Urokinase-type plasminogen activator plays a critical role in angiotensin II-induced abdominal aortic aneurysm.

Abstract:

:We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA formation in this model. An osmotic minipump containing Ang II (1.44 mg/kg per day) was implanted subcutaneously into 7- to 11-month-old male mice for 1 month. Ang II induced AAA in 9 (90%) of 10 hyperlipidemic mice deficient in apoE (apoE-/-/uPA+/+ mice) but in only 2 (22%) of 9 mice deficient in both apoE and uPA (apoE-/-/uPA-/- mice) (P<0.05). Although the expansion of the suprarenal aorta was significantly less in apoE-/-/uPA-/- mice than in apoE-/-/uPA+/+ mice, the aortic diameters of the aorta immediately above or below the suprarenal aorta were similar between the 2 groups. Ang II induced AAA in 7 (39%) of 18 strain-matched wild-type C57 black/6J control mice. The incidence was significantly higher in atherosclerotic apoE-deficient (apoE-/-) mice, in which 8 (100%) of 8 mice developed AAA. Only 1 (4%) of 27 uPA-/- mice developed AAA after Ang II treatment. We conclude the following: (1) uPA plays an essential role in Ang II-induced AAA in mice with or without preexisting hyperlipidemia and atherosclerosis; (2) uPA deficiency does not affect the diameter of the nonaneurysmal portion of the aorta; and (3) atherosclerosis and/or hyperlipidemia promotes but is not essential for Ang II-induced AAA formation in this model.

journal_name

Circ Res

journal_title

Circulation research

authors

Deng GG,Martin-McNulty B,Sukovich DA,Freay A,Halks-Miller M,Thinnes T,Loskutoff DJ,Carmeliet P,Dole WP,Wang YX

doi

10.1161/01.RES.0000061571.49375.E1

subject

Has Abstract

pub_date

2003-03-21 00:00:00

pages

510-7

issue

5

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000061571.49375.E1

journal_volume

92

pub_type

杂志文章
  • Intermittent hypoxia in rats increases myogenic tone through loss of hydrogen sulfide activation of large-conductance Ca(2+)-activated potassium channels.

    abstract:RATIONALE:Myogenic tone, an important regulator of vascular resistance, is dependent on vascular smooth muscle (VSM) depolarization, can be modulated by endothelial factors, and is increased in several models of hypertension. Intermittent hypoxia (IH) elevates blood pressure and causes endothelial dysfunction. Hydrogen...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.228999

    authors: Jackson-Weaver O,Paredes DA,Gonzalez Bosc LV,Walker BR,Kanagy NL

    更新日期:2011-06-10 00:00:00

  • Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response.

    abstract::Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and func...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000200162.94463.d7

    authors: Tzima E

    更新日期:2006-02-03 00:00:00

  • The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes.

    abstract::Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling pathways was undertaken in primary cultures of cardiac myocytes, a cell type that is especially sensitive to...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.85.5.403

    authors: Bialik S,Cryns VL,Drincic A,Miyata S,Wollowick AL,Srinivasan A,Kitsis RN

    更新日期:1999-09-03 00:00:00

  • Elevations in arterial pressure induce the formation of spontaneous action potentials and alter neurotransmission in canine ileum arteries.

    abstract::Arterial segments (less than 250 micron o.d.) excised from canine ileum were mounted in a chamber that permitted arterial transmural pressure (TMP) to be altered and measured. Subsequently, the periarterial nerves were field stimulated with single pulses (0.1 msec, 70 V), and the resting membrane potential (Em) as wel...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.6.1104

    authors: Smeda JS,Daniel EE

    更新日期:1988-06-01 00:00:00

  • Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.

    abstract::-ATP-sensitive potassium (K(ATP)) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K(ATP) channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K(ATP) channels...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.88.6.570

    authors: Suzuki M,Li RA,Miki T,Uemura H,Sakamoto N,Ohmoto-Sekine Y,Tamagawa M,Ogura T,Seino S,Marbán E,Nakaya H

