European Journal of Clinical Investigation (Eur J Clin Investig )

Publisher: European Society for Clinical Investigation, Blackwell Publishing

Description

The Journal of the European Society for Clinical Investigation. The European Journal of Clinical Investigation publishes papers in the field of clinical investigation, provided they contribute to the advancement of knowledge in this field. The term 'clinical investigation' is interpreted widely and includes studies relevant to humans in health or disease, including such studies that may have taken place with animals.

  • Impact factor
    3.37
  • 5-year impact
    3.05
  • Cited half-life
    8.00
  • Immediacy index
    0.70
  • Eigenfactor
    0.01
  • Article influence
    0.90
  • Website
    European Journal of Clinical Investigation website
  • Other titles
    European journal of clinical investigation (Online)
  • ISSN
    1365-2362
  • OCLC
    46653881
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher version cannot be used
    • On author or institutional or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com ")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley-Blackwell'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is controversy regarding the effect of alcohol beverage intake in vascular vasodilatory function in peripheral arteries. The effects of beer intake in coronary vasodilation remain unknown. We investigated whether regular beer intake (alcohol and alcohol-free) protects against hypercholesterolemia-induced coronary endothelial dysfunction and the mechanisms behind this effect.
    European Journal of Clinical Investigation 10/2014;
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    ABSTRACT: Estrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving estrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of estrogen-induced cholesterol gallstones in mice.
    European Journal of Clinical Investigation 10/2014;
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    ABSTRACT: Background/Objectives The impact of an elevation of cardiac biomarkers occurring after percutaneous coronary intervention (PCI) on long-term outcome remains controversial. Most available data are based on observational registries using multivariable analysis. In the present study, a case control approach was used to assess separately the impact of post-PCI elevation of CK-MB on the short-term in-hospital outcome and on the long-term outcome after hospital discharge.Methods Between 01.01.1996 and 31.12.2008, a post-procedural rise of CKMB was observed in 363 among 8346 consecutive PCI procedures (4.3%). The overall in-hospital mortality for patients with or without CKMB elevation after PCI was 8.5% and 1.5% respectively (p<0.001). For 245 hospital survivors with CKMB elevation, we found 245 control cases matched for 9 relevant clinical parameters in our PCI database during the same period. The long-term survival of these patients was assessed by KM estimates.ResultsDespite an increased in-hospital mortality among patients with peri-procedural elevation of CKMB, the long-term outcome of patients who are discharged alive is independent of CKMB release, curves of overall survival and of survival free of recurrence of myocardial infarction being similar up to 10 years after hospital discharge.Conclusions In our population, the elevation of CKMB after PCI identified a high risk subgroup for in-hospital mortality but had no impact on the long-term prognosis, once the patient is discharged alive from the hospital.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
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    ABSTRACT: Background Elevated levels of fibroblast growth factor 23 (FGF23) are associated with incident heart failure in individuals with or without chronic kidney disease. We aimed to investigate the association between serum FGF23 concentrations and disease severity and long-term outcome in patients with stable heart failure.Materials and methodsSerum levels of C-term FGF23 (Ct-FGF23) concentrations, inorganic phosphate (Pi), parathormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were measured in 208 patients with non-ischemic heart failure (age 48±15 years; 70% male; NYHA Class I 27.8%, NYHA Class II 43.4%, NYHA Class III/IV 28.8%; LV-EF 34±15%; eGFR ≥60ml/min/1.73m2 in 86%).ResultsMedian Ct-FGF23 levels were 18.2 RU/ml (7.5-40.8RU/ml). A dose-response