| 1. |
- Turczynska, Karolina, et al.
(författare)
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Regulation of Smooth Muscle Dystrophin and Synaptopodin 2 Expression by Actin Polymerization and Vascular Injury.
- 2015
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 35:6, s. 1489-1497
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Tidskriftsartikel (refereegranskat)abstract
- Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype.
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| 2. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 3. |
- Mokhtari, Arash, et al.
(författare)
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Haemodynamic effects of -75 mmHg negative pressure therapy in a porcine sternotomy wound model.
- 2009
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Ingår i: International Wound Journal. - 1742-481X. ; 6:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown -125 mmHg to be the optimal negative pressure for creating an environment that promotes wound healing, and this has therefore been adopted as a standard pressure for patients with deep sternal wound infection. However, it has not yet been clearly shown that -125 mmHg is the optimal pressure from a haemodynamic point of view. Furthermore, there have been reports of cardiac rupture during -125 mmHg negative pressure therapy. We therefore studied the effects of a lower pressure: -75 mmHg. Twelve pigs were used. After median sternotomy, sealed negative pressure therapy of -75 mmHg was applied. Baseline measurements were made and continuous recording of the cardiac output, end-tidal CO(2) production, mean arterial pressure, mean pulmonary pressure (pulmonary artery pressure), systemic vascular resistance, pulmonary vascular resistance, left atrial pressure and central venous pressure was started. Six pigs served as controls. No statistically significant difference was observed in any of the haemodynamic parameters studied, compared with the controls. The present study shows that, with a suitable foam application technique, -75 mmHg can be applied without compromising the central haemodynamics.
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| 4. |
- Mokhtari, Arash, et al.
(författare)
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The cost of vacuum-assisted closure therapy in treatment of deep sternal wound infection.
- 2008
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 42:1, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Surgical sites infections are very expensive and the total costs for coronary artery bypass grafting (CABG) surgery followed by deep sternal wound infection (DSWI) with conventional therapy are estimated to be 2.8 times that for normal, CABG surgery. Promising results have been reported with vacuum-assisted closure (VAC) therapy in patients with DSWI. This study presents the cost of VAC therapy in patients with DSWI after CABG surgery. Design. Thirty-eight CABG patients with DSWI, between 2001 and 2005, were treated with VAC therapy. The cost of surgery, intensive care, ward care, laboratory tests and other costs were analyzed. Results. No three-month mortality or recurrent infection was observed. The average cost of CABG procedure and treatment of DSWI was 2.5 times higher than the mean cost of CABG alone. No significant correlations were found between the preoperative EuroSCORE and the cost of DSWI therapy. Conclusions. VAC therapy for patients who underwent CABG surgery followed by DSWI seems to be cost effective, and has low mortality rate.
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| 5. |
- Andersson, Peter, et al.
(författare)
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Anorexia Nervosa With Comorbid Severe Depression : A Systematic Scoping Review of Brain Stimulation Treatments
- 2023
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Ingår i: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 39:4, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.
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| 6. |
- Hien, Tran T., et al.
(författare)
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MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle
- 2018
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 233:9, s. 7195-7205
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.
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| 7. |
- Nozohoor, Shahab, et al.
(författare)
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B-Type Natriuretic Peptide as a Predictor of Postoperative Heart Failure After Aortic Valve Replacement.
- 2009
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 23, s. 161-165
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: B-type natriuretic peptide (BNP) has been established as a biomarker for heart failure. The objective was to evaluate BNP measured on arrival in the intensive care unit (ICU) as a predictor for heart failure defined as need for inotropic support or IABP beyond 24 hours postoperatively after aortic valve replacement. DESIGN: A prospective, observational study. SETTING: A cardiothoracic surgery unit at a tertiary level hospital. PARTICIPANTS: One hundred sixty-one patients undergoing aortic valve replacement. MEASUREMENTS AND MAIN RESULTS: Two levels of BNP were evaluated: the median (BNP >133 pg/mL) and a cutoff (BNP >82 pg/mL) based on receiver-operating characteristic (ROC) analysis. Uni- and multivariate analysis were performed to identify predictors of postoperative heart failure. Patients with postoperative heart failure (n = 37) showed a more than 10-fold increase in 30-day mortality (8.1%, 3/37) compared with patients without postoperative heart failure (0.8%, 1/124) (p = 0.038). Elevated postoperative BNP levels were identified as an independent predictor of postoperative heart failure: BNP >82 pg/mL (p = 0.004) and BNP >133 pg/mL (p = 0.013). The area under the ROC curve for BNP as a predictor of postoperative heart failure was 0.69. CONCLUSION: Postoperative heart failure after aortic valve replacement is still a very serious condition with increased early mortality. The results of the present study suggest that an elevated BNP level on arrival in the ICU is an independent predictor of postoperative heart failure after aortic valve replacement. In the authors' opinion, an increased BNP level on arrival in the ICU may support early diagnosis and allow optimal management of heart failure after aortic valve replacement.
