| 1. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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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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| 2. |
- Barres, R., et al.
(författare)
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Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density
- 2009
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 10:3, s. 189-98
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic modification through DNA methylation is implicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) in diabetic subjects. Methylation levels were negatively correlated with PGC-1alpha mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1alpha was found within non-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter.
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| 3. |
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| 4. |
- Bång, Angela, et al.
(författare)
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Lower mortality after prehospital recognition and treatment followed by fast tracking to coronary care compared with admittance via emergency department in patients with ST-elevation myocardial infarction.
- 2008
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 129:3, s. 325-332
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe the short-and long-term outcome among patients with an ST-elevation myocardial infarction (STEMI), assessed and treated by the emergency medical services (EMS) in relation to whether they were fast tracked to a coronary care unit (CCU) or admitted via the emergency department (ED). METHODS: Consecutive patients admitted to the CCU at Sahlgrenska University Hospital with ST elevations on admission ECG were analysed with respect to whether they by the EMS were fast tracked to the CCU or the adjacent coronary angiography laboratory (direct CCU group; n=261) or admitted via the ED (ED group; n=235). RESULTS: Whereas the two groups were similar with regard to age and previous history, those who were fast tracked to CCU were more frequently than the ED patients diagnosed and treated as STEMI already prior to hospital admission. Reperfusion therapy was more commonly applied in the CCU group compared with the ED group (90% vs 67%; <0.0001). The delay times (median) were shorter in the direct CCU group than in the ED group, with a difference of 10 min from the onset of symptoms to arrival in hospital and 25 min from hospital arrival to the start of reperfusion treatment (primary PCI or in-hospital fibrinolysis). Patients in the direct CCU group had lower 30-day mortality (7.3% vs. 15.3%; p=0.004), as well as late mortality (>30 days to five years) (11.6% vs. 20.6%; p=0.008). CONCLUSION: Among patients transported with ambulance due to STEMI there was a significant association between early recognition and treatment followed by fast tracking to the CCU and long term survival. A higher rate of and a more rapid revascularisation were probably of significant importance for the outcome.
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| 5. |
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| 6. |
- Gjertsson, Peter, 1961, et al.
(författare)
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Diagnostic and referral delay in patients with aortic stenosis is common and negatively affects outcome
- 2007
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Ingår i: Scand Cardiovasc J. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 41:1, s. 12-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Aortic stenosis (AS) patients are often severely symptomatic at the time of aortic valve replacement (AVR). We wanted to investigate doctors' delay and its impact on outcome. DESIGN: AS patients undergoing AVR (n = 422) were included. Clinical and echocardiographic data at the time of diagnosis and preoperatively were noted. The risk of death after AVR was estimated using Poisson regression, incorporating age, gender, coronary artery disease, NYHA III/IV and time on the waiting list for AVR. RESULTS: The age (mean+/-SD) was 71+/-8.6 years, 45% were women, and 48% were in NYHA III/IV. 55% underwent AVR within one year of diagnosis, indicating late diagnosis. The time from referral to AVR (median, range) was 112 (1-803) days. NYHA III/IV independently predicted mortality (hazard ratio 1.76, 95% CI 1.28-2.43, p = 0.0005). The time from referral to AVR influenced the risk of death immediately after operation (p = 0.0083). CONCLUSION: Late diagnosis and late referral for AVR are common, and negatively influence outcome in patients with AS. Delay in surgery after referral increase the mortality immediately after AVR.
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| 7. |
- Gjertsson, Peter, 1961, et al.
(författare)
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Left ventricular diastolic dysfunction late after aortic valve replacement in patients with aortic stenosis
- 2005
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Ingår i: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:5, s. 722-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with severe aortic stenosis (AS) are known to have increased left ventricular (LV) mass and diastolic dysfunction. It has been suggested that LV mass and diastolic function normalize after aortic valve replacement (AVR). In the present study, change in LV mass index and diastolic function 10 years after AVR for AS was evaluated. Patients who underwent AVR from 1991 to 1993 (n = 57; mean age 67 +/- 8.6 years at AVR, 58% men) were investigated with Doppler echocardiography preoperatively and 2 and 10 years postoperatively. Diastolic function was evaluated by integrating mitral and pulmonary venous flow data. Expected values for each patient, taking age into consideration, were defined using a control group (n = 71; age range 18 to 83 years). Patients were classified into 4 types: normal diastolic function (type A), mild diastolic dysfunction (type B), moderate diastolic dysfunction (type C), and severe diastolic dysfunction (type D). There was a reduction in LV mass index between the preoperative (161 +/- 39 g/m2) and 2-year follow-up (114 +/- 28 g/m2) examinations (p <0.0001), but no further reduction was seen at 10 years (119 +/- 49 g/m2). The percentage of patients with increased LV mass index decreased from 83% preoperatively to 29% at 2-year follow-up (p <0.001). The percentage of patients with moderate to severe LV diastolic dysfunction (types C and D) was unchanged between the preoperative (7%) and 2-year follow-up (13%) examinations (p = 0.27). The percentage of patients increased at 10-year follow-up to 61% (p <0.0001). In conclusion, this reveals the development of moderate to severe diastolic dysfunction 10 years after AVR, despite a reduction in the LV mass index.