relationship was found between median Ct-FGF23 levels and increasing NYHA class (I: 11.9 RU/ml, II: 15.8 RU/ml, III/IV: 38.8 RU/ml; p<0.001). Ct-FGF23 correlated with NTproBNP (r=0.307, p<0.001), central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and inversely correlated with cardiac output after adjustment for renal function (eGFR) and Pi. LnCt-FGF23 was related with the combined endpoint of death or heart transplantation (hazard ratio 1.452 [1.029 to 2.048]; p=0.034) independent of Pi, PTH, 25(OH)D, age and sex.Conclusion The phosphatonin FGF23 is strongly associated with disease severity and long-term outcome in patients with non-ischemic heart failure and preserved renal function. Further studies are needed to evaluate the pathophysiologic role of FGF23 and its potential as a biomarker in heart failure.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
  • Mai Takiguchi, Akiomi Yoshihisa, Shunsuke Miura, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Shoji Iwaya, Takashi Owada, Makiko Miyata, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Hitoshi Suzuki, Shu‐ichi Saitoh, Yasuchika Takeishi
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    ABSTRACT: Background Higher body mass index (BMI) is associated with incident heart failure (HF), but paradoxically associated with better prognosis, recognized as the obesity paradox in HF. However, the impact of BMI on detailed prognosis on HF and the mechanism of obesity paradox remain still unclearMethods We researched consecutive 648 patients admitted for HF: Underweight (BMI < 18.5 kg/m2, n=86), Normal (18.5 ≤ BMI < 25, n=380), Overweight (25 ≤ BMI <30, n=147), and Obese (30 ≤ BMI, n=35), and compared the results from their laboratory tests and echocardiography. We also followed cardiac and all-cause mortalityResultsObese group had a higher prevalence of obesity-related co-morbidity (hypertension, diabetes, dyslipidemia), however, tumor necrosis factor-α, adiponectin, troponin T, and systolic pulmonary arterial pressure were higher in the Underweight group than in the other groups (P<0.05, respectively). Left and right ventricular systolic function did not differ among the groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality progressively increased from Obese to Overweight, Normal and Underweight group. Importantly, in the Cox proportional hazard analyses after adjusting for known risk factors, BMI was an independent predictor of cardiac and all-cause mortality (P<0.01, respectively) in HF patientsConclusionsBMI was an independent predictor of cardiac death and all-cause mortality in HF patients. Furthermore, lower BMI was associated with higher circulating levels of tumor necrosis factor-α, adiponectin and troponin T, and higher systolic pulmonary arterial pressureThis article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
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    ABSTRACT: Background Erosive esophagitis (EE) may be complicated by esophageal ulcers, peptic stricture, Barrett's esophagus and esophageal adenocarcinoma. There have been few studies examining the influence of nonalcoholic fatty liver disease (NAFLD) on EE, and even fewer exploring the simultaneous effects of NAFLD, general and central obesity on EE. We thus aim to clarify the relationship between NAFLD and EE when general and/or central obesity are considered simultaneously.Materials and methodsIn this cross-sectional study, we enrolled 12,090 subjects who underwent a health checkup at the Health Examination Center of a university hospital between January 2000 and August 2009 for analysis. NAFLD was diagnosed using liver ultrasound and EE was defined according to the Los Angeles classification by esophagogastroduodenoscopy.ResultsSubjects with EE (1,922; 15.9%) had a higher proportion of NAFLD, general and central obesity. With adjustment for age, gender, hypertension, diabetes mellitus, hiatal hernia, hypertriglyceridemia, high-density lipoprotein cholesterol, alcohol consumption, tea drinking, smoking and habitual exercise, the results of the multivariate analyses showed that general obesity, central obesity and NAFLD were all significantly associated with EE in their separate models. When considering general obesity, central obesity and NAFLD simultaneously, NAFLD, but neither general nor central obesity, remained positively correlated to EE. In addition, male gender, hiatal hernia and hypertriglyceridemia were all significantly associated with EE.Conclusion In addition to general and central obesity, NAFLD is independently associated with increased risk of EE, and the detrimental effect of NAFLD on EE might be greater than those of general and central obesity.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
  • Kun‐Ta Chou, Chen‐Chi Liu, Han‐Shui Hsu, Shi‐Chuan Chang, Yuh‐Min Chen, Diahn‐Warng Perng, Yuan‐Tong Hsu, Yu‐Chin Lee, Shih‐Chieh Hung
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    ABSTRACT: Background Patients with obstructive sleep apnea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA.Methods Thirty-five OSA patients and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnea-hyponea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or their difference. Correlation analysis was done to identify factors related to stem cell mobilizationResultsCompared to controls, the nocturnal ratios and difference of CD34+ cell level were larger in OSA patients (ratios: 1.141 vs. 0.896, p=0.036; difference: 340 vs. -166 /cc blood, p=0.036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI、body mass index (BMI)、SpO2 nadir、oxygen desaturation index and time sustaining hypoxemia. After adjusting age, gender and BMI, AHI (r=0.357, p=0.016) and hypoxemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (p=0.009) and SDF-1α (p=0.001) were also significant in OSA patients, but not in controls. After CPAP therapy for 6 months, the elevated mobilization ratios in OSA patients tended to decline (p=0.059).ConclusionCD34+ stem cell mobilization during sleep was observed in OSA.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
  • Silvia Ruiz‐Gaspà, Marta Dubreuil, Nuria Guañabens, Andrés Combalia, Pilar Peris, Ana Monegal, Albert Parés
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    ABSTRACT: Background Low bone turnover osteoporosis is common in cholestatic diseases. Ursodeoxycholic acid (UDCA) counteracts the damaging effects of bilirubin or lithocholic acid (LCA) on osteoblast viability, proliferation and mineralization. UDCA is antiapoptotic in various cell lines, but this effect in bone cells is unknown. Therefore, the consequences of bilirubin and LCA on apoptosis, and if UDCA has antiapoptotic effects have been assessed on osteoblasts.Materials and Methods Human osteoblasts (hOB), and osteosarcoma cell line (Saos-2) were treated with camptothecin as a proapoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, flow cytometry, caspase-3 activity, and expression of proapoptotic (Bcl-2–associated X protein BAX), and antiapoptotic (BCL2 and BCL2-like 1 protein, BCL2L) genes.ResultsBoth LCA (10 μM) and bilirubin (50 μM) induced apoptosis as indicated by DNA fragmentation (4.7 and 3.7 fold, respectively, p<0.001), caspase-3 activity and flow cytometry in Saos-2 and hOB. UDCA (10 μM) reduced the apoptotic effects of camptothecin (0.5 μM) by 61%, (p<0.001), and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively, p<0.001), cytometry and caspase-3 activity in Saos-2, with lower effects in hOB. UDCA (10 μM) downregulated BAX (75%), and upregulated BCL2L (10-fold, p<0.01) genes, and neutralized BAX upregulation (p<0.01) and BCL2L downregulation (p<0.01) induced by LCA and bilirubin.Conclusions Bilirubin and LCA induce apoptosis in osteoblastic cells. UDCA counteracts the apoptotic consequences of these two substances and therefore, it may have further beneficial effects on the decreased bone formation in the cholestasis.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2014;
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    ABSTRACT: Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different drugs, safety and efficacy of statin treatment have been widely investigated and proven.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: We examined the degree of postprandial triglyceride (TG) response over the day, representing a highly dynamic state, with continuous metabolic adaptations, among normal weight, overweight and obese patients, according to their metabolically healthy or abnormal status.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Coupled arterial and left ventricular properties are poorly documented in acute heart failure. The aim of this prospective non invasive study was to document early changes in ventricular-arterial coupling in patients with acutely decompensated HF (ADHF).
