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Vascular biology

  • 230 Articles
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Deficiency of cathepsin S reduces atherosclerosis in LDL receptor–deficient mice
Galina K. Sukhova, … , Peter Libby, Guo-Ping Shi
Galina K. Sukhova, … , Peter Libby, Guo-Ping Shi
Published March 15, 2003
Citation Information: J Clin Invest. 2003;111(6):897-906. https://doi.org/10.1172/JCI14915.
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Deficiency of cathepsin S reduces atherosclerosis in LDL receptor–deficient mice

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Abstract

Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known. In contrast, atheromata have low levels of the endogenous Cat S inhibitor cystatin C compared with normal arteries, suggesting involvement of this protease in atherogenesis. The present study tested this hypothesis directly by crossing Cat S–deficient (CatS–/–) mice with LDL receptor–deficient (LDLR–/–) mice that develop atherosclerosis on a high-cholesterol diet. Compared with LDLR–/– mice, double-knockout mice (CatS–/–LDLR–/–) developed significantly less atherosclerosis, as indicated by plaque size (plaque area and intimal thickening) and stage of development. These mice also had markedly reduced content of intimal macrophages, lipids, smooth muscle cells, collagen, CD4+ T lymphocytes, and levels of IFN-γ. CatS–/–LDLR–/– monocytes showed impaired subendothelial basement membrane transmigration, and aortas from CatS–/–LDLR–/– mice had preserved elastic laminae. These findings establish a pivotal role for Cat S in atherogenesis.

Authors

Galina K. Sukhova, Yaou Zhang, Jie-Hong Pan, Youichiro Wada, Takashi Yamamoto, Makoto Naito, Tatsuhiko Kodama, Sotirios Tsimikas, Joseph L. Witztum, Michael L. Lu, Yasuhiko Sakara, Michael T. Chin, Peter Libby, Guo-Ping Shi

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Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):333-340. https://doi.org/10.1172/JCI15555.
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Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis

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Abstract

The hallmark of early atherosclerosis is the accumulation of lipid-laden macrophages in the subendothelial space. Circulating monocytes are the precursors of these “foam cells,” and recent evidence suggests that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes. A polymorphism in the FK receptor, CX3CR1, has been linked to a decrease in the incidence of coronary artery disease. To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX3CR1 and crossed these mice into the apoE–/– background. Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE–/– mice on a high-fat diet. CX3CR1–/– mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis.

Authors

Philippe Lesnik, Christopher A. Haskell, Israel F. Charo

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A novel form of integrin dysfunction involving β1, β2, and β3 integrins
Alison McDowall, … , Nigel Klein, Nancy Hogg
Alison McDowall, … , Nigel Klein, Nancy Hogg
Published January 1, 2003
Citation Information: J Clin Invest. 2003;111(1):51-60. https://doi.org/10.1172/JCI14076.
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A novel form of integrin dysfunction involving β1, β2, and β3 integrins

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Abstract

The adhesion receptors known as integrins perform key functions for hematopoietic cells. The platelet integrin αIIbβ3 is critical in hemostasis, and the β1 and β2 integrins on leukocytes have many roles in cell-mediated immunity. Mutations in the β2 subunit lead to integrin nonexpression and to an immune deficiency, leukocyte adhesion deficiency-1. Mutations in either the α or β subunit of αIIbβ3 usually lead to integrin nonexpression and a bleeding tendency termed Glanzmann thrombasthenia. Here we describe a unique patient with clinical features of both Glanzmann thrombasthenia and leukocyte adhesion deficiency-1. The patient has normal expression of β1, β2, and β3 integrins, but all are dysfunctional. The key findings are that “inside-out” signaling pathways leading to integrin activation are defective and that this is associated with abnormal integrin clustering. The integrins themselves are intact and capable of function following extracellular stimulation. T cell motility is normal, as are the expression levels and electrophoretic characteristics of all cytoskeletal and signaling proteins tested, except PKC-α, which has enhanced expression in the patient’s cells. To our knowledge, this is the first description of a dysfunction affecting three classes of integrins. We propose that it is caused by a lesion in an intracellular factor or signaling pathway essential for integrin activation in hematopoietic cells and results in lack of regulation of clustering, an essential component of integrin-mediated adhesion.

Authors

Alison McDowall, David Inwald, Birgit Leitinger, Alison Jones, Ri Liesner, Nigel Klein, Nancy Hogg

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Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids
Florian P. Limbourg, … , Michael A. Moskowitz, James K. Liao
Florian P. Limbourg, … , Michael A. Moskowitz, James K. Liao
Published December 1, 2002
Citation Information: J Clin Invest. 2002;110(11):1729-1738. https://doi.org/10.1172/JCI15481.
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Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids

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Abstract

Research Article

Authors

Florian P. Limbourg, Zhihong Huang, Jean-Christophe Plumier, Tommaso Simoncini, Masayuki Fujioka, Jan Tuckermann, Günther Schütz, Michael A. Moskowitz, James K. Liao

