Abstract:
:Nonlaminar flow is a major predisposing factor to atherosclerosis. Yet little is known regarding hemodynamic gene regulation in disease-prone areas of the vascular tree in vivo. We have determined spatial patterns of expression of endothelial cell receptors in the arterial tree and of reporter gene constructs in transgenic animals. In this study we show that the endothelial cell-specific receptor Tie1 is induced by disturbed flow in atherogenic vascular niches. Specifically, tie1 expression in the adult is upregulated in vascular bifurcations and branching points along the arterial tree. It is often confined to a single ring of endothelial cells functioning as sphincters and hence experiencing the steepest gradient in shear stress. In aortic valves, tie1 is asymmetrically induced only in endothelial cells encountering changes in flow direction. Disturbance of laminar flow by a surgical interposition of a vein into an artery led to induction of tie1, specifically in the region where the differently sized vessels adjoin. In pathological settings, tie1 expression is specifically induced in areas of disturbed flow because of the emergence of aneurysms and, importantly, in endothelial cells precisely overlying atherosclerotic plaques. Hemodynamic features of atherosclerotic lesion-prone regions, recreated in vitro with the aid of a flow chamber with a built-in step, corroborated an upregulated tie1 promoter activity only in cells residing where flow separation and recirculation take place. These defined promoter elements might be harnessed for targeting gene expression to atherosclerotic lesions.
journal_name
Circ Resjournal_title
Circulation researchauthors
Porat RM,Grunewald M,Globerman A,Itin A,Barshtein G,Alhonen L,Alitalo K,Keshet Edoi
10.1161/01.RES.0000111803.92923.D6subject
Has Abstractpub_date
2004-02-20 00:00:00pages
394-401issue
3eissn
0009-7330issn
1524-4571pii
01.RES.0000111803.92923.D6journal_volume
94pub_type
杂志文章abstract::Smooth muscle cell migration in response to platelet-derived growth factor (PDGF) is a key event in several vascular pathologies, including atherosclerosis and restenosis. PDGF increases intracellular levels of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs), but the ROS sensitivity of migration ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000126848.54740.4A
更新日期:2004-05-14 00:00:00
abstract:RATIONALE:B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315786
更新日期:2019-10-25 00:00:00
abstract::The patch-clamp technique was used to examine the inhibition of delayed rectifier K+ channels by agents that release intracellular Ca2+. During voltage-clamp experiments on isolated myocytes with 4-aminopyridine (4-AP, 10 mmol/L) and niflumic acid (100 mumol/L) present to inhibit delayed rectifier K+ current (IK(dr)) ...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/01.res.77.1.121
更新日期:1995-07-01 00:00:00
abstract::Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.160549
更新日期:2007-10-12 00:00:00
abstract::The isolated rat heart perfused with washed platelets was used as a model to examine platelet-vessel wall interactions. Release of prostacyclin and thromboxane A2 was measured, using a cascade of smooth muscle bioassay tissues or radioimmunoassays of the stable hydration products. In hearts perfused with rabbit or hum...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.1.172
更新日期:1986-01-01 00:00:00
abstract::The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving posttranscriptional regulation by small, noncod...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.192872
更新日期:2009-03-27 00:00:00
abstract::Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.38.6.2
更新日期:1976-06-01 00:00:00
abstract::We discuss the recent finding by Mizishima's group regarding the role of the autophagy-related conjugation system in mediating the closure of autophagosomes and its implication in the study of autophagy in mammalian cells. The study not only shows a novel function of the autophagy-related conjugation system but also i...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.117.310450
更新日期:2017-02-17 00:00:00
abstract::To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.570
更新日期:1986-04-01 00:00:00
abstract::The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.358
更新日期:1988-02-01 00:00:00
abstract::Mammalian cardiomyocytes irreversibly lose their capacity to proliferate soon after birth, yet the underlying mechanisms have been unclear. Cyclin D1 and its partner, cyclin-dependent kinase 4 (CDK4), are important for promoting the G1-to-S phase progression via phosphorylation of the retinoblastoma (Rb) protein. Mito...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000049105.15329.1c