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| 8. |
- Gjertsson, Peter, 1961, et al.
(författare)
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Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis
- 2005
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Ingår i: J Thorac Cardiovasc Surg. - : Elsevier BV. - 0022-5223. ; 129:4, s. 890-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We studied long-term outcomes in severe aortic stenosis and the importance of prosthesis type (mechanical vs biologic) and size, preoperative left ventricular ejection fraction, diastolic function, and left ventricular mass. METHODS: Patients undergoing valve replacement from 1991 to 1993 (n = 399, 45% women) were included. The diastolic function was evaluated by integrating mitral and pulmonary venous flow data with Doppler echocardiography. The patients were classified as having either normal diastolic function to mild diastolic dysfunction or moderate to severe diastolic dysfunction. Left ventricular ejection fraction and the diastolic function category were incorporated together with age, sex, and time since operation into a Poisson regression model with death as the end point. Prosthesis type and size and left ventricular mass were also investigated. RESULTS: The age (mean +/- SD) was 71 +/- 9 years, and the overall survival after 12 years was 50%. Although markedly reduced during the initial 6-month period, mortality risk subsequently increased more than could be explained by age (hazard ratio of 1-year difference = 1.12, P = .0005). The moderate to severe diastolic dysfunction pattern independently predicted late mortality (hazard ratio = 1.72, P = .0038), whereas left ventricular ejection fraction did not (hazard ratio = 0.99, P = .18). The prognostic importance of moderate to severe diastolic dysfunction did not diminish with time; on the contrary, it tended to increase. Mortality after 12 years was not predicted by left ventricular mass (P = .66), prosthesis type (P = .57), or prosthesis size (P = .58). CONCLUSION: This study reveals that moderate to severe diastolic dysfunction in patients with aortic stenosis is an independent predictor of late mortality after valve replacement and that its importance does not decrease with time. Our findings may suggest that moderate to severe diastolic dysfunction implies nonreversible myocardial changes that negatively affect survival.
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| 9. |
- Glund, S., et al.
(författare)
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Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1630-7
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, plasma IL-6 levels also increase during exercise, with skeletal muscle being the predominant source. Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P < 0.05). A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. IL-6 also increased skeletal muscle glucose incorporation into glycogen, as well as glucose oxidation (1.5- and 1.3-fold, respectively; P < 0.05). IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. In conclusion, acute IL-6 exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
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| 10. |
- Guron, Cecilia Wallentin, 1965, et al.
(författare)
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Can the left ventricular early diastolic tissue-to-blood time interval be used to identify a normal pulmonary capillary wedge pressure?
- 2007
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Ingår i: Eur J Echocardiogr. - : Oxford University Press (OUP). - 1525-2167. ; 8:2, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- The pulsed Doppler early diastolic left ventricular (LV) tissue (e)-blood (E) onset temporal relationship (e-E) is suggested to predict pulmonary capillary wedge pressure (PCWP), through the formulas: tau = 32 + 0.7(e-E) and PCWP = LV end-systolic pressure x e(-IVRT/tau). Small changes/errors in E could influence the quotient IVRT/tau by oppositely affecting IVRT and e-E. At rest in 50 healthy individuals we noted: e-E: 2 +/- 14 ms; IVRT: 89 +/- 17 ms; calculated tau: 33 +/- 10 ms; and PCWP: 9 +/- 9 mmHg (> 12 mmHg in 28%). Non-pharmacological preload alterations in 14 individuals rendered an intraindividual 'PCWP'-fluctuation of up to 40 mmHg. This application may therefore not be clinically robust.
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