    更新日期:2001-03-30 00:00:00

  • Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes.

    abstract:RATIONALE:Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region. OBJECTIVE:To establish the association of P...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.201418

    authors: Sato PY,Musa H,Coombs W,Guerrero-Serna G,Patiño GA,Taffet SM,Isom LL,Delmar M

    更新日期:2009-09-11 00:00:00

  • Oxidative posttranslational modifications mediate decreased SERCA activity and myocyte dysfunction in Galphaq-overexpressing mice.

    abstract:BACKGROUND:Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation. OBJE...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.217570

    authors: Lancel S,Qin F,Lennon SL,Zhang J,Tong X,Mazzini MJ,Kang YJ,Siwik DA,Cohen RA,Colucci WS

    更新日期:2010-07-23 00:00:00

  • Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart.

    abstract::We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuro...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.1.137

    authors: Yang T,Levy MN

    更新日期:1993-01-01 00:00:00

  • Rapid attenuation ("fade") of the chronotropic response during vagal stimulation in the canine newborn. Evidence for a prominent neuropeptide Y effect.

    abstract::We studied the time-dependent changes in the response of heart rate (sinus cycle length) to 30-second trains of vagal stimulation (8 Hz), repeated every 2 minutes, in canine neonates aged 7.1 +/- 2.5 (mean +/- SD) days. The first vagal train prolonged the sinus cycle length by 58 +/- 35%, but the response was attenuat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.2.406

    authors: Yamasaki S,Stolfi A,Mas MS,Fox LS,Pickoff AS

    更新日期:1991-08-01 00:00:00

  • High-Density Lipoprotein Carries Markers That Track With Recovery From Stroke.

    abstract:RATIONALE:Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. OBJECTIVE:Investigate the relationship between long-term functional recovery and HDL proteome and function. METHODS AND RESULTS:Changes in HDL protein composition and function (cholester...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.316526

    authors: Plubell DL,Fenton AM,Rosario S,Bergstrom P,Wilmarth PA,Clark WM,Zakai NA,Quinn JF,Minnier J,Alkayed NJ,Fazio S,Pamir N

    更新日期:2020-10-23 00:00:00

  • Innate and adaptive immunity in the pathogenesis of atherosclerosis.

    abstract::This review considers critically the evidence for the involvement of mediators of innate and acquired immunity in various stages of atherosclerosis. Rapidly mobilized arms of innate immunity, including phagocytic leukocytes, complement, and proinflammatory cytokines, contribute to atherogenesis. In addition, adaptive ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.0000029784.15893.10

    authors: Hansson GK,Libby P,Schönbeck U,Yan ZQ

    更新日期:2002-08-23 00:00:00

  • A solid angle analysis of the epicardial ischemic TQ-ST deflection in the pig. A theoretical and experimental study.

    abstract::The solid angle theory has long been applied to the interpretation of the ECG; however, quantitative evaluation of its applicability has been minimal. We applied solid angle analysis to the interpretation of the TQ-ST deflection during acute ischemia. Five anesthetized pigs were studied 1--3 hours after coronary occlu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.43.6.879

    authors: Richeson JF,Akiyama T,Schenk E

    更新日期:1978-12-01 00:00:00

  • Evidence for isoproterenol-induced phosphorylation of phosphatase inhibitor-1 in the intact heart.

    abstract::The positive inotropic effect of the beta-adrenoceptor agonist isoproterenol is accompanied by inhibition of phosphatase type 1 activity in myocardium. Indirect assays suggest that this effect is due to activation of protein phosphatase inhibitor-1, which inhibits phosphatase activity only when phosphorylated. To test...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.6.1450

    authors: Neumann J,Gupta RC,Schmitz W,Scholz H,Nairn AC,Watanabe AM

    更新日期:1991-12-01 00:00:00

  • Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

    abstract::We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.45.3.404

    authors: Hyman AL,Kadowitz PJ

    更新日期:1979-09-01 00:00:00

  • An osteopontin-NADPH oxidase signaling cascade promotes pro-matrix metalloproteinase 9 activation in aortic mesenchymal cells.

