ArticleJournal of the American Heart Association2013
SMAD3 deficiency promotes inflammatory aortic aneurysms in angiotensin II-infused mice via activation of iNOS.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
- Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro.International journal of molecular sciences · 2023Review
- Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.Journal of geriatric cardiology : JGC · 2023Article
- Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications.International journal of biological sciences · 2023Review
- Local Release of TGF-β Inhibitor Modulates Tumor-Associated Neutrophils and Enhances Pancreatic Cancer Response to Combined Irreversible Electroporation and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nicotine Affects Murine Aortic Stiffness and Fatigue Response During Supraphysiological Cycling.Journal of biomechanical engineering · 2022Article
- Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections.Frontiers in pharmacology · 2022Review
- Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2020Review
- CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.Circulation. Cardiovascular imaging · 2020Article
- Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm.BioMed research international · 2020Article
- Genes Associated with Thoracic Aortic Aneurysm and Dissection: 2019 Update and Clinical Implications.Aorta (Stamford, Conn.) · 2019Article
- Genomic Observations of a Rare/PathogenicMedicina (Kaunas, Lithuania) · 2019Article
- The Role of the TGF-β Superfamily in Myocardial Infarction.Frontiers in cardiovascular medicine · 2019Review
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- TGF-β Signaling in Control of Cardiovascular Function.Cold Spring Harbor perspectives in biology · 2018Review
- Genes Associated with Thoracic Aortic Aneurysm and Dissection: 2018 Update and Clinical Implications.Aorta (Stamford, Conn.) · 2018Article
- Identification of SMAD3 as a Novel Mediator of Inflammation in Human MyometriumMediators of inflammation · 2018Article
- Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.Cell discovery · 2018Article
- Monocytes and macrophages in abdominal aortic aneurysm.Nature reviews. Cardiology · 2017Review
- Anti-Atherosclerotic Potential of Aqueous Extract ofJournal of clinical and diagnostic research : JCDR · 2017Article
- Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNinety percent of the patients carrying distinct SMAD3 mutations develop aortic aneurysms and dissections, called aneurysms-osteoarthritis syndrome (AOS). However, the etiology and molecular events downstream of SMAD3 leading to the pathogenesis of aortic aneurysms in these patients still remain elusive. Therefore, we aimed to investigate the vascular phenotypes of SMAD3-knockout mice. METHODS AND
resultsWe have shown that angiotensin II-induced vascular inflammation, but not hypertension, leads to aortic aneurysms and dissections, ultimately causing aortic rupture and death in mice. Lipopolysaccharide-triggered inflammation confirmed that enhanced aortic macrophage recruitment was essential for aneurysm formation in angiotensin II-infused SMAD3-knockout mice. In contrast, phenylephrine-triggered hypertension alone was insufficient to induce aortic aneurysms in mice. Using uniaxial tensile and contractility tests, we showed that SMAD3 deficiency resulted in defective aortic biomechanics and physiological functions, which caused weakening of the aortic wall and predisposed the mice to aortic aneurysms. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that the underlying mechanism involved aberrant upregulation of inducible nitric oxide synthase (iNOS)-derived nitric oxide production and activation of elastolytic matrix metalloproteinases 2 and 9. Administration of clodronate-liposomes and iNOS inhibitor completely abrogated these aortic conditions, thereby identifying iNOS-mediated nitric oxide secretion from macrophages as the downstream event of SMAD3 that drives this severe pathology.
conclusionsMacrophage depletion and iNOS antagonism represent 2 promising approaches for preventing aortic aneurysms related to SMAD3 mutations and merit further investigation as adjunctive strategies for the life-threatening manifestations of AOS.
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