Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives
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, le...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2077 |
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| author | Lejla Medzikovic Tara Azem Wasila Sun Parmis Rejali Leana Esdin Shadie Rahman Ateyeh Dehghanitafti Laila Aryan Mansoureh Eghbali |
| author_facet | Lejla Medzikovic Tara Azem Wasila Sun Parmis Rejali Leana Esdin Shadie Rahman Ateyeh Dehghanitafti Laila Aryan Mansoureh Eghbali |
| author_sort | Lejla Medzikovic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:03:23Z |
| format | Article |
| id | doaj.art-742377b5b0fc439cbdbf4cd4d22d2664 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:03:23Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-742377b5b0fc439cbdbf4cd4d22d26642023-11-19T00:37:08ZengMDPI AGCells2073-44092023-08-011216207710.3390/cells12162077Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical PerspectivesLejla Medzikovic0Tara Azem1Wasila Sun2Parmis Rejali3Leana Esdin4Shadie Rahman5Ateyeh Dehghanitafti6Laila Aryan7Mansoureh Eghbali8Department 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USAMortality 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.https://www.mdpi.com/2073-4409/12/16/2077drugsmyocardial infarctionischemia reperfusion injurysex differences |
| spellingShingle | Lejla Medzikovic Tara Azem Wasila Sun Parmis Rejali Leana Esdin Shadie Rahman Ateyeh Dehghanitafti Laila Aryan Mansoureh Eghbali Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives Cells drugs myocardial infarction ischemia reperfusion injury sex differences |
| title | Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives |
| title_full | Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives |
| title_fullStr | Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives |
| title_full_unstemmed | Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives |
| title_short | Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives |
| title_sort | sex differences in therapies against myocardial ischemia reperfusion injury from basic science to clinical perspectives |
| topic | drugs myocardial infarction ischemia reperfusion injury sex differences |
| url | https://www.mdpi.com/2073-4409/12/16/2077 |
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