pharmacology, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom (G.F.B.); and Institute of Physiology, Justus-Liebig University, Giessen, Germany (R.S.).
authors.forename: Gary F
authors.initials: GF
authors.lastname: Baxter
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.); Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged and Pharmahungary Group, Szeged, Hungary (P.F.); The Hatter Cardiovascular Institute, University College London, London, United Kingdom (D.J.H.); Institute for Pathophysiology, University of Essen Medical School, Essen, Germany (G.H.); Division of Pharmacology, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom (G.F.B.); and Institute of Physiology, Justus-Liebig University, Giessen, Germany (R.S.).
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D015195:Drug Design; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D058990:Molecular Targeted Therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents