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Sökning: LAR1:gu > Gan Li Ming

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1.
  • Adingupu, D. D., et al. (författare)
  • Radial artery intima-media thickness regresses after secondary prevention interventions in patients' post-acute coronary syndrome and is associated with cardiac and kidney biomarkers
  • 2017
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:32, s. 53419-53431
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Radial artery intima-media thickness (rIMT) measured by ultra-high-resolution ultrasound is associated with increased cardiovascular risk and predicts outcomes. We performed non-invasive high-resolution ultrasound of the radial artery to investigate vascular changes in subjects presenting with acute coronary syndrome (ACS) and who had undergone percutaneous coronary intervention (PCI). Purpose: In the present work, we aimed to follow rIMT change over time post-acute coronary syndrome as a tool to monitor potential response to intensified medical therapy. Methods: We examined 256 subjects who underwent PCI due to ACS and healthy controls (n= 39) and we measured a number of biomarkers, which are known to be associated with cardiovascular disease. Images of radial artery were acquired bilaterally in the longitudinal view using a 50 MHz transducer (Vevo 2100 VisualSonics, Inc, Toronto, Ontario, Canada). Carotid IMT (cIMT) and rIMT were measured at <1 month after index PCI followed by a repeated measurement of rIMT at 4 months from the ACS in a sub-set (n= 117). Results: rIMT measured within 1 month post ACS was significantly higher than rIMT after 4 months from ACS, (p < 0.0001), mean +/- SD (rIMT right 0.35 +/- 0.08; rIMT left 0.37 +/- 0.08) vs. (rIMT right 0.29 +/- 0.08; rIMT left 0.31 +/- 0.09) respectively. There was no statistically significant change in cIMT. In healthy controls there were no changes in rIMT or cIMT overtime. High levels of CX3CL1 and myeloperoxidase measured within one month post ACS are associated with increase of rIMT, r=0.38 (p< 0.0001) and r=0.41 (p< 0.0001) respectively. Conclusions: rIMT seem to decrease systemically after ACS and is accompanied with corresponding biomarker change. The cause and clinical implications of the observed decrement in rIMT after ACS need further studies.
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2.
  • Adingupu, D. D., et al. (författare)
  • SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob(-/-) mice
  • 2019
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) is the first class of anti-diabetes treatment that reduces mortality and risk for hospitalization due to heart failure. In clinical studies it has been shown that SGLT2i's promote a general shift to fasting state metabolism characterized by reduced body weight and blood glucose, increase in glucagon/insulin ratio and modest increase in blood ketone levels. Therefore, we investigated the connection between metabolic changes and cardiovascular function in the ob/ob(-/-) mice; a rodent model of early diabetes with specific focus on coronary microvascular function. Due to leptin deficiency these mice develop metabolic syndrome/diabetes and hepatic steatosis. They also develop cardiac contractile and microvascular dysfunction and are thus a promising model for translational studies of cardiometabolic diseases. We investigated whether this mouse model responded in a human-like manner to empagliflozin treatment in terms of metabolic parameters and tested the hypothesis that it could exert direct effects on coronary microvascular function and contractile performance.MethodsLean, ob/ob(-/-) untreated and ob/ob(-/-) treated with SGLT2i were followed for 10weeks. Coronary flow velocity reserve (CFVR) and fractional area change (FAC) were monitored with non-invasive Doppler ultrasound imaging. Food intake, urinary glucose excursion and glucose control via HbA1c measurements were followed throughout the study. Liver steatosis was assessed by histology and metabolic parameters determined at the end of the study.ResultsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) animals resulted in a switch to a more catabolic state as observed in clinical studies: blood cholesterol and HbA1c were decreased whereas glucagon/insulin ratio and ketone levels were increased. SGLT2i treatment reduced liver triglyceride, steatosis and alanine aminotransferase, an indicator for liver dysfunction. l-Arginine/ADMA ratio, a marker for endothelial function was increased. SGLT2i treatment improved both cardiac contractile function and coronary microvascular function as indicated by improvement of FAC and CFVR, respectively.ConclusionsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) mice mimics major clinical findings regarding metabolism and cardiovascular improvements and is thus a useful translational model. We demonstrate that SGLT2 inhibition improves coronary microvascular function and contractile performance, two measures with strong predictive values in humans for CV outcome, alongside with the known metabolic changes in a preclinical model for prediabetes and heart failure.
