Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives
Lejla Medzikovic,
Tara Azem,
Wasila Sun,
Parmis Rejali,
Leana Esdin,
Shadie Rahman,
Ateyeh Dehghanitafti,
Laila Aryan,
Mansoureh Eghbali
Affiliations
Lejla Medzikovic
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Tara Azem
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Wasila Sun
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Parmis Rejali
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Leana Esdin
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Shadie Rahman
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Ateyeh Dehghanitafti
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Laila Aryan
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Mansoureh Eghbali
Department of Anesthesiology & Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, CHS BH-550 CHS, Los Angeles, CA 90095, USA
Mortality from myocardial infarction (MI) has declined over recent decades, which could be attributed in large part to improved treatment methods. Early reperfusion is the cornerstone of current MI treatment. However, reoxygenation via restored blood flow induces further damage to the myocardium, leading to ischemia-reperfusion injury (IRI). While experimental studies overwhelmingly demonstrate that females experience greater functional recovery from MI and decreased severity in the underlying pathophysiological mechanisms, the outcomes of MI with subsequent reperfusion therapy, which is the clinical correlate of myocardial IRI, are generally poorer for women compared with men. Distressingly, women are also reported to benefit less from current guideline-based therapies compared with men. These seemingly contradicting outcomes between experimental and clinical studies show a need for further investigation of sex-based differences in disease pathophysiology, treatment response, and a sex-specific approach in the development of novel therapeutic methods against myocardial IRI. In this literature review, we summarize the current knowledge on sex differences in the underlying pathophysiological mechanisms of myocardial IRI, including the roles of sex hormones and sex chromosomes. Furthermore, we address sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics of current drugs prescribed to limit myocardial IRI. Lastly, we highlight ongoing clinical trials assessing novel pharmacological treatments against myocardial IRI and sex differences that may underlie the efficacy of these new therapeutic approaches.
