| 1. |
- Tukiainen, T., et al.
(författare)
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Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses
- 2012
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 16:7, s. 631-635
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Design: Longitudinal. Setting: City of Kuopio, Finland. Participants: 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. Measurement: On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via 1H NMR from native serum samples. Results: Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. Conclusion: These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline.
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| 2. |
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| 3. |
- Frye, Maike, et al.
(författare)
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Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development.
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| 4. |
- Lepäntalo, M., et al.
(författare)
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PTFE bypass or thrupass for superficial femoral artery occlusion? : A randomised controlled trial
- 2009
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 37:5, s. 578-584
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Tidskriftsartikel (refereegranskat)abstract
- Early results of a thrupass endograft in the treatment of femoral lesions are promising. Less morbidity and better cost-effectiveness are suggested to be achieved in the treatment of chronic lower limb ischaemia with endovascular treatment compared to surgical treatment. PATIENTS AND METHODS: This randomised multicentre trial aimed to enroll a group of 60+60 patients for the treatment of 5-25-cm occlusions of superficial femoral artery (SFA) to be followed up for 3 years. Patients were treated either with endoluminal PTFE thrupass (WL Gore & Ass) or with surgical polytetrafluoroethylene (PTFE) bypass to proximal popliteal artery. Primary patency at 3 years was scheduled to be the primary end-point and secondary patency, functional success, costs and quality of life the secondary end-points. RESULTS: A sample of 100 consecutive SFA occlusions in one of the centres revealed that only 4% of the lesions were amenable for the study. The trial was prematurely terminated due to the results of an interim analysis at the time when 44 patients were recruited: the 1-year primary patency (excluding technical failures) was 48% for thrupass and 95% for bypass (p=0.02). The patency difference in favour of surgical bypass over endovascular thrupass was also sustained after completion of 1-year follow-up, the primary patencies being 46% and 84% at 1 year with grossly equilinear life-table curves thereafter (p=0.18), respectively. The corresponding secondary patencies were 63% and 100% (p=0.05) when excluding technical failures and 58% and 100% (p=0.02) according to intention-to-treat analysis. Secondary outcomes were thus not analysed. CONCLUSION: Treatment of SFA occlusions (TASC IIB and C or Imelda Ia and II) should be done by PTFE bypass rather than by PTFE thrupass, as thrupass is connected with worse early outcome. These results represent only a small category of femoral disease.
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| 7. |
- Martin-Almedina, Silvia, et al.
(författare)
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EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis
- 2016
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 126:8, s. 3080-3088
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Tidskriftsartikel (refereegranskat)abstract
- Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate.
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| 8. |
- Nikitenko, Leonid L, et al.
(författare)
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Adrenomedullin haploinsufficiency predisposes to secondary lymphedema.
- 2013
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 133:7
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Tidskriftsartikel (refereegranskat)abstract
- Secondary lymphedema is a debilitating condition, and genetic factors predisposing to its development remain largely unknown. Adrenomedullin (AM) is peptide encoded, together with proadrenomedullin N-terminal peptide (PAMP), by the Adm gene (adrenomedullin gene). AM and its putative receptor calcitonin receptor-like receptor (CLR) are implicated in angiogenesis and lymphangiogenesis during embryogenesis and wound healing, suggesting their possible involvement in secondary lymphedema. To investigate whether AM deficiency predisposes to secondary lymphedema, we used heterozygous adult mice with Adm gene-knockin stop mutation, which selectively abrogated AM, but preserved PAMP, expression (Adm(AM+/Δ) animals). After hind limb skin incision, Adm messenger RNA expression was upregulated in wounded tissue of both Adm(AM+/+) and Adm(AM+/Δ) mice. However, only Adm(AM+/Δ) animals developed limb swelling and histopathological lymphedematous changes, including epidermal thickening, elevated collagen fiber density, and increased microvessel diameter. Secondary lymphedema was prevented when circulating AM levels in Adm(AM+/Δ) mice were restored by systemic peptide delivery. In human skin, CLR was expressed in tissue components affected by lymphedema, including epidermis, lymphatics, and blood vessels. Our study identified a previously unrecognized role for endogenous AM as a key factor in secondary lymphedema pathogenesis and provided experimental in vivo evidence of an underlying germ-line genetic predisposition to developing this disorder.
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| 9. |
- Petrova, Tatiana V, et al.
(författare)
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Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor.
- 2002
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Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 21:17
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Tidskriftsartikel (refereegranskat)abstract
- Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of approximately 40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.
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