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3.
  • Ambring, Anneli, 1964, et al. (författare)
  • Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects.
  • 2006
  • Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 83:3, s. 575-81
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Reduced cardiovascular mortality and morbidity have been shown in persons adhering to Mediterranean-inspired diets (MIDs). Although the underlying mechanisms of this association are poorly understood, the importance of increasing dietary amounts of polyunsaturated fatty acids of the n-3 series has been emphasized. OBJECTIVE: We investigated whether a MID provided to healthy subjects would affect 1) the inflammatory process and endothelial indexes such as vasoregulation and vascular endothelial growth factor (VEGF) and 2) serum phospholipid fatty acid composition. DESIGN: A total of 22 subjects (10 women) received a MID or an ordinary Swedish diet (OSD) for 4 wk in a crossover fashion. Concentrations of lipids and fatty acids, high-sensitivity C-reactive protein, and interleukin 6, both before and after lipopolysaccharide stimulation; the number of leukocytes and platelets; and VEGF and monocyte chemoattractant protein 1 were analyzed. RESULTS: The plasma ratio of n-6 to n-3 fatty acids was substantially lower after the MID than after the OSD (x +/- SEM: 4.72 +/- 0.19 and 2.60 +/- 0.17, respectively; P < 0.0001). Neither C-reactive protein nor interleukin 6 concentrations changed significantly after the MID compared with the OSD. The total number of leukocytes and platelets was 10% (P < 0.05) and 15% (P < 0.001) lower, respectively, after the MID than after the OSD. Serum VEGF concentrations were lower after the MID than after the OSD (237 +/- 30 and 206 +/- 25 pg/mL, respectively; P = 0.0014). CONCLUSIONS: A MID reduces the number of platelets and leukocytes and VEGF concentrations in healthy subjects. This may be linked to higher serum concentrations of n-3 fatty acids, which promote a favorable composition of phospholipids.
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4.
  • Andersson, Irene, 1978, et al. (författare)
  • Endothelial dysfunction in growth hormone transgenic mice
  • 2006
  • Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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5.
  • Andersson, Irene, 1978, et al. (författare)
  • Increased atherosclerotic lesion area in apoE deficient mice overexpressing bovine growth hormone
  • 2006
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 188:2, s. 331-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Human growth hormone (GH) excess is linked to increased cardiovascular morbidity and mortality. However, little is known about the effect of GH excess on atherosclerosis. We developed a new mouse model to assess the hypothesis that GH overexpression accelerates atherosclerotic lesion formation. apoE(-/-) mice were crossed with bovine GH (bGH) transgenic mice to yield apoE(-/-) mice overexpressing bGH (apoE(-/-)/bGH). The mice were fed either standard or Western diet. At 22 weeks, atherosclerotic lesion area of thoracic aorta was larger in apoE(-/-)/bGH mice compared with littermate apoE(-/-) mice fed either diet (standard: +161+/-50%, Western: +430+/-134%). Aortic sinus lesions were more severe in apoE(-/-)/bGH mice fed standard diet compared with littermate apoE(-/-) mice. apoE(-/-)/bGH mice had lower (VLDL+LDL)/HDL ratios compared with littermate apoE(-/-) mice, while systolic blood pressure was higher in apoE(-/-)/bGH mice, irrespective of diet. The levels of serum amyloid A and hepatic CRP mRNA were higher in apoE(-/-)/bGH mice than in littermate apoE(-/-) mice. In conclusion, this study shows that excess GH augments the development of atherosclerosis in apoE(-/-) mice. The mechanisms could be direct effects of GH on cellular processes in the vessel wall or the result of concomitant processes such as hypertension or a general inflammatory state.
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6.
  • Anttila, V., et al. (författare)
  • Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
  • 2023
  • Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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7.
  • Anttila, V., et al. (författare)
  • Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
  • 2020
  • Ingår i: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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8.
