Abstract:
AIMS:Mobilization of stem cells/progenitors is regulated by the interaction between stromal cell-derived factor-1 (SDF-1) and its ligand, CXC chemokine receptor 4 (CXCR4). Statins have been suggested to ameliorate pulmonary arterial hypertension (PAH); however, the mechanisms involved, especially their effects on progenitors, are largely unknown. Therefore, we examined whether pravastatin ameliorates hypoxia-induced PAH in mice, and if so, which type of progenitors and what mechanism(s) are involved. METHODS AND RESULTS:Chronic hypoxia (10% O(2) for 5 weeks) increased the plasma levels of SDF-1 and mobilization of CXCR4(+)/vascular endothelial growth factor receptor (VEGFR)2(+)/c-kit(+) cells from bone marrow (BM) to pulmonary artery adventitia in Balb/c mice in vivo, both of which were significantly suppressed by simultaneous oral treatment with pravastatin (2 mg/kg/day). Furthermore, in vitro experiments demonstrated that hypoxia enhances differentiation of VEGFR2(+)/c-kit(+) cells into alpha-smooth muscle actin(+) cells. Importantly, pravastatin ameliorated hypoxia-induced PAH associated with a decrease in the number of BM-derived progenitors accumulating in the pulmonary artery adventitia. The expression of intercellular adhesion molecule-1 (ICAM-1) and its ligand, CD18 (beta2-integrin), were enhanced by hypoxia and were again suppressed by pravastatin. CONCLUSIONS:These results suggest that pravastatin ameliorates hypoxia-induced PAH through suppression of SDF-1/CXCR4 and ICAM-1/CD18 pathways with a resultant reduction in the mobilization and homing of BM-derived progenitor cells.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Satoh K,Fukumoto Y,Nakano M,Sugimura K,Nawata J,Demachi J,Karibe A,Kagaya Y,Ishii N,Sugamura K,Shimokawa Hdoi
10.1093/cvr/cvn244subject
Has Abstractpub_date
2009-01-01 00:00:00pages
226-34issue
1eissn
0008-6363issn
1755-3245pii
cvn244journal_volume
81pub_type
杂志文章abstract::Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused r...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(95)00181-6
更新日期:1995-12-01 00:00:00
abstract:AIMS:Following a large myocardial infarction (MI), remaining viable muscle often undergoes pathological remodelling and progresses towards chronic heart failure. Mitochondria may also be affected by this process and, due to their functional importance, likely contribute to the progression of the disease. Aerobic interv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt080
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:In many species arrhythmias induced by myocardial ischaemia appear to be in part dependent upon cardiac sympathetic nerves. However, previous experiments in rats did not suggest that myocardial or other catecholamines are involved in ischaemic arrhythmogenesis in this species. The aim of this study was to inv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00103-0
更新日期:1999-09-01 00:00:00
abstract::Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Di...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.2.232
更新日期:1976-03-01 00:00:00
abstract:OBJECTIVE:Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00309-6
更新日期:2001-03-01 00:00:00
abstract::Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.1.37
更新日期:1988-01-01 00:00:00
abstract::Infarct size can be limited by reducing the determinants of infarct size or increasing collateral blood flow by treatment initiated before the ischaemic event. Reperfusion is the definitive treatment for permanently reducing infarct size and restoring some degree of contractile function to the affected myocardium. Inn...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp129
更新日期:2009-07-15 00:00:00
abstract:AIMS:Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque hemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and ATF1. The anti-diabetic drug metformin may also activate AMPK-dependent signalling. HYPOTHESIS:Metformin systematically indu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa171
更新日期:2020-07-15 00:00:00
abstract::A pulsed, range gated, directional, ultrasonic, Doppler blood velocity meter was used to record signals from the pulmonary artery in 52 normal subjects ranging in age from less than 1 week to over 30 years. Signals were obtained from an unfocused transducer in the second or third left intercostal space using a 2.25 MH...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.11.816
更新日期:1986-11-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00143-0
更新日期:1997-10-01 00:00:00
abstract:AIMS:Treatment with the anticancer drug taxol (TXL), which polymerizes the cytoskeleton protein tubulin, may evoke cardiac arrhythmias based on reduced human cardiac sodium channel (Na(v)1.5) function. Therefore, we investigated whether enhanced tubulin polymerization by TXL affects Na(v)1.5 function and expression and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp352
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVE AND METHODS:In this study, we investigated whether Ca(2+) transients are altered in Purkinje cell aggregates dispersed from the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00725-3
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00068-6
更新日期:1998-09-01 00:00:00