    abstract::Osteopontin (OPN) is a cytokine upregulated in diabetic vascular disease. To better understand its role in vascular remodeling, we assessed how OPN controls metalloproteinase (MMP) activation in aortic adventitial myofibroblasts (AMFs) and A7r5 vascular smooth muscle cells (VSMCs). By zymography, OPN and tumor necrosi...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000227550.00426.60

    authors: Lai CF,Seshadri V,Huang K,Shao JS,Cai J,Vattikuti R,Schumacher A,Loewy AP,Denhardt DT,Rittling SR,Towler DA

    更新日期:2006-06-23 00:00:00

  • Role for tissue factor pathway in murine model of vascular remodeling.

    abstract::Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1301.092508

    authors: Singh R,Pan S,Mueske CS,Witt T,Kleppe LS,Peterson TE,Slobodova A,Chang JY,Caplice NM,Simari RD

    更新日期:2001-07-06 00:00:00

  • Effects of intracellular angiotensin II in vascular smooth muscle cells.

    abstract::Angiotensin (Ang) II is present inside vascular smooth muscle cells (VSMCs); however, its intracellular functions, if any, are unknown. We tested the hypothesis that intracellular Ang II exerts effects on cytosolic Ca2+ ([Ca2+]i) in VSMCs. Ang II was administered via microinjection. Intracellular Ang II localization w...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.79.4.765

    authors: Haller H,Lindschau C,Erdmann B,Quass P,Luft FC

    更新日期:1996-10-01 00:00:00

  • Molecular and particulate depositions for regional myocardial flows in sheep.

    abstract::The deposition of microspheres in small tissue regions is not strictly flow dependent. In comparison with the soluble flow marker 2-iododesmethylimipramine (IDMI), deposition of 16.5-microns microspheres was mildly but systematically biased into high flow regions of rabbit hearts (Bassingthwaighte JB, Malone MA, Moffe...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.5.1328

    authors: Bassingthwaighte JB,Malone MA,Moffett TC,King RB,Chan IS,Link JM,Krohn KA

    更新日期:1990-05-01 00:00:00

  • A Path Forward for Regenerative Medicine.

    abstract::Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval and identify strategies to facilitate this goal, the Cardiac S...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.118.313261

    authors: Fanaroff AC,Morrow V,Krucoff MW,Seltzer JH,Perin EC,Taylor DA,Miller LW,Zeiher AM,Fernández-Avilés F,Losordo DW,Henry TD,Povsic TJ

    更新日期:2018-08-03 00:00:00

  • Live Imaging of Intracranial Lymphatics in the Zebrafish.

    abstract:RATIONALE:The recent discovery of meningeal lymphatics in mammals is reshaping our understanding of fluid homeostasis and cellular waste management in the brain, but visualization and experimental analysis of these vessels is challenging in mammals. Although the optical clarity and experimental advantages of zebrafish ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317372

    authors: Castranova D,Samasa B,Venero Galanternik M,Jung HM,Pham VN,Weinstein BM

    更新日期:2021-01-08 00:00:00

  • A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

    abstract:RATIONALE:Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) receptors may have divergent effects on target organ damage in hyper...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.261768

    authors: Zhang JD,Patel MB,Song YS,Griffiths R,Burchette J,Ruiz P,Sparks MA,Yan M,Howell DN,Gomez JA,Spurney RF,Coffman TM,Crowley SD

    更新日期:2012-06-08 00:00:00

  • Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells.

