ArticleJournal of the American College of Surgeons2012
The role of extracellular signal-related kinase during abdominal aortic aneurysm formation.
Article in Journal of the American College of Surgeons, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
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- Therapeutic Targeting of Signaling Pathways in Abdominal Aortic Aneurysm: From Pathogenesis to Precision Medicine.Drug design, development and therapy · 2025Review
- CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights fromFrontiers in immunology · 2024Article
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress.International journal of molecular sciences · 2023Article
- Promising Novel Therapies in the Treatment of Aortic and Visceral Aneurysms.Journal of clinical medicine · 2023Review
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- Sodium Nitroprusside Stimulation of Elastic Matrix Regeneration by Aneurysmal Smooth Muscle Cells.Tissue engineering. Part A · 2023Article
- Targeting Epidermal Growth Factor Receptor to Stimulate Elastic Matrix Regenerative Repair.Tissue engineering. Part A · 2023Article
- Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?International journal of molecular sciences · 2023Review
- Repeated Social Defeat Enhances CaClCells · 2022Article
- Through network pharmacology and molecular docking to explore the underlying mechanism ofFrontiers in physiology · 2022Article
- The Important Role of Endothelium and Extracellular Vesicles in the Cellular Mechanism of Aortic Aneurysm Formation.International journal of molecular sciences · 2021Review
- Low glucose and serum levels cause an increased inflammatory factor in 3T3-L1 cell through Akt, MAPKs and NF-кB activation.Adipocyte · 2021Article
- POU class 2 homeobox associating factor 1 (POU2AF1) participates in abdominal aortic aneurysm enlargement based on integrated bioinformatics analysis.Bioengineered · 2021Article
- Lenvatinib halts aortic aneurysm growth by restoring smooth muscle cell contractility.JCI insight · 2021Article
- Testosterone Metabolite 6β-Hydroxytestosterone Contributes to Angiotensin II-Induced Abdominal Aortic Aneurysms inJournal of the American Heart Association · 2021Article
- Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm.Oxidative medicine and cellular longevity · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIt is hypothesized that activation of extracellular signal-related kinase (ERK) is critical in activating matrix metalloproteinases (MMPs) during abdominal aortic aneurysm (AAA) formation. STUDY
designC57BL/6 male mice underwent either elastase or heat-inactivated elastase aortic perfusion (n = 9 per group). Mouse aortic smooth muscle cells were transfected with ERK-1 and 2 siRNA along with or without elastase treatment. Mouse and human aortic tissue were analyzed by Western blots, zymograms, and immunohistochemistry, and statistical analysis was done using Graphpad and Image J softwares.
resultsWestern blot and immunohistochemistry documented increased phospho-mitogen-activated protein kinase kinase-1/2 (pMEK-1/2; 153%, p = 0.270 by Western) and pERK (171%, p = 0.004 by Western blot) in the elastase perfused aortas. Male ERK-1(-/-) mice underwent elastase perfusion, and aortic diameter was determined at day 14. ERK-1(-/-) mice failed to develop AAA, and histologic analysis depicted intact collagen and elastin fibers in the aortas. Zymography of aortas of elastase-treated ERK-1(-/-) mice showed lower levels of proMMP2 (p < 0.005) and active MMP2 (p < 0.0001), as well as proMMP9 (p = 0.037) compared with C57BL/6 mice. siRNA transfection of ERK-1 and -2 significantly reduced formation of pro- and active MMP2 (p < 0.01 for both isoforms) in aortic smooth muscle cells treated with elastase in vitro. Human AAA tissue had significantly elevated levels of pMEK-1/2 (150%, p = 0.014) and pERK (159%, p = 0.013) compared with control tissues.
conclusionsThe MAPK (mitogen-activated protein kinase)/ERK pathway is an important modulator of MMPs during AAA formation. Targeting the ERK pathway by reagents that inhibit either the expression or phosphorylation of ERK isoforms could be a potential therapy to prevent AAA formation.
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