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| Open AccessAGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling
Thoracic aortic aneurysm (TAA) causes many sudden deaths each year, however, no effective drug treatment is available. Here, the authors show that AGGF1 protein therapy attenuates TAA in three different mouse models through integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signalling.
- Xingwen Da
- , Ziyan Li
- & Qing K. Wang
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Article
| Open AccessGenome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic variants linked to aortic distensibility, highlighting mechanistic pathways and causal relationships between distensibility and both aortic aneurysms and brain small vessel disease.
- Catherine M. Francis
- , Matthias E. Futschik
- & Paul M. Matthews
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| Open AccessMicroskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1
Mechanobiological signals have been reported to contribute to abdominal aortic aneurysm (AAA) development. Here the authors report that the microskeletal stiffness and a Piezo1-mediated mechanism influence vascular smooth muscle cell mechanosensation and AAA disease development.
- Weiyi Qian
- , Tarik Hadi
- & Weiqiang Chen
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Article
| Open AccessAortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO
Aortic aneurysm and dissection, the major problem linked to Marfan syndrome (MFS), lacks effective pharmacological treatment. Here, the authors show that the NO pathway is overactivated in MFS and that inhibition of guanylate cyclase and cGMP-dependent protein kinase reverts MFS aortopathy in mice.
- Andrea de la Fuente-Alonso
- , Marta Toral
- & Juan Miguel Redondo
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Article
| Open AccessIL-27 receptor-regulated stress myelopoiesis drives abdominal aortic aneurysm development
Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression
- Iuliia O. Peshkova
- , Turan Aghayev
- & Ekaterina K. Koltsova
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Article
| Open AccessAortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B12 analog
Individuals carrying a gain-of-function mutation in PKG1 develop thoracic aortic aneurysms and dissections. Here Schwaerzer et al. show that mice carrying the same mutation recapitulate the human disease, and find that treatment with anti-oxidants including cobinamide, a vitamin B12 analog, prevents disease progression.
- Gerburg K. Schwaerzer
- , Hema Kalyanaraman
- & Renate B. Pilz
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Article
| Open AccessMacrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells
Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix degradation. Here Hadi et al. identify a netrin-1/neogenin-based crosstalk between macrophages and vascular smooth muscle cells (VSMCs), leading to the secretion of the matrix metalloproteinase MMP-3 by VSMCs and subsequent matrix degradation in AAA lesions.
- Tarik Hadi
- , Ludovic Boytard
- & Bhama Ramkhelawon
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Article
| Open AccessAn HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Vascular smooth muscle cell (VSMC) dysfunction is a common feature of thoracic aortic aneurysms (TAAs). Here, Lino Cardenas and colleagues show that the formation of a HDAC9-MALAT1-BRG1 complex promotes VSMC dysfunction in TAA by epigenetically altering the expression of key components of the cytoskeleton in VSMCs.
- Christian L. Lino Cardenas
- , Chase W. Kessinger
- & Mark E. Lindsay
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Article
| Open AccessHomocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury
High homocysteine plasma levels are associated with cardiovascular diseases. Here, Li and colleagues find that homocysteine aggravates vascular injury by direct binding to the angiotensin II type 1 receptor (AT1R), identifying AT1R inhibition as a potential strategy to counteract the deleterious vascular effects of hyperhomocysteinemia.
- Tuoyi Li
- , Bing Yu
- & Wei Kong
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Article
| Open AccessRGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
Vascular inflammation plays a key role in pathogenesis of major vascular diseases. Here the authors show that Regulator of G-Protein Signaling-1 (RGS1) controls macrophage function in the development of vascular inflammation that underlies atherosclerosis and abdominal aortic aneurysms in mice and humans.
- Jyoti Patel
- , Eileen McNeill
- & Keith M. Channon
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Article
| Open AccessmiR-24 limits aortic vascular inflammation and murine abdominal aneurysm development
Abdominal aortic aneurysm (AAA) is a potentially fatal and often asymptomatic disease whose causes remain unclear. Here the authors show that a microRNA, miR-24, and its target, the glycoprotein chitinase 3-like 1, represent key regulators of AAA development.
- Lars Maegdefessel
- , Joshua M. Spin
- & Philip S. Tsao