abstract:AIMS:Alteration of connexin43 (Cx43)-mediated intercellular communication is known to promote susceptibility to ventricular tachyarrhythmias. However, the precise mechanism of the altered Cx43 responsible for arrhythmogenesis remains unclear. We sought to understand changes in impulse propagation of ventricular myocyte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn084
更新日期:2008-07-01 00:00:00
abstract::The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by bi...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs081
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVE:Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hyperch...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00353-5
更新日期:2003-07-01 00:00:00
abstract:STUDY OBJECTIVE:The objectives were (a) to describe the effects of vasoactive drugs in normal rats upon cardiovascular function assessed by computing aortic haemodynamic power and input impedance, each separated into their component parts, and (b) to study the relationship between left ventricular pulsatile power outpu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.11.923
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVE:The aim was to establish whether the duration of coronary ischaemia and coronary ischaemia with reperfusion selectively reduced the magnitude of relaxation mediated by endothelium dependent relaxing factor (EDRF) in response to thrombin, compared with relaxation produced by acetylcholine and calcimycin. METH...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.3.250
更新日期:1992-03-01 00:00:00
abstract:AIMS:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcriptional regulators. PPARdelta has an established role in metabolism, wound healing, and angiogenesis. However, little is known about its function in endothelial homeostasis. We investigat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp365
更新日期:2010-03-01 00:00:00
abstract:AIMS:Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced. In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. METHODS AND RESULTS:MCA (80-150 μm) isolated from wild-t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt157
更新日期:2013-10-01 00:00:00
abstract:AIMS:The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw233
更新日期:2017-01-01 00:00:00
abstract:AIM:To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS:ET-1 (0.013 microg/min) was infused to male ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00657-0
更新日期:2003-01-01 00:00:00
abstract::The effects of adrenaline on kinetically-distinct compartments of exchangeable calcium in the spontaneously-beating perfused rat heart were investigated under steady-state conditions using a 45Ca2+ outflow technique together with a nonlinear least-squares curve fitting procedure and 51Cr-EDTA to monitor the loss of fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.2.88
更新日期:1983-02-01 00:00:00
abstract:OBJECTIVES:M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS:We simulated action potent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.02.016
更新日期:2004-05-01 00:00:00
abstract:AIMS:Doxorubicin (DOX) is a widely used and effective anti-cancer therapeutic. DOX treatment is associated with both acute and late onset cardiotoxicity, limiting its overall efficacy. Here, the impact of cardiomyocyte cell cycle activation was examined in a juvenile model featuring aspects of acute and late onset DOX ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy273
更新日期:2019-04-15 00:00:00
abstract:AIMS:Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz305
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVES:Collagen synthesis is one of the major mechanisms of primary atherosclerotic plaque growth and is likely to be similarly important in restenosis. The patterns of collagen gene expression in human restenosis and associations with thrombosis/hemorrhage have not been described. METHODS:Using human coronary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract:OBJECTIVE:Chlamydia pneumoniae infection has been associated with atherosclerosis, although the mechanisms by which C. pneumoniae contribute to atherogenesis remain unclear. Altered production of nitric oxide, a known bactericidal and anti-inflammatory agent, represents one possible mechanistic link. To examine this is...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00389-4
更新日期:2003-10-15 00:00:00
abstract::Extracellular potassium activity before and after coronary occlusion was measured in the canine heart by means of potassium-selective surface electrodes. In the ischaemic myocardium potassium activity rapidly increased from a preocclusion value of 3.2 +/- 0.3 mmol.litre-1 to 10 +/- 0.6 mmol.litre-1 within the first 5 ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.5.297
更新日期:1979-05-01 00:00:00
abstract:OBJECTIVES:Epidemiological evidence in humans suggests that intrauterine growth retardation is associated with an increased risk of hypertension and coronary heart disease in later life. To begin to understand the mechanisms involved, we developed and exploited a rat model of intrauterine growth retardation to assess p...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00167-x
更新日期:2000-11-01 00:00:00