ArticleScience translational medicine2013
Angiotensin-converting enzyme-induced activation of local angiotensin signaling is required for ascending aortic aneurysms in fibulin-4-deficient mice.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 52 citations in OpenAlex.
- IL-6/gp130 signaling in CD4Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.Journal of the American Heart Association · 2023Article
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- Fibulin-3 Deficiency Protects Against Myocardial Injury Following Ischaemia/ Reperfusion inFrontiers in cardiovascular medicine · 2022Article
- Postnatal Smad3 Inactivation in Murine Smooth Muscle Cells Elicits a Temporally and Regionally Distinct Transcriptional Response.Frontiers in cardiovascular medicine · 2022Article
- Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment.Cardiovascular drugs and therapy · 2021Review
- Review
- MiR-126a-5p limits the formation of abdominal aortic aneurysm in mice and decreases ADAMTS-4 expression.Journal of cellular and molecular medicine · 2020Article
- Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.Journal of the American Heart Association · 2020Article
- Angiotensin I Infusion Reveals Differential Effects of Angiotensin-Converting Enzyme in Aortic Resident Cells on Aneurysm Formation.Circulation journal : official journal of the Japanese Circulation Society · 2020Article
- Captopril treatment during development alleviates mechanically induced aortic remodeling in newborn elastin knockout mice.Biomechanics and modeling in mechanobiology · 2020Article
- Inflammation in thoracic aortic aneurysms.Herz · 2019Article
- Reversal of Aortic Enlargement Induced by Increased Biomechanical Forces Requires AT1R Inhibition in Conjunction With AT2R Activation.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Therapies for Thoracic Aortic Aneurysms and Acute Aortic Dissections.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Local variations in material and structural properties characterize murine thoracic aortic aneurysm mechanics.Biomechanics and modeling in mechanobiology · 2019Article
- Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation.Cardiovascular research · 2018Article
- Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans.Circulation research · 2018Article
- ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice.Clinics (Sao Paulo, Brazil) · 2018Article
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Aortic aneurysms are life-threatening and often associated with defects in connective tissues and mutations in smooth muscle cell (SMC) contractile proteins. Despite recent advances in understanding altered signaling in aneurysms of Marfan syndrome, the underlying mechanisms and options for pharmacological treatment for other forms of aneurysms are still under investigation. We previously showed in mice that deficiency in the fibulin-4 gene in vascular SMCs (Fbln4(SMKO)) leads to loss of the SMC contractile phenotype, hyperproliferation, and ascending aortic aneurysms. We report that abnormal up-regulation of angiotensin-converting enzyme (ACE) in SMCs and subsequent activation of angiotensin II (AngII) signaling are involved in the onset of aortic aneurysms in Fbln4(SMKO) mice. In this model, aneurysm formation was completely prevented by inhibition of the AngII pathway with losartan or captopril within a narrow therapeutic window during the first month of life, even though the altered mechanical properties of blood vessel walls were not reversed by the pharmacological treatment. The therapeutic effects of losartan in Fbln4(SMKO) mice do not require the AngII receptor type 2 (Agtr2) but likely require both type 1a (Agtr1a) and 1b (Agtr1b) receptors. The results indicate that fibulin-4 is a vascular matrix component required for regulation of local angiotensin signaling and development and maintenance of the SMC phenotype.
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