更新日期:2003-01-10 00:00:00
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract:RATIONALE:Mammalian cardiomyocytes withdraw from the cell cycle during early postnatal development, which significantly limits the capacity of the adult mammalian heart to regenerate after injury. The regulatory mechanisms that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.248880
更新日期:2011-09-02 00:00:00
abstract::Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lacta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.5.829
更新日期:1994-05-01 00:00:00
abstract::Apolipoprotein E-deficient (ApoE-/-) mice develop atherosclerotic lesions throughout the arterial tree, including the carotid bifurcation. Although the expression of adhesion molecules such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin on endothelium that overlie atherosclerotic plaques has bee...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.11.1237
更新日期:1999-06-11 00:00:00
abstract:RATIONALE:The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.314438
更新日期:2019-04-12 00:00:00
abstract::Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.1.114
更新日期:1997-01-01 00:00:00
abstract::Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.1.9
更新日期:1999-01-08 00:00:00
abstract::In this study, anti-basic fibroblast growth factor (anti-bFGF) antibody was used to determine whether the mitogenic effect of angiotensin II in vivo could be blocked by neutralizing bFGF in the vessel wall. Animals, divided into six experimental groups, were given (1) angiotensin II, (2) angiotensin II + anti-bFGF ant...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.82.3.321
更新日期:1998-02-23 00:00:00
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
更新日期:2006-06-23 00:00:00
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
更新日期:1995-10-01 00:00:00
abstract::We tested the hypothesis that accumulation of H+ or inorganic phosphate (Pi) is responsible for the early contractile failure of hypoxia by measuring maximal Ca2+-activated pressure and 31P nuclear magnetic resonance spectra in Langendorff-perfused ferret hearts at 30 degrees C. Maximal Ca2+-activated pressure was ide...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.59.3.270
更新日期:1986-09-01 00:00:00
abstract::The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n = 11) or a 15-second occlusion at 4-minute intervals (group 2, n = 7) were repeated day and nig...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.2.287
更新日期:1989-02-01 00:00:00
abstract::Neuropeptide Y (NPY) is stored with norepinephrine in sympathetic nerves throughout the cardiovascular system and is released during activation of the sympathetic nervous system in humans and other animals. After stimulation of the cardiac sympathetic nerves in anesthetized dogs, the action of the vagus nerve on heart...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.193
更新日期:1990-07-01 00:00:00
abstract::Reperfusion of globally ischemic rat hearts causes the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and the initiation of arrhythmias. These responses are mediated by alpha1-adrenergic receptors (ARs), but the subtype of receptor involved has not been identified. Under normoxic conditions, hearts from tra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.12.1232
更新日期:1998-12-14 00:00:00
abstract:RATIONALE:Yes-associated protein (YAP), the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEA (transcriptional enhancer activator)-domain sequence-specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304457
更新日期:2015-01-02 00:00:00
abstract::The lung parenchyma as a tissue has a rather unusual stress-strain relationship. A theoretical derivation of this relationship is presented which connects the surface tension and the tissue elastic stress in the alveolar septa with the alveolar geometry. The mathematical expression contains a few meaningful physical c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.4.481
更新日期:1975-10-01 00:00:00
abstract::Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000064174.69165.66
更新日期:2003-03-21 00:00:00
abstract::We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were di...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1713
更新日期:1991-06-01 00:00:00
abstract::We examined the mechanism(s) of hypotensive action of platelet-activating factor (PAF) in anesthetized dogs. PAF (0.5 micrograms/kg i.v.) caused a biphasic hypotension; the first phase was transient and was accompanied by a decrease in systemic vascular resistance and an increase in cardiac output. Aspirin-DL-lysine, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.5.893
更新日期:1992-05-01 00:00:00