Abstract:
BACKGROUND:Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells. METHODS AND RESULTS:In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein. CONCLUSIONS:Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.
journal_name
Circulationjournal_title
Circulationauthors
Albrecht-Schgoer K,Schgoer W,Holfeld J,Theurl M,Wiedemann D,Steger C,Gupta R,Semsroth S,Fischer-Colbrie R,Beer AG,Stanzl U,Huber E,Misener S,Dejaco D,Kishore R,Pachinger O,Grimm M,Bonaros N,Kirchmair Rdoi
10.1161/CIRCULATIONAHA.111.076950subject
Has Abstractpub_date
2012-11-20 00:00:00pages
2491-501issue
21eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.111.076950journal_volume
126pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:In patients with coronary artery disease (CAD), acute thrombosis frequently occurs in coronary arteries with only mild or moderate stenoses. Obesity increases the risk of atherosclerosis, but it is not known whether it also increases the risk of coronary thrombosis. We hypothesized that body mass index (BMI)...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000095270.85646.E8
更新日期:2003-11-04 00:00:00
abstract:BACKGROUND:Data on outcomes after Stanford type A aortic dissection in patients with Marfan syndrome are limited. We investigated the primary surgery and long-term results in patients with Marfan syndrome who suffered aortic dissection. METHODS AND RESULTS:Among 1324 consecutive patients with aortic dissection type A,...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.113.005865
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular and bacterial pathogenetic mechanisms underlying the induction of BA are largely unknown. METHODS AND RESULTS:Activation of hypoxia-inducible factor-1 (HIF-1), t...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000155608.07691.B7
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:In patients with acute coronary syndromes and planned percutaneous coronary intervention, the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) demonstrated that treatment with prasugrel versus clopid...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.109.900704
更新日期:2010-01-05 00:00:00
abstract:BACKGROUND:Recurrent cerebrovascular events constitute an estimated 200,000 of the 700,000 strokes reported annually in the United States, which makes secondary stroke prevention an important goal in the management of disease among patients who have experienced stroke or transient ischemic attack. METHODS AND RESULTS:...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/CIRCULATIONAHA.106.653741
更新日期:2007-03-27 00:00:00
abstract:BACKGROUND:Insulin sensitivity and cardiovascular risk profile were examined in 20 healthy, nonobese, middle-aged men who were long-term users of nicotine-containing chewing gum and in 20 matched control subjects who did not use nicotine. METHODS AND RESULTS:Long-term use of nicotine-containing chewing gum was associa...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.5.878
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Integrins are involved in structural remodeling and tissue repair. This study aimed to elucidate the role of the beta-integrins in cardiac remodeling after myocardial infarction (MI). METHODS AND RESULTS:The MI model was created by ligation of the left anterior descending coronary artery in rats. We detecte...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000051363.86009.3c
更新日期:2003-02-25 00:00:00
abstract:BACKGROUND:Intimal smooth muscle cells (SMCs) contribute to the foam cell population in arterial plaque, and express lower levels of the cholesterol exporter ATP-binding cassette transporter A1 (ABCA1) in comparison with medial arterial SMCs. The relative contribution of SMCs to the total foam cell population and their...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.005015
更新日期:2014-04-15 00:00:00
abstract::A genetic-epidemiologic study was undertaken of a white Colorado population of 207 patients who had a myocardial infarction before age 55 years. Nineteen independent variables were compared between the 207 cases and 621 controls, matched 3:1. The highest risk ratios were associated with a positive family history for i...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.61.3.503
更新日期:1980-03-01 00:00:00
abstract::To determine if acute lung rejection after heart-lung transplantation can be detected noninvasively with indium-111-labeled (111In) lymphocytes, we studied 33 allogeneic and 18 isogeneic heterotopic heart-lung transplants in rats. Twenty-four hours after injection of isogeneic splenic 111In-lymphocytes (75 +/- 2 micro...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::The purpose of this study was to develop a clinically applicable system for quantifying premortem myocardial area at risk. Coronary artery occlusion was performed in 18 closed-chest dogs (11 left anterior descending and seven circumflex). 99mTc (15 mCi)-labeled macroaggregated albumin was then injected through an angi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.73.3.551
更新日期:1986-03-01 00:00:00
abstract::In previous studies from this laboratory, we found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular functio...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.70.3.357
更新日期:1984-09-01 00:00:00
abstract:BACKGROUND:It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary...
