Abstract:
:We describe a straightforward gene-targeting technique to achieve uniform, stable, and genetically invariant expression of a transgene in the vascular endothelium of mice. To demonstrate the feasibility of this approach, the reporter gene bacterial beta-galactosidase was inserted via homologous recombination into the intronless thrombomodulin locus of murine embryonic stem cells. In this fashion, the lacZ gene is placed under the regulatory control of the endogenous thrombomodulin promoter. The expression of the transgene in adult mice recapitulated the widespread, stable, and high-level expression of the thrombomodulin gene in vascular endothelium. These data indicate that targeting of cDNAs into the thrombomodulin locus serves as a viable strategy to express transgenes in endothelial cells. Analysis of reporter gene expression revealed a heterogeneous pattern of thrombomodulin gene activity in the endothelium of the aorta and its tributaries. We also show that embryonic stem cells with a targeted thrombomodulin locus contribute in a mosaic fashion to the vascular endothelium of chimeric mice. This method for generating animals with a functionally heterogeneous cardiovascular system should provide an experimental technique for studying how localized genetic abnormalities in endothelial cell function lead to the development of vascular diseases.
journal_name
Circ Resjournal_title
Circulation researchauthors
Weiler-Guettler H,Aird WC,Husain M,Rayburn H,Rosenberg RDdoi
10.1161/01.res.78.2.180subject
Has Abstractpub_date
1996-02-01 00:00:00pages
180-7issue
2eissn
0009-7330issn
1524-4571journal_volume
78pub_type
杂志文章abstract::The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.460
更新日期:1992-08-01 00:00:00
abstract:RATIONALE:We previously discovered several phosphorylations to the beta subunit of the mitochondrial F(1)F(o) ATP synthase complex in isolated rabbit myocytes on adenosine treatment, an agent that induces cardioprotection. The role of these phosphorylations is unknown. OBJECTIVE:The present study focuses on the functi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.214155
更新日期:2010-02-19 00:00:00
abstract:RATIONALE:Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. OBJECTIVE:To identify and characterize artery- an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316075
更新日期:2020-03-27 00:00:00
abstract::Ventricular muscle fibers from dog hearts were superfused with K+-free, high Ca2+ solutions after exposure to a K+-free, Ca2+-free superfusate. Following a series of driven action potentials, oscillatory after potentials (OAPs) were elicited in all 40 preparations at a resting potential of greater than -60 mV. The OAP...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.4.510
更新日期:1981-04-01 00:00:00
abstract::Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor tr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2001.097691
更新日期:2001-10-12 00:00:00
abstract:RATIONALE:Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE:To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS:We enrolled 214 children...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305834
更新日期:2015-02-27 00:00:00
abstract::Recent evidence suggests that dopamine may alter kidney function by actions not only in the renal vasculature but also at the glomerular-mesangial level. We studied this phenomenon by examining the ability of dopamine to antagonize the contractile properties of angiotensin II in isolated rat glomeruli and cultured mes...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.59.5.529
更新日期:1986-11-01 00:00:00
abstract::During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isome...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.1.127
更新日期:1995-01-01 00:00:00
abstract:RATIONALE:Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE:We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.312821
更新日期:2018-05-25 00:00:00
abstract::Effects of concentrations of intracellular calcium, [Ca2+]i, on the voltage-dependent Ca2+ current (ICa) recorded from dispersed single smooth muscle cells of the rabbit portal vein were studied, using a whole cell voltage clamp method combined with an intracellular perfusion technique. Outward currents were minimized...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.375
更新日期:1988-02-01 00:00:00
abstract:RATIONALE:Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs). OBJECTIVE:To determine whether a PPARγ agonist reduces angiotensin II (Ang II)-induced ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.219089
更新日期:2010-10-15 00:00:00
abstract::The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.155
更新日期:1988-01-01 00:00:00
abstract::Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1, one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show h...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000173047.42236.88
更新日期:2005-07-08 00:00:00
abstract::Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise,...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.303505
更新日期:2015-04-24 00:00:00
abstract::The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.6.864
更新日期:1985-12-01 00:00:00
abstract::Long QT syndrome (LQTS) type 3 (LQT3), typified by the DeltaKPQ mutation (LQT3 mutation in which amino acid residues 1505 to 1507 [KPQ] are deleted), is caused by increased sodium entry during the action potential plateau resulting from mutation-altered inactivation of the Na(v)1.5 channel. Although rare, LQT3 is the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000251305.25604.b0
更新日期:2006-11-24 00:00:00
abstract::We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.2.530
更新日期:1991-08-01 00:00:00
abstract::Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.234
更新日期:1992-02-01 00:00:00
abstract:RATIONALE:Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE:The purpose of ...
journal_title:Circulation research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCRESAHA.116.304710
更新日期:2015-01-02 00:00:00
abstract:RATIONALE:Congestive heart failure (CHF) frequently results in remodeling and increased tone of pulmonary resistance vessels. This adaptive response, which aggravates pulmonary hypertension and thus, promotes right ventricular failure, has been attributed to lung endothelial dysfunction. OBJECTIVE:We applied real-time...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.210542
更新日期:2010-04-02 00:00:00
abstract::The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.606
更新日期:1985-04-01 00:00:00
abstract::Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.304678
更新日期:2015-06-05 00:00:00
abstract::Isolated adult rat hearts perfused in an isovolumic mode were used to study the effects of sodium-potassium pump inhibition and sodium-calcium exchange alterations on the tissue content of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH, all measured by phosphorus-31 nuclear magnetic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.539
更新日期:1986-04-01 00:00:00
abstract::14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000104084.88317.91
更新日期:2003-11-28 00:00:00
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
更新日期:2020-10-23 00:00:00
abstract:RATIONALE:Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein that is expressed in mammalian myocardium under normal conditions and upregulated in pathological states such as heart failure. UCP2 is thought to protect cardiomyocytes against oxidative stress by dissipating the mitochondrial proton gradien...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206631
更新日期:2010-03-05 00:00:00
abstract::Originally identified as moderate biological modifiers, microRNAs have recently emerged as powerful regulators of diverse cellular processes with especially important roles in disease and tissue remodeling. The rapid pace of studies on microRNA regulation and function necessitates the development of suitable technique...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.227496
更新日期:2011-01-21 00:00:00
abstract::The dystrophin glycoprotein complex (DGC) is a specialization of cardiac and skeletal muscle membrane. This large multicomponent complex has both mechanical stabilizing and signaling roles in mediating interactions between the cytoskeleton, membrane, and extracellular matrix. Dystrophin, the protein product of the Duc...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000126574.61061.25
更新日期:2004-04-30 00:00:00
abstract::Vascular disease often involves vessel hypertrophy with underlying cellular hypertrophy or hyperplasia. Experimental diabetes stimulates hypertrophy of the rat mesenteric vasculature, and we investigated the hypothesis that this hypertrophy is associated with activation of Na(+)-H(+) exchange (NHE) activity. We measur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.12.1133
更新日期:2000-12-08 00:00:00
abstract::Disorders of L-type Ca2+ channels can cause severe cardiac arrhythmias. A subclass of small GTP-binding proteins, the RGK family, regulates L-type Ca2+ current (I(Ca,L)) in heterologous expression systems. Among these proteins, Rad (Ras associated with diabetes) is highly expressed in the heart, although its role in t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.106.146399
更新日期:2007-07-06 00:00:00