Abstract：
OBJECTIVE:Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. METHODS:In rabbits (n=7 per group), the external femoral artery was excised at day 0 (d0). At d7, liposomes containing eGFP (control group) or Hsp90 were retroinfused into the anterior tibial vein. At day 7 and day 35, angiographies were obtained and analyzed for collateral formation and perfusion velocity (frame count score) (% of d7 values). Capillary/muscle fiber (C/MF) ratio was calculated from five muscle areas of the ischemic limb. L-NAME and Geldanamycin were co-applied, where indicated. RESULTS:Compared to mock-treated controls, Hsp90 transfected increased C/MF ratio at day 35 (1.78+/-0.15 vs. 1.19+/-0.13, p<0.05), an effect blunted by L-NAME (1.39+/-0.11). Hsp90 transfection increased collateral formation (157+/-11% vs. 110+/-13%) and frame count score (174+/-18% vs. 117+/-10%), both sensitive to inhibition by L-NAME coapplication (135+/-17% and 134+/-14%, respectively). Of note, C/MF ratio was found elevated 3 days after Hsp90 transfection (1.61+/-0.16 at d10), at a time point when collateral formation was unchanged (106+/-6%), and tended to remain elevated in the presence of L-NAME applied thereafter (1.64+/-0.35 at d35), though L-NAME blocked subsequent changes in collateral growth or increase in perfusion at d35. CONCLUSIONS:We conclude that Hsp90 is capable of inducing angiogenesis and arteriogenesis via nitric oxide (NO) in a rabbit model of chronic ischemia. Our findings describe the capillary level as an initial site of Hsp90-cDNA-induced neovascularization, followed by growth of larger conductance vessels, resulting in an improved hindlimb perfusion.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Pfosser A,Thalgott M,Büttner K,Brouet A,Feron O,Boekstegers P,Kupatt Cdoi
10.1016/j.cardiores.2004.10.019subject
Has Abstractpub_date
2005-02-15 00:00:00pages
728-36issue
3eissn
0008-6363issn
1755-3245pii
S0008-6363(04)00466-3journal_volume
65pub_type
杂志文章abstract：:Atherosclerosis is considered to be a form of chronic inflammation governed by a complex network of inter- and intra-cellular signaling pathways. The pleiotropic cytokine interferon-gamma (IFN-gamma) is a key pro-inflammatory mediator that is expressed at high levels in atherosclerotic lesions. IFN-gamma regulates the...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2005.04.019
更新日期：2005-07-01 00:00:00
abstract：AIMS:This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta. METHODS AND RESULTS:Aortic segments from orchidectomized and control male Sprague-Dawley ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvm059
更新日期：2008-02-01 00:00:00
abstract：:It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac C...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2004.02.010
更新日期：2004-05-01 00:00:00
abstract：:The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved an...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/s0008-6363(97)00293-9
更新日期：1998-03-01 00:00:00
abstract：OBJECTIVES:The concept of lethal reperfusion injury in ischemic myocardium has been the subject of controversy. Adenosine administered during reperfusion has been reported to limit lethal reperfusion injury in several studies. On the contrary, it has been reported that cardioprotection may not be achieved with adenosin...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/0008-6363(95)00235-9
更新日期：1996-05-01 00:00:00
abstract：OBJECTIVE:Pericytes, located in close proximity to the underlying endothelium, form an integral component of the microvasculature. These cells are intimately involved in angiogenesis, which is of fundamental importance in many physiological and pathological processes. We evaluated the influence of pericyte-conditioned ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.08.003
更新日期：2006-01-01 00:00:00
abstract：:Postextrasystolic potentiation was studied by means of a catheter-tip manometer in patients with and without cardiomyopathy. The results imply that the enhancement of the left ventricular contraction is increased in patients with cardiomyopathy. ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/9.3.336
更新日期：1975-05-01 00:00:00
abstract：OBJECTIVE:Experimental evidence suggests that modulation of myocardial substrate metabolism can markedly affect the progression of chronic heart failure (HF). We tested whether the inhibition of carnitine palmitoyl transferase-I (CPT-I), the enzyme regulating mitochondrial fatty acid oxidation, slows left ventricular r...
journal_title：Cardiovascular research
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doi：10.1016/j.cardiores.2005.02.004
更新日期：2005-06-01 00:00:00
abstract：:End-diastolic current thresholds have been measured in 12 open-chested dogs with epicardial disc electrodes ranging in radius from 0.01 to 9.0 mm. The current threshold for cathodal 1 ms impulses proved to be independent of electrode size for radii smaller than 0.2 mm and proportional to the radius to the power 1.5 fo...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/12.8.477
更新日期：1978-08-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/14.5.288
更新日期：1980-05-01 00:00:00
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journal_title：Cardiovascular research
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更新日期：2011-09-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/26.7.662
更新日期：1992-07-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2006.02.023
更新日期：2006-05-01 00:00:00
abstract：:Primary cardiomyopathy is an important cause of mortality in children and adults. Apart from inherited disorders of myocardial contractile and structural proteins, several defects of energy metabolism may cause cardiomyopathy. Most of the energy required for myocardial contraction is derived from aerobic metabolism. F...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/s0008-6363(97)00141-7
更新日期：1997-08-01 00:00:00
abstract：CONDENSED ABSTRACT:We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricu...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00164-3
更新日期：1998-12-01 00:00:00
abstract：BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...
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pub_type： 杂志文章
doi：10.1016/s0008-6363(00)00320-5
更新日期：2001-04-01 00:00:00
abstract：OBJECTIVE:Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS:Right atrial appendages were obtained from eight patients with paroxysmal AF, ten ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(99)00045-0
更新日期：1999-05-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00700-9
更新日期：2003-02-01 00:00:00
abstract：:Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, t...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvs111
更新日期：2012-07-15 00:00:00
abstract：OBJECTIVE:Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, L-NG-monomethylarginine (L-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. METHODS:Blood f...
journal_title：Cardiovascular research
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.03.010
更新日期：2005-07-01 00:00:00
abstract：OBJECTIVES:The purpose of this study was to investigate the changes in beta-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopa...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:When the vagus nerves are stimulated with one burst of pulses per minute, but each burst is placed at a different time in the cardiac cycle, a "vagal effect curve" can be derived which displays the changes in cardiac cycle length (CCL) as a function of the elapsed time from the stimulus. This curve consists of a prima...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/18.2.75
更新日期：1984-02-01 00:00:00
abstract：:Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvy006
更新日期：2018-03-15 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00536-3
更新日期：2002-03-01 00:00:00
abstract：OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(99)00144-3
更新日期：1999-09-01 00:00:00
abstract：:The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/19.9.570
更新日期：1985-09-01 00:00:00
abstract：:Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of mat...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2004.06.006
更新日期：2004-10-01 00:00:00
abstract：AIMS:Hypertension is a risk factor for atherothrombotic vascular events. Angiotensin II (Ang II), one of the main vasoactive hormones of the renin-angiotensin system, has been associated with the development and progression of atherosclerosis. However, it is not fully known how Ang II contributes to lipid-enriched athe...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn043
更新日期：2008-06-01 00:00:00
abstract：AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce T...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr102
更新日期：2011-08-01 00:00:00