  • Bernberg, Evelina, 1981, et al. (författare)
  • Effects of social isolation and environmental enrichment on atherosclerosis in ApoE-/- mice
  • 2008
  • Ingår i: Stress. - 1607-8888 .- 1025-3890. ; 11:5, s. 381-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Social support and a stimulating environment have been suggested to reduce stress reactions and cardiovascular risk. The aim of this study was to assess the role of environmental enrichment and social interaction for development of atherosclerosis in atherosclerosis prone mice. Male ApoE-/- mice were divided into four groups and followed during 20 weeks: (i) enriched environment (E, n=12), (ii) deprived environment (ED, n=12), (iii) enriched environment with exercise (E-Ex, n=12) and (iv) socially deprived by individual housing (SD, n=10). Plasma lipid and cytokine concentrations were measured. Atherosclerosis was quantified in cross-sections of innominate artery and en face in thoracic aorta. Plaque area was significantly increased in SD mice in the innominate artery (P<0.05 vs. all other groups), but not in the thoracic aorta. Plasma lipids were increased in SD mice (P<0.001 vs. all for total cholesterol, P<0.05 vs. E and P<0.01 vs. ED for triglycerides). Plasma concentration of granulocyte-colony stimulating factor (G-CSF) was decreased in SD mice compared to E mice (P<0.05). Thus, social isolation increased atherosclerosis and plasma lipids in ApoE-/- mice. Reduction in plasma G-CSF levels may hamper endothelial regeneration in the atherosclerotic process. While environmental enrichment did not affect atherosclerosis, social isolation accelerated atherosclerosis.
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9.
  • Blomster, Juuso I., et al. (författare)
  • Coronary flow reserve as a link between exercise capacity, cardiac systolic and diastolic function
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 217, s. 161-166
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Decreased coronary flow reserve (CFR) is associated with increased risk of adverse cardiovascular events. We sought to investigate how CFR from left anterior descending (LAD) coronary artery reflects clinical markers of cardiac function. Methods: We enrolled 400 patients referred for myocardium perfusion scintigraphy due to chest pain at Sahlgrenska University Hospital in Gothenburg, Sweden. Transthoracic echocardiography including adenosine-assisted CFR in LAD was performed at a separate occasion. Results: Median age was 62 years (range 32-83) and 47% were female. Prior myocardial infarction had occurred in 28% of the population. In adjusted multivariate models, CFR in LAD was associated with echocardiography left ventricle ejection fraction at rest (beta = 0.97, p = 0.033) as well as under stress (beta = 1.52, p = 0.0056) and maximum exercise capacity (beta = 6.27, p = 0.026). CFR in LAD outweighed left ventricle ejection fraction as the determinant of maximum exercise capacity. Hyperaemic diastolic mitral annulus peak velocity measured by vector velocity imaging was inversely associated with LAD CFR (beta = -0.39, p = 0.0077). In subgroup analyses these findings were associated with normal coronary perfusion in myocardium perfusion scintigraphy. Conclusions: In patients with angina-like symptoms CFR measured in LAD reflects well both systolic and diastolic cardiac function emphasizing the essential role of myocardial microvascular circulation in cardiac physiology. (C) 2016 Published by Elsevier Ireland Ltd.
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10.
  • Bryl-Górecka, Paulina, et al. (författare)
  • Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease.
  • 2021
  • Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:5, s. H2147-H2160
  • Tidskriftsartikel (refereegranskat)abstract
    • High levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. Plasma MVs were captured with acoustic trapping. Platelet and endothelial-derived MVs were measured with flow cytometry and MV lysates were analyzed with proteomic panels against cardiovascular biomarkers. Flow cytometry was further applied to identify cellular origin of biomarkers. Our data shows a negative correlation between MV concentration and CFR values. Platelet and endothelial MV levels were significantly increased in plasma from the low CFR group. CFR negatively correlates with the levels of several proteomic biomarkers and the low CFR group exhibited higher concentrations of these proteins in MVs. Focused analysis of one of the MV proteins, B Cell Activating Factor (BAFF), revealed platelet and not leukocyte origin and release upon proinflammatory stimulus. Higher levels of MVs carrying an elevated concentration of proatherogenic proteins, circulate in plasma in patients with low CFR, a marker of vascular dysfunction, reduced blood flow and poor prognosis. Our findings demonstrate a potential clinical value of MVs as biomarkers and possible therapeutic targets against endothelial deterioration.
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