Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes
Matrix metalloproteinases (MMPs) are a family of enzymes that play an important role in the pathophysiology of hypertensive disorders, particularly through their involvement in extracellular matrix (ECM) remodeling and vascular dysfunction. Their activity is closely linked to hypertension-mediated o...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1559288/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849729860364140544 |
|---|---|
| author | Soroush Taherkhani Mohammad Sheibani Mohammad Sheibani Ali Mohammadkhanizadeh Jitka A. I. Virag Lisandra de Castro Braz Yaser Azizi |
| author_facet | Soroush Taherkhani Mohammad Sheibani Mohammad Sheibani Ali Mohammadkhanizadeh Jitka A. I. Virag Lisandra de Castro Braz Yaser Azizi |
| author_sort | Soroush Taherkhani |
| collection | DOAJ |
| description | Matrix metalloproteinases (MMPs) are a family of enzymes that play an important role in the pathophysiology of hypertensive disorders, particularly through their involvement in extracellular matrix (ECM) remodeling and vascular dysfunction. Their activity is closely linked to hypertension-mediated organ damage, which affects the vascular and cardio-renal systems. MMPs are responsible for degrading various components of the ECM, which is crucial for maintaining vascular structure and function. In hypertensive patients, several MMPs, including MMP-1, MMP-3, and MMP-9, are often found at elevated levels. This is associated with vascular remodeling and dysfunction due to chronic high blood pressure. The activation of MMPs in hypertension can be triggered by several factors, such as oxidative stress, inflammatory cytokines, and vasoactive agents like angiotensin II. In addition to increasing MMP activity, these variables cause an imbalance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are the MMPs’ natural inhibitors. This imbalance contributes to excessive degradation of the ECM and promotes pathological changes in vascular smooth muscle cells (VSMCs), leading to their transition from a contractile to a synthetic phenotype. This shift facilitates cell growth and migration, exacerbating vascular remodeling. Given their critical roles in hypertension-related organ damage, MMPs are being explored as potential pharmacological targets. Inhibitors of MMPs may help mitigate the adverse effects of hypertension by restoring balance in ECM remodeling processes. Understanding their mechanisms opens avenues for targeted therapies that could significantly improve outcomes for individuals suffering from hypertension-related complications. |
| format | Article |
| id | doaj-art-305dc8e18da04e54a68d125eeeae8db2 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-305dc8e18da04e54a68d125eeeae8db22025-08-20T03:09:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15592881559288Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changesSoroush Taherkhani0Mohammad Sheibani1Mohammad Sheibani2Ali Mohammadkhanizadeh3Jitka A. I. Virag4Lisandra de Castro Braz5Yaser Azizi6Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranRazi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology, East Carolina University, Greenville, NC, United StatesDepartment of Physiology, East Carolina University, Greenville, NC, United StatesDepartment of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranMatrix metalloproteinases (MMPs) are a family of enzymes that play an important role in the pathophysiology of hypertensive disorders, particularly through their involvement in extracellular matrix (ECM) remodeling and vascular dysfunction. Their activity is closely linked to hypertension-mediated organ damage, which affects the vascular and cardio-renal systems. MMPs are responsible for degrading various components of the ECM, which is crucial for maintaining vascular structure and function. In hypertensive patients, several MMPs, including MMP-1, MMP-3, and MMP-9, are often found at elevated levels. This is associated with vascular remodeling and dysfunction due to chronic high blood pressure. The activation of MMPs in hypertension can be triggered by several factors, such as oxidative stress, inflammatory cytokines, and vasoactive agents like angiotensin II. In addition to increasing MMP activity, these variables cause an imbalance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are the MMPs’ natural inhibitors. This imbalance contributes to excessive degradation of the ECM and promotes pathological changes in vascular smooth muscle cells (VSMCs), leading to their transition from a contractile to a synthetic phenotype. This shift facilitates cell growth and migration, exacerbating vascular remodeling. Given their critical roles in hypertension-related organ damage, MMPs are being explored as potential pharmacological targets. Inhibitors of MMPs may help mitigate the adverse effects of hypertension by restoring balance in ECM remodeling processes. Understanding their mechanisms opens avenues for targeted therapies that could significantly improve outcomes for individuals suffering from hypertension-related complications.https://www.frontiersin.org/articles/10.3389/fphar.2025.1559288/fullMMPsECMhypertensive disordersvascular remodelingTIMPs |
| spellingShingle | Soroush Taherkhani Mohammad Sheibani Mohammad Sheibani Ali Mohammadkhanizadeh Jitka A. I. Virag Lisandra de Castro Braz Yaser Azizi Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes Frontiers in Pharmacology MMPs ECM hypertensive disorders vascular remodeling TIMPs |
| title | Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes |
| title_full | Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes |
| title_fullStr | Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes |
| title_full_unstemmed | Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes |
| title_short | Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes |
| title_sort | metalloproteinases mmps in hypertensive disorders role function pharmacology and potential strategies to mitigate pathophysiological changes |
| topic | MMPs ECM hypertensive disorders vascular remodeling TIMPs |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1559288/full |
| work_keys_str_mv | AT soroushtaherkhani metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT mohammadsheibani metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT mohammadsheibani metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT alimohammadkhanizadeh metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT jitkaaivirag metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT lisandradecastrobraz metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges AT yaserazizi metalloproteinasesmmpsinhypertensivedisordersrolefunctionpharmacologyandpotentialstrategiestomitigatepathophysiologicalchanges |