Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies
Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a pro...
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2025-06-01
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| author | Joy Das Ashok Kumar Sah Ranjay Kumar Choudhary Rabab H. Elshaikh Utpal Bhui Shreya Chowdhury Anass M. Abbas Manar G. Shalabi Nadeem Ahmad Siddique Raji Rubayyi Alshammari Navjyot Trivedi Khoula Salim Ali Buwaiqi Said Al Ghenaimi Pranav Kumar Prabhakar |
| author_facet | Joy Das Ashok Kumar Sah Ranjay Kumar Choudhary Rabab H. Elshaikh Utpal Bhui Shreya Chowdhury Anass M. Abbas Manar G. Shalabi Nadeem Ahmad Siddique Raji Rubayyi Alshammari Navjyot Trivedi Khoula Salim Ali Buwaiqi Said Al Ghenaimi Pranav Kumar Prabhakar |
| author_sort | Joy Das |
| collection | DOAJ |
| description | Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-9e0bb5b7d57841c9945e3cfba581bdf52025-08-20T04:00:54ZengMDPI AGBiomedicines2227-90592025-06-01137153210.3390/biomedicines13071532Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel TherapiesJoy Das0Ashok Kumar Sah1Ranjay Kumar Choudhary2Rabab H. Elshaikh3Utpal Bhui4Shreya Chowdhury5Anass M. Abbas6Manar G. Shalabi7Nadeem Ahmad Siddique8Raji Rubayyi Alshammari9Navjyot Trivedi10Khoula Salim Ali Buwaiqi11Said Al Ghenaimi12Pranav Kumar Prabhakar13School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, IndiaDepartment of Medical Laboratory Sciences, College of Applied & Health Sciences, A’ Sharqiyah University, Ibra 400, OmanDepartment of Medical Laboratory Technology, UIAHS University Institute of Allied Health Sciences, Chandigarh University, Mohali 140413, Punjab, IndiaDepartment of Medical Laboratory Sciences, College of Applied & Health Sciences, A’ Sharqiyah University, Ibra 400, OmanSchool of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, IndiaDepartment of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, BangladeshDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pharmaceutical Chemistry, University of Hafar Al Batin, Hafar Al-Batin 31991, Saudi ArabiaDepartment of Pharmacy Practice, University of Hafar Al Batin, Hafar Al-Batin 31991, Saudi ArabiaDepartment of Physiotherapy, University Institute of Allied Health Sciences, Chandigarh University, Mohali 140413, Punjab, IndiaResearch, Innovation and Technology Transfer Center, A’ Sharqiyah University, Ibra 400, OmanCollege of Applied and Health Sciences, A’ Sharqiyah University, Ibra 400, OmanDepartment of Biotechnology, School of Engineering and Technology, Nagaland University, Meriema, Kohima 797004, Nagaland, IndiaMyocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction.https://www.mdpi.com/2227-9059/13/7/1532myocardial infarctioncardiac reperfusion injuryoxidative stresscalcium overloadmitochondrial dysfunctionmolecular target |
| spellingShingle | Joy Das Ashok Kumar Sah Ranjay Kumar Choudhary Rabab H. Elshaikh Utpal Bhui Shreya Chowdhury Anass M. Abbas Manar G. Shalabi Nadeem Ahmad Siddique Raji Rubayyi Alshammari Navjyot Trivedi Khoula Salim Ali Buwaiqi Said Al Ghenaimi Pranav Kumar Prabhakar Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies Biomedicines myocardial infarction cardiac reperfusion injury oxidative stress calcium overload mitochondrial dysfunction molecular target |
| title | Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies |
| title_full | Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies |
| title_fullStr | Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies |
| title_full_unstemmed | Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies |
| title_short | Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies |
| title_sort | network pharmacology approaches to myocardial infarction reperfusion injury exploring mechanisms pathophysiology and novel therapies |
| topic | myocardial infarction cardiac reperfusion injury oxidative stress calcium overload mitochondrial dysfunction molecular target |
| url | https://www.mdpi.com/2227-9059/13/7/1532 |
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