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- Blomgren, Lena, 1957-, et al.
(författare)
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A comparison of magnetic resonance venography findings and venous occlusion plethysmography variables in postthrombotic syndrome
- 2017
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Ingår i: Vascular. - : Royal Society of Medicine Press. - 1708-5381 .- 1708-539X. ; 25:4, s. 406-411
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The relation between venous morphology and venous function in postthrombotic syndrome is poorly understood. The aim of this study was to compare obstruction and collateralization as seen with magnetic resonance venography with variables of venous occlusion plethysmography in patients with postthrombotic syndrome.Methods: Medical records, magnetic resonance venography and venous occlusion plethysmography data were analyzed in 28 patients (33 legs). Magnetic resonance venography images were scored for degree of obstruction and collateralization in segments of pelvic and abdominal veins and correlated to venous occlusion plethysmography data.Results: Obstruction of the inferior vena cava correlated with an overall increase of collaterals ( p < 0.001). The summary scores of collaterals or obstructions did not correlate with venous occlusion plethysmography variables. Relative expelled volume at 4 s correlated inversely with obstruction of the inferior vena cava ( p = 0.045) and vertebral collateralization ( p = 0.033).Conclusions: Modest correlations were found between magnetic resonance venography scores and venous occlusion plethysmography variables. Prospective studies with refined scoring and magnetic resonance venography techniques may increase our knowledge further.
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- Hägg, Sara, 1977-, et al.
(författare)
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Carbon-14 Dating to Determine Carotid Plaque Age : Carbon-14 Dating of Carotid Plaques
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rationale: The exact nature of atherosclerotic plaque development and the molecular mechanisms that lead to clinical manifestations of carotid stenosis are unclear. After nuclear bomb tests in the 1950s, atmospheric 14C concentrations rapidly increased. Since then, the concentrations have been declining, and the curve of declination can be used to date biological samples synthesized during the last five to six decades. Objective: To investigate plaque age as a novel characteristic of atherosclerotic plaques in patients with carotid stenosis. Methods and Results: Carotid plaques from 29 well-characterized endarterectomy patients with symptomatic carotid stenosis were analyzed by accelerator mass spectrometry, and global gene expression of 25 plaque samples was profiled with HG-U133 Plus 2.0 arrays. The average plaque age was 9.3 years, and inter- and intrasample standard variations were low (1–3.5 years); thus, most of the plaques were generated 5–15 years before surgery. Plaque age was not associated with patient age or plaque size, determined by intima-media thickness, but was inversely related to plasma insulin levels (P=0.0014). A cluster of functionally related genes enriched with genes involved in immune responses was activated in plaques with low plaque age, as were oxidative phosphorylation genes. Conclusion: Patients with mild insulin resistance have increased immune and inflammatory gene activity in their carotid plaques causing them to become instable, rapidly progressing into clinical manifestations at a relatively young age. These results show that plaque age, determined by 14C dating, is a novel and important characteristic of atherosclerotic plaques that will improve our understanding of the clinical significance and molecular underpinnings of atherosclerosis.
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- Hägg, Sara, et al.
(författare)
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Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4, s. e18248-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric C-14-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques. Methodology/Principal Finding: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for C-14 content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6+/-3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p=0.0014). Most plaques were echo-lucent rather than echo-rich (2.2460.97, range 1-5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8+/-12.4 vs. 50.4+/-6.2, p=0.00005; 57.6+/-26.1 vs. 39.8+/-25.7, p<0.0005, respectively), less collagen (45.3+/-6.1 vs. 51.1+/-9.8, p<0.05), and fewer smooth muscle cells (130+/-31 vs. 141+/-21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation. Conclusions/Significance: Our results show, for the first time, that plaque age, as judge by relative incorporation of C-14, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.
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- Hägg, Sara, 1977-, et al.
(författare)
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Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2 : The Stockholm Atherosclerosis Gene Expression (STAGE) Study
- 2009
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Ingår i: PLoS Genetics. - : PLoS Genetics. - 1553-7390 .- 1553-7404. ; 5:12, s. e1000754-
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n=66/tissue) and atherosclerotic and unaffected arterial wall (n=40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n=15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n=3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n=49/48) and one visceral fat (n=59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P=0.008 and P=0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n=55/54) relating to carotid stenosis (P=0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n=16/17, P<10-27and-30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, cellular and lesion expression of LDB2, and the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and together with LDB2 merits further attention in CAD research.
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- Rosfors, Stefan, et al.
(författare)
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Venous occlusion plethysmography in patients with post-thrombotic venous claudication
- 2013
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 58:3, s. 722-726
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Post-thrombotic venous claudication is a serious condition that may be treated with iliac vein stenting or open surgery, and there is a need for hemodynamic tests in the preoperative evaluation. The purpose of this study was to describe the results of venous occlusion plethysmography in patients with venous claudication and to analyze the outflow curve to find variables that best describe the functional abnormality in this patient group.METHODS: Twenty-nine patients with previous deep venous thrombosis and with clinical evidence of venous claudication were retrospectively identified. The results of venous occlusion plethysmography in these patients were compared with results obtained in a group of 63 healthy control subjects of similar age and sex. Computerized strain-gauge plethysmography was used in a capacitance mode where the occlusion time is determined by an electronic detector allowing the maximal venous volume to be achieved in all limbs. Outflow volumes (OV1, OV4) and outflow fractions (OF1, OF4) were calculated at 1 and 4 seconds after cuff release. Outflow fraction is OV divided by maximal venous volume.RESULTS: Both outflow volumes and outflow fractions were significantly reduced in patients compared with healthy control subjects. Outflow fractions were more sensitive than outflow volumes in identifying patients with venous claudication. The most discriminating variable was OF4 that was reduced below the normal lower limit in 69% of the patients, most severely reduced in patients with severe claudication.CONCLUSIONS: Patients with venous claudication attributable to remaining post-thrombotic iliofemoral obstructive disease are characterized by a functional disturbance shown with venous occlusion plethysmography as a reduced venous outflow during the initial 4 seconds following cuff release in relation to their true maximal venous volume. Our results suggest that venous occlusion plethysmography can be a valuable tool in the preoperative workup for selection of patients with iliofemoral vein obstruction that may benefit from venous intervention.
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- Skogsberg, Josefin, et al.
(författare)
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Whole-genome expression profiling of human plaques to identify genes relevant for atherosclerosis : the Stockholm Atherosclerosis Gene Expression Study, Stockholm Söder Hospital, Sweden (SöS-STAGE)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ObjectiveTo reveal relevant genes for atherosclerosis by whole-genome expression analyses of plaques from patients undergoing carotid endorectomy.Methods and ResultsWhole-genome expression measurements (WGEM) using Affymetrix HG-U133_Plus_2 chip of carotid plaques in patients undergoing carotid endorectomy at Stockholm Söder Hospital, Sweden. Patients were screened for conventional risk factors at a three-month follow-up visit and atherosclerosis burden in the common carotid artery (CCA) was measured by intima-media thickness (IMT). An unsupervised coupled two-way clustering approach identified genderspecific genes and 55 genes associated to degree of IMT in these patients.ConclusionsCoupled two-way clustering of carotid lesion expression profiles from a well-characterized clinical cohort is useful for identification of novel genes that may be relevant for atheroscleroris.
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