| 1. |
- Fagerberg, Björn, 1943, et al.
(författare)
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Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques
- 2010
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Ingår i: Journal of Vascular Surgery. - 1423-0135. ; 47:3, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- Background: The heterogeneous structure of carotid atherosclerotic plaques may be better understood if it is related to blood flow variations, influencing gene expression and cellular functions. Upstream of the maximum stenosis there is laminar blood flow and high shear stress, downstream there is turbulence and low shear stress. We studied if these variations were associated with differences in plaque morphology and composition between sites located up- and downstream of the maximum stenosis in symptomatic carotid plaques. Methods: Patients with symptomatic carotid stenosis were examined with magnetic resonance angiography to localize the maximum stenosis in-vivo, prior to endarterectomy. In 41 endarterectomized specimens, transverse tissue sections prepared up- and downstream of the maximum stenosis were compared using histopathology and immunohistochemistry. Results: The location of maximum stenosis relative the carotid bifurcation varied considerably between plaques. Compared with the downstream side, the upstream side of the stenosis had higher incidence of severe lesions with cap rupture and intraplaque hemorrhage, more macrophages, less smooth muscle cells and more collagen. Conclusions: The up- and downstream sides of symptomatic carotid plaques differed in plaque morphology and composition. This implies that the intraplaque location of sampling sites may be a confounding factor in studies of atherosclerotic plaques.
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| 2. |
- Bergman, Olle, 1978, et al.
(författare)
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PITX3 polymorphism is associated with early onset Parkinson's disease.
- 2010
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:1, s. 114-117
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Tidskriftsartikel (refereegranskat)abstract
- PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p=0.002) or to PD patients with late onset (p=0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated.
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| 3. |
- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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15-Lipoxygenase-2 is expressed in macrophages in human carotid plaques and regulated by hypoxia-inducible factor-1 alpha
- 2010
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 1365-2362 .- 0014-2972. ; 40:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background Macrophages are prominent in hypoxic areas of atherosclerotic lesions and their secreted cytokines, growth factors and activity of enzymes are involved in atherogenesis. Previously, we showed that 15-lipoxygenase (LOX)-2 is expressed in human monocyte-derived macrophages and that hypoxia increases 15-LOX-2 expression and secretion of pro-inflammatory molecules. Here we investigated whether human carotid plaque macrophages express 15-LOX-2 and whether its expression in macrophages is regulated by hypoxia through hypoxia-inducible factor 1α (HIF-1α). Materials and methods Carotid plaques from 47 patients with high-grade symptomatic carotid artery stenosis were analysed using immunohistochemistry, and stained areas were quantified by digital image analysis. Carotid plaque macrophages were isolated with anti-CD14 immunobeads using an immunomagnetic bead technique. Primary macrophages were transfected with HIF-1α siRNA or control siRNA before extraction of RNA and medium analysis. Results In paired tissue sections, the extent of staining for CD68 correlated with staining for 15-LOX-2 but not for 15-LOX-1. In carotid plaque macrophages isolated with anti-CD14 immunobeads, 15-LOX-2 mRNA was expressed at high levels. In primary macrophages, 15-LOX-2 expression was significantly increased by incubation with the HIF-1α stabilizer dimethyloxalylglycine. Knockdown of HIF-1α significantly decreased production of the 15-LOX-2 enzyme products 12- and 15-hydroxyeicosatetraenoic acid. In carotid plaques, HIF-1α staining correlated with staining for 15-LOX-2. Conclusions These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1α. 15-LOX-2 enzyme activity can be modulated by HIF-1α. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.
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| 4. |
- Westerlund, Marie, et al.
(författare)
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Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease.
- 2011
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 25:4, s. 1345-52
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Tidskriftsartikel (refereegranskat)abstract
- The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.
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