    abstract::We examined the role of endogenous NO in the autonomic regulation of atrioventricular (AV) nodal function by studying spontaneous action potentials (SAPs) and L-type Ca2+ current (ICa-L) in isolated single AV nodal cells from adult rabbit hearts. Both the perforated and the membrane-ruptured patch-clamp techniques in ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.78.6.998

    authors: Han X,Kobzik L,Balligand JL,Kelly RA,Smith TW

    更新日期:1996-06-01 00:00:00

  • L-type Ca2+ channel density and regulation are altered in failing human ventricular myocytes and recover after support with mechanical assist devices.

    abstract::Ca2+ influx through the L-type calcium channel (LTCC) induces Ca2+ release from the sarcoplasmic reticulum (SR) and maintains SR Ca2+ loading. Alterations in LTCC properties, their contribution to the blunted adrenergic responsiveness in failing hearts and their recovery after support with LV assist devices (LVAD) wer...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000033988.13062.7c

    authors: Chen X,Piacentino V 3rd,Furukawa S,Goldman B,Margulies KB,Houser SR

    更新日期:2002-09-20 00:00:00

  • Protein kinase C activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes.

    abstract::The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.5.412

    authors: Yuan SY,Ustinova EE,Wu MH,Tinsley JH,Xu W,Korompai FL,Taulman AC

    更新日期:2000-09-01 00:00:00

  • Modulation of cerebral arteriolar diameter by intraluminal flow and pressure.

    abstract::We determined whether cerebral arterioles in vitro adjust their diameters in response to changes in intraluminal flow rate and pressure. Intracerebral arterioles (38- to 55-microns diameter) were isolated from Sprague-Dawley rats and cannulated with a perfusion system that permitted separate control of intraluminal pr...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.77.4.832

    authors: Ngai AC,Winn HR

    更新日期:1995-10-01 00:00:00

  • Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.

    abstract::The signaling pathways involved in the long-term metabolic effects of angiotensin II (Ang II) in vascular smooth muscle cells are incompletely understood but include the generation of molecules likely to affect oxidase activity. We examined the ability of Ang II to stimulate superoxide anion formation and investigated...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.6.1141

    authors: Griendling KK,Minieri CA,Ollerenshaw JD,Alexander RW

    更新日期:1994-06-01 00:00:00

  • Role of the mitochondrial permeability transition in myocardial disease.

    abstract::Mitochondria play a key role in determining cell fate during exposure to stress. Their role during ischemia/reperfusion is particularly critical because of the conditions that promote both apoptosis by the mitochondrial pathway and necrosis by irreversible damage to mitochondria in association with mitochondrial perme...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000087542.26971.D4

    authors: Weiss JN,Korge P,Honda HM,Ping P

    更新日期:2003-08-22 00:00:00

  • Unspliced XBP1 Confers VSMC Homeostasis and Prevents Aortic Aneurysm Formation via FoxO4 Interaction.

    abstract:RATIONALE:Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs) may confer vascular hom...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.311450

    authors: Zhao G,Fu Y,Cai Z,Yu F,Gong Z,Dai R,Hu Y,Zeng L,Xu Q,Kong W

    更新日期:2017-12-08 00:00:00

  • Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling.

    abstract:RATIONALE:Transcatheter, intramyocardial injections of bone marrow-derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. OBJECTIVE:We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothes...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.242610

    authors: Williams AR,Trachtenberg B,Velazquez DL,McNiece I,Altman P,Rouy D,Mendizabal AM,Pattany PM,Lopera GA,Fishman J,Zambrano JP,Heldman AW,Hare JM

    更新日期:2011-04-01 00:00:00

  • Contractile failure and high-energy phosphate turnover during hypoxia: 31P-NMR surface coil studies in living rat.

    abstract::Cardiac failure appears rapidly during severe hypoxia and precedes a substantial reduction in adenosine triphosphate content. Reduced adenosine triphosphate turnover, in the presence of nearly normal content, may be the metabolic basis for contractile failure during hypoxia. To measure both the myocardial content and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.60.6.871

    authors: Bittl JA,Balschi JA,Ingwall JS

    更新日期:1987-06-01 00:00:00