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In vivo regulation of plasminogen function by plasma carboxypeptidase B
Carmen M. Swaisgood, … , Dan Eaton, Edward F. Plow
Carmen M. Swaisgood, … , Dan Eaton, Edward F. Plow
Published November 1, 2002
Citation Information: J Clin Invest. 2002;110(9):1275-1282. https://doi.org/10.1172/JCI15082.
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In vivo regulation of plasminogen function by plasma carboxypeptidase B

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Abstract

Research Article

Authors

Carmen M. Swaisgood, Detlef Schmitt, Dan Eaton, Edward F. Plow

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Inhibition of endothelial cell survival and angiogenesis by protein kinase A
Semi Kim, … , Hong Yin, Judith A. Varner
Semi Kim, … , Hong Yin, Judith A. Varner
Published October 1, 2002
Citation Information: J Clin Invest. 2002;110(7):933-941. https://doi.org/10.1172/JCI14268.
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Inhibition of endothelial cell survival and angiogenesis by protein kinase A

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Abstract

Research Article

Authors

Semi Kim, Manjiri Bakre, Hong Yin, Judith A. Varner

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Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms
G. Matthew Longo, … , Nicola Fiotti, B. Timothy Baxter
G. Matthew Longo, … , Nicola Fiotti, B. Timothy Baxter
Published September 1, 2002
Citation Information: J Clin Invest. 2002;110(5):625-632. https://doi.org/10.1172/JCI15334.
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Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms

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Abstract

Research Article

Authors

G. Matthew Longo, Wanfen Xiong, Timothy C. Greiner, Yong Zhao, Nicola Fiotti, B. Timothy Baxter

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Different mechanisms underlying the stimulation of KCa channels by nitric oxide and carbon monoxide
Lingyun Wu, … , Yanjie Lu, Rui Wang
Lingyun Wu, … , Yanjie Lu, Rui Wang
Published September 1, 2002
Citation Information: J Clin Invest. 2002;110(5):691-700. https://doi.org/10.1172/JCI15316.
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Different mechanisms underlying the stimulation of KCa channels by nitric oxide and carbon monoxide

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Abstract

Research Article

Authors

Lingyun Wu, Kun Cao, Yanjie Lu, Rui Wang

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A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors
Christopher Heeschen, … , Stefanie Dimmeler, John P. Cooke
Christopher Heeschen, … , Stefanie Dimmeler, John P. Cooke
Published August 15, 2002
Citation Information: J Clin Invest. 2002;110(4):527-536. https://doi.org/10.1172/JCI14676.
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A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors

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Abstract

Research Article

Authors

Christopher Heeschen, Michael Weis, Alexandra Aicher, Stefanie Dimmeler, John P. Cooke

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Cyclooxygenase-1–selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus
Charles D. Loftin, … , Darshini B. Trivedi, Robert Langenbach
Charles D. Loftin, … , Darshini B. Trivedi, Robert Langenbach
Published August 15, 2002
Citation Information: J Clin Invest. 2002;110(4):549-557. https://doi.org/10.1172/JCI14924.
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Cyclooxygenase-1–selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus

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Abstract

Research Article

Authors

Charles D. Loftin, Darshini B. Trivedi, Robert Langenbach

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MiR-33 fine-tunes atherosclerotic plaque inflammation
Mireille Ouimet, Hasini Ediriweera, and colleagues show that miR-33 controls the macrophage inflammatory program and promotes atherosclerotic plaque development…
Published October 26, 2015
Scientific Show StopperVascular biology

Contracting lacteals send lipids down the drain
Kibaek Choe, Jeon Yeob Jang, Intae Park and colleagues visualize lipid drainage through lacteals using intravital, video-rate microscopy…
Published October 5, 2015
Scientific Show StopperVascular biology

FOXC2 keeps lymphatic vessels leak-proof
Amélie Sabine and colleagues demonstrate that disturbed flow in lymphatic vasculature induces expression of the transcription factor FOXC2, which is essential for maintaining normal endothelial cell morphology and vessel integrity…
Published September 21, 2015
Scientific Show StopperVascular biology

Venous malformation model provides therapeutic insight
Elisa Boscolo and colleagues develop a murine model of venous malformation and demonstrate that rapamycin improves clinical symptoms of in this model and in patients…
Published August 10, 2015
Scientific Show StopperVascular biology

Lymphatic valves grow with the flow
Daniel Sweet and colleagues reveal that lymph flow is essential for lymphatic vessel maturation…
Published July 27, 2015
Scientific Show StopperVascular biology

GATA2 serves as a lymphatic rheostat
Jan Kazenwadel, Kelly Betterman, and colleagues reveal that the transcription factor GATA2 is essential for lymphatic valve development and maintenance…
Published July 27, 2015
Scientific Show StopperVascular biology

Factoring in factor XII in hereditary angioedema III
Jenny Björkqvist and colleagues elucidate the mechanism by which hereditary angioedema III-associated factor XII promotes vascular leakage…
Published July 20, 2015
Scientific Show StopperVascular biology

Regional regulation of atherosclerosis
Yogendra Kanthi, Matthew Hyman, and colleagues reveal that CD39 is regulated by blood flow and is protective against atherosclerosis…
Published June 29, 2015
Scientific Show StopperVascular biology
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