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Both hyperuricaemia and left ventricular (LV) hypertrophy are associated with the metabolic syndrome and increased cardiovascular risk. The relationship between uric acid levels and left ventricular mass in hypertension, however, is unclear. In this study, we have investigated this relationship in hypertensive patients without the metabolic syndrome.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Objectives The post cardiac arrest syndrome occurs after global hypoxia leading to microcirculatory impairment. Nitric oxide (NO) is a key molecule regulating microvascular function. The enzyme arginase has been suggested to modulate microvascular function by regulating NO metabolism. Therefore we investigated whether arginase increase following global hypoxia and resuscitation and tested whether arginase inhibition influences altered microcirculation in resuscitated patients.Methods To determine the effect of global hypoxia on circulating arginase levels, fourteen healthy subjects were exposed to hypoxia in a normobaric hypoxia chamber (FiO²=9.9%). In addition, 31 resuscitated patients were characterized clinically and arginase 1 was measured on day 1 and day 3. In eight resuscitated patients, a microcirculatory analysis was performed using a sidestream darkfield microcirculation camera. Perfused capillary density (PCD) was recorded before and after sublingual incubation of N-omega-hydroxy-nor-L-arginine (nor-NOHA) alone or together with the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA).ResultsCirculating arginase 1 levels increased in healthy volunteers following global hypoxia in the hypoxic chamber (p<0.01). In addition, arginase 1 levels were higher on day 1 (69.1 ± 83.3 ng/ml) and on day 3 (44.2 ± 65.6 ng/ml) after resuscitation than in control subjects (p<0.001). Incubation of the sublingual mucosa with nor-NOHA increased microcirculatory perfusion (p<0.001). This effect was inhibited by co-incubation with L-NMMA.Conclusions Circulating arginase 1 levels are increased following exposure to global hypoxia and in patients that have been successfully resuscitated after cardiac arrest. Topical arginase inhibition improves microcirculatory perfusion following resuscitation. This is of potential therapeutic importance for the post-cardiac arrest syndrome.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Objective We conducted a nationwide population-based cohort study to investigate the effects of asthma on the risk of stroke development in an Asian population.Methods Newly diagnosed asthmatic patients aged ≧ 18 years were identified, and asthma-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year by using records obtained from the National Health Insurance Research Database between 2000 and 2010. Both cohorts were followed up until the end of 2011 to measure the incidence of stroke. The risk of stroke was analyzed using Cox proportional hazard regression models, including factors such as sex, age, and comorbidities.ResultsWe followed the asthmatic patients for 104 697 person-years and followed the nonasthmatic people for 426 729 person-years. The incidence density rate of stroke increased in all of the groups of asthmatic patients compared with that of the controls when stratified according to sex, age, and comorbidities. The hazard ratio (HR) of stroke was 1.37-fold greater for the asthmatic cohort, compared with that for the nonasthmatic cohort, after adjusting for sex, age, and comorbidities. The adjusted HR of developing stroke substantially increased with older age and the increased frequency of asthmatic exacerbation and hospitalization. The patients receiving beta-2 agonists as a treatment exhibited a significantly greater risk of stroke compared with the patients receiving only inhaled corticosteroids, after adjusting for covariates.Conclusion Asthma may be an independent risk factor for stroke, and its severity exhibits a dose response of stroke development.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: We would like to thank Dr Kim's and Park's for the points raised in their letter which focus on the statistical analyses of our study concerning the prevalence of primary aldosteronism in hypertensive patients [1]. We would like to address their points one by one.The first point raised by the authors of the letter concerns the correlation coefficient that we used in Figure 2. Indeed they are right; it is the Spearman's correlation coefficient. In addition, we fully agree with them that most of the distributions in Figure 2 are skewed.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Background Twist and Snail are considered as key transcriptional repressors of E-cadherin tightly related to epithelial-to-mesenchymal transition (EMT) and cancer progression. Numerous studies have investigated the prognostic value of Twist and Snail. However, the published results were controversial or even opposite. Our article aimed to evaluate the prognostic role of Twist and Snail in patients with cancer.DesignA comprehensive literature search of PubMed, Embase, and Web of Science was conducted. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were assessed to quantify the prognostic role.ResultsThe pooled HR with 38 studies for Twist was 2.18 (95%CI: 1.77-2.68, I2=69.8%, p=0.000) and for Snail with 40 studies was 1.58 (95%CI: 1.33-1.87, I2=70.0%, p=0.000), suggesting high Twist/Snail expression predicted poor prognosis related to all clinical outcomes. For Twist, the pooled HR for overall survival (OS) was 2.07 (95%CI: 1.63-2.63, I2=72.6%, p=0.000), and for progression-free/recurrence-free/metastasis-free/disease-free/cancer-free survival (PFS/RFS/MFS/DFS/CFS) was 2.36 (95%CI: 1.76-3.17, I2=65.0%, p=0.000). For Snail, the pooled HR for OS was 1.63 (95%CI: 1.33-1.99, I2=70.8%, p=0.000), and for PFS/RFS/MFS/DFS/CFS was 1.54 (95%CI: 1.17-2.02, I2=59.1%, p=0.001). All of those results suggesting that high Twist/Snail expression was associated with poor prognosis. Furthermore, when grouped into different types of cancers, the pooled HRs were also calculated for the subgroups. No publication bias was found except studies evaluating all clinical outcomes of Twist (p =0.006 for Begg's test and 0.006 for Egger's test).Conclusions Elevated Twist or Snail expression in tumor tissue indicated poor prognosis for cancer.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Background Patients with continuous ambulatory peritoneal dialysis (CAPD) have high all-cause mortality risk that varies extensively among different conditions. The objective of this study was to develop and validate risk models to predict the 2-year all-cause mortality risks of CAPD patients.Material and MethodsA total of 1,354 patients who received CAPD treatment >3 months from a single dialysis center were enrolled into the study from January 1, 2006 to December 31, 2011 and followed up until June 30, 2013. The dataset was randomly divided into the derivation dataset (2/3, n=903) and the validation dataset (1/3, n=451). Baseline information, including demographic characteristics, comorbid conditions, and laboratory data, was recorded and included in the models. Risk models were developed using Cox proportional hazards regression. C-statistic, Akaike Information Criterion, Hosmer-Lemeshow χ2 test, and net reclassification improvement (NRI) were performed to evaluate model prediction and validation.ResultsDuring the entire follow-up period, 175 (19.38%) and 85 (18.85%) patients died in the derivation and validation datasets, respectively. A model that included age, diabetes mellitus, hypertension, cardiovascular disease, diastolic blood pressure, serum albumin, serum creatinine, phosphate, hemoglobin, and fasting blood glucose demonstrated good discrimination in the derivation and validation datasets to predict 2-year all-cause mortality (C-statistic, 0.790 and 0.759, respectively). In the validation dataset, the above model performed good calibration (χ2=2.08, P=0.98) and NRI (7.37% compared with model 2, P=0.05).Conclusions The risk model can accurately predict 2-year all-cause mortality in Chinese CAPD patients and external validation is needed in future.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;
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    ABSTRACT: Background Cardiovascular patients suffer from reduced blood flow leading to ischemia and impaired tissue metabolism. Unfortunately, an increasing group of elderly patients cannot be treated with current revascularization methods. Thus, new treatment strategies are urgently needed. Hypoxia inducible factors (HIFs) upregulate the expression of angiogenic mediators together with genes involved in energy metabolism and recovery of ischemic tissues. Especially, HIF-2α is a novel factor and only limited information is available about its therapeutic potential.Methods Gene transfers with adenoviral HIF-1α and HIF-2α were done into the mouse heart and rabbit ischemic hindlimbs. Angiogenesis was evaluated by histology. Left ventricle function was analysed with echocardiography. Perfusion in rabbit skeletal muscles and energy recovery after electrical stimulation-induced exercise were measured with ultrasound and 31P-magnetic resonance spectroscopy (31P-MRS), respectively.ResultsHIF-1α and HIF-2α gene transfers increased capillary size up to 5-fold in myocardium and ischemic skeletal muscles. Perfusion in skeletal muscles was increased by 4-fold without edema. Especially AdHIF-1α enhanced the recovery of ischemic muscles from electrical stimulation-induced energy depletion. Special characteristic of HIF-2α gene transfer was a strong capillary growth in muscle connective tissue and that HIF-2α gene transfer maintained left ventricle function.Conclusions We conclude that both AdHIF-1α and AdHIF-2α gene transfers induced beneficial angiogenesis in vivo. Transient moderate increases in angiogesis improved energy recovery after exercise in ischemic muscles. This study shows for the first time that a moderate increase in angiogenesis is enough to improve tissue energy metabolism which is potentially a very useful feature for cardiovascular gene therapy.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2014;