journal_title:Circulation
pub_type: 杂志文章,meta分析
doi:10.1161/01.cir.92.9.2419
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:High blood pressure (BP) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to elevated BP levels. We aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse BP gene...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCULATIONAHA.117.030898
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS:In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treat...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.95.10.2380
更新日期:1997-05-20 00:00:00
abstract:BACKGROUND:Recent studies suggest that mutations in cardiac mitochondrial DNA (mtDNA) may contribute to the development of dilated cardiomyopathy. The mechanisms that regulate those mutations, however, remain undefined. Thus, we studied cardiac mtDNA repair mechanisms, mtDNA damage, and mitochondrial structure and func...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc4501.098944
更新日期:2001-11-13 00:00:00
abstract:BACKGROUND:Coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy is increasing in frequency, as is reoperative bypass. However, there exist very little data on early outcomes of patients with severe left ventricular dysfunction undergoing reoperation. Hence, we tested the following hypotheses...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1997-11-04 00:00:00
abstract:BACKGROUND:There is no published randomized study comparing amiodarone therapy and radiofrequency catheter ablation (RFA) after only 1 episode of symptomatic atrial flutter (AFL). The aim of the Loire-Ardèche-Drôme-Isère-Puy-de-Dôme (LADIP) Trial of Atrial Flutter was 2-fold: (1) to prospectively compare first-line RFA...
journal_title:Circulation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCULATIONAHA.106.638395
更新日期:2006-10-17 00:00:00
abstract::The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency...
journal_title:Circulation
pub_type: 杂志文章,实务指引,评审
doi:10.1161/CIR.0000000000000541
更新日期:2017-12-05 00:00:00
abstract:BACKGROUND:Several echocardiographic dyssynchrony indexes have been proposed to identify responders to cardiac resynchronization therapy using tissue velocity and strain. The present study aimed to compare tissue velocity-derived and strain-derived dyssynchrony indexes in patients with or without systolic dysfunction a...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.733675
更新日期:2008-05-20 00:00:00
abstract:BACKGROUND:Smooth muscle cell (SMC) migration and proliferation critically influence the clinical course of vascular disease. We tested the effect of the novel small leucine-rich repeat protein podocan on SMC migration and proliferation using a podocan-deficient mouse in combination with a model of arterial injury and ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.004634
更新日期:2013-11-26 00:00:00
abstract:BACKGROUND:During the development of heart failure (HF), the chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac energy substrate preferences, is thought to maintain aerobic energetic balance. The regulatory mechanisms involved in this metabol...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.11.2837
更新日期:1996-12-01 00:00:00
abstract::To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.68.5.1062
更新日期:1983-11-01 00:00:00
abstract:BACKGROUND:The present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity. METHODS AND RESULTS:The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patient...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.85.5.1751
更新日期:1992-05-01 00:00:00
abstract::Intermittent aortic root infusion of a cold solution containing either potassium chloride (KCl) or diltiazem was performed in 32 dogs during a 2-hour aortic clamping. Half of the dogs in each group had a critical stenosis created on the circumflex artery before cardiopulmonary bypass. Global left ventricular (LV) func...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.65.6.1078
更新日期:1982-06-01 00:00:00
abstract:BACKGROUND:Transfer of the coronary arteries is a crucial step during the arterial switch operation (ASO) for transposition of the great arteries. This retrospective study aims to assess the incidence and risk factors of coronary events after ASO and sensitivity of noninvasive tests in the diagnosis of the coronary obs...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000087902.67220.2b
更新日期:2003-09-09 00:00:00
abstract:BACKGROUND:Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L ha...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.699173
更新日期:2008-03-11 00:00:00
abstract:BACKGROUND:Short-term hibernating myocardium is characterized by a decrease in contractile function in proportion to the reduced myocardial blood flow. Myocardial creatine phosphate content, initially decreased during the first minutes of ischemia, returns to near-control values, the ischemia-induced net lactate produc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.2.684
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:Roux-en-Y gastric bypass (RYGB) reduces body weight and cardiovascular mortality in morbidly obese patients. Glucagon-like peptide-1 (GLP-1) seems to mediate the metabolic benefits of RYGB partly in a weight loss-independent manner. The present study investigated in rats and patients whether obesity-induced ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.011791
更新日期:2015-03-10 00:00:00
abstract:BACKGROUND:The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear. METHODS AND RESULTS:We simultaneously mapped epicardial membrane potential and Ca(i) during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. U...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.630509
更新日期:2006-12-12 00:00:00