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| 8. |
- Nozohoor, Shahab, et al.
(författare)
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Influence of prosthesis-patient mismatch on diastolic heart failure after aortic valve replacement.
- 2008
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 85:4, s. 1310-1318
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bioprostheses for supraannular placement have been developed to optimize the hemodynamic performance after aortic valve replacement. To evaluate the potential benefit of this design, we analyzed the influence of prosthesis-patient mismatch on diastolic function and left ventricular mass regression and evaluated the clinical performance of the Sorin Soprano and Medtronic Mosaic in the aortic position. METHODS: A total of 372 patients underwent aortic valve replacement between July 2004 and February 2007, receiving either a Sorin Soprano (n = 235) or a Medtronic Mosaic (n = 137) prosthetic valve. Echocardiographic and clinical data were collected prospectively, and follow-up was performed in April 2007. Multivariate analyses were used to identify differences in hemodynamic performance, diastolic function, left ventricular mass regression, and predictors of impaired survival. Kaplan-Meier survival curves and log-rank tests were used to compare postoperative outcomes. RESULTS: The 30-day mortality was 1.7% (4 of 235 patients) in the Sorin Soprano group and 2.9% (4 of 137 patients) in the Medtronic Mosaic group (p = 0.473). Neither prosthesis-patient mismatch nor type of prosthesis was a significant predictor of early or late mortality. Diastolic heart failure was a predictor of poor survival (p = 0.004); however, the recovery of diastolic function was not significantly influenced by prosthesis-patient mismatch. Neither moderate (indexed effective orifice area < 0.85 cm(2)/m(2)) nor severe (indexed effective orifice area < 0.65 cm(2)/m(2)) prosthesis-patient mismatch resulted in a significantly impaired left ventricular mass regression. CONCLUSIONS: Prosthesis-patient mismatch was not an independent predictor of poor survival, impaired left ventricular mass regression, or recovery of diastolic function. The Sorin Soprano and the Medtronic Mosaic bioprostheses demonstrated comparable hemodynamic performance and excellent clinical outcome without signs of structural valve deterioration during follow-up.
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| 9. |
- Nozohoor, Shahab, et al.
(författare)
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Influence of prosthesis-patient mismatch on left ventricular remodelling in severe aortic insufficiency.
- 2010
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940. ; 37, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The present study evaluates the impact of prosthesis-patient mismatch (PPM) on left ventricular remodelling following aortic valve replacement (AVR) for severe aortic insufficiency. Methods: In this study, 230 patients undergoing aortic valve surgery were divided into two groups depending on whether or not they exhibited PPM. Postoperative left ventricular (LV) dimensions and function were compared to the preoperative status. Results: The incidence of PPM (EOAi
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| 10. |
- Nozohoor, Shahab, et al.
(författare)
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Postoperative Increase in B-Type Natriuretic Peptide Levels Predicts Adverse Outcome After Cardiac Surgery.
- 2011
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; Okt, s. 469-475
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: To evaluate the prognostic implication of changes in postoperative B-type natriuretic peptide (BNP) concentrations in patients undergoing cardiopulmonary bypass for cardiac surgery. DESIGN:: A retrospective analysis of prospectively collected clinical data. SETTING:: Cardiothoracic surgery and an intensive care unit (ICU) in a university hospital. PARTICIPANTS:: The present study included a total of 407 consecutive patients undergoing cardiac surgery. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: BNP concentrations were measured on admittance to the ICU (D0) and at day 1 after surgery. Patients were divided into quintiles according to their BNP level on admittance to the ICU. The predictive value of absolute changes in BNP levels during the first 24 hours postoperatively was analyzed with Kaplan-Meier estimates of survival and Cox multivariate proportional analysis. Prognostic factors for impaired midterm survival included elevation of the BNP level (HR, 7.3/ log10(x); 95% confidence interval, 1.8-29, p = 0.005). The BNP levels of patients undergoing isolated valve surgery or valve and concomitant CABG surgery were significantly higher (p = 0.012 and p = 0.032, respectively) than those undergoing isolated coronary artery bypass graft surgery. Patients in higher quintiles required ventilation for a longer time (p < 0.001), and prolonged inotropic support (p < 0.001). The mean plasma BNP concentration of 172 pg/mL (median, 64; interquartile range, 172) on arrival at the ICU had a sensitivity of 75% and a specificity of 74% for predicting 1-year mortality. CONCLUSIONS:: Elevated BNP levels on admittance to the ICU and postoperatively increasing BNP levels are associated with adverse postoperative outcome and are predictive of impaired late survival. Sequential postoperative BNP monitoring facilitates the early identification of patients at an increased risk of heart failure and may be used as an adjunct for clinical decision making and optimized patient management.
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