Biomedical subjects

Mari Niemi

Publications and source records attributed to Mari Niemi.

3 recordsLinked to original sources

PubMed2002

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible endothelial cell mitogen and survival factor. Its receptor VEGFR-2 (KDR/Flk-1) mediates these effects. We studied the expression of VEGF and VEGFR-2 in ischemic human and rabbit skeletal muscle by immunohistochemistry and in situ hybridization. Human samples were obtained from eight lower limb amputations because of acute or chronic critical ischemia. In chronically ischemic human skeletal muscle VEGF and VEGFR-2 expression was restricted to atrophic and regenerating skeletal myocytes, whereas in acutely ischemic limbs VEGF and VEGFR-2 were expressed diffusely in the affected muscle. Hypoxia-inducible factor-1alpha was associated with VEGF and VEGFR-2 expression both in acute and chronic ischemia but not in regeneration. Hindlimb ischemia was induced in 20 New Zealand White rabbits by excising the femoral artery. Magnetic resonance imaging and histological sections revealed extensive ischemic damage in the thigh and leg muscles of ischemic rabbit hindlimbs with VEGF expression similar to acute human lower limb ischemia. After 1 and 3 weeks of ischemia VEGF expression was restricted to regenerating myotubes and by 6 weeks regeneration and expression of VEGF was diminished. VEGFR-2 expression was co-localized with VEGF expression in regenerating myotubes. Macrophages and an increased number of capillaries were associated with areas of ischemic muscle expressing VEGF and VEGFR-2. In conclusion, two patterns of VEGF and VEGFR-2 expression in human and rabbit ischemic skeletal muscle are demonstrated. In acute skeletal muscle ischemia VEGF and VEGFR-2 are expressed diffusely in the affected muscle. In chronic skeletal muscle ischemia and in skeletal muscle recovering from ischemia VEGF and VEGFR-2 expression are restricted to atrophic and regenerating muscle cells suggesting the operation of an autocrine pathway that may promote survival and regeneration of myocytes.

Aged↗

PubMed2002

Changes in gene expression in atherosclerotic plaques analyzed using DNA array.

A better understanding of atherogenesis at the level of gene expression could lead to the identification of new therapeutic strategies for vascular diseases. With DNA array technology, it is possible to identify multiple, simultaneous changes in gene expression in small tissue samples from atherosclerotic arteries. We analyzed gene expression in normal arteries and in immunohistologically characterized human advanced atherosclerotic lesions using an array of 18376 cDNA fragments. The array method was first validated by detecting a group of genes (n=17) that were already known to be connected to atherogenesis. These genes included e.g. Apolipoprotein E, CD68, TIMP and phospholipase D. Next we detected 75 differentially expressed genes that were previously not connected to atherogenesis. A subgroup of genes involved in cell signaling and proliferation was selected for further analyzes with in situ hybridization and RT-PCR which confirmed array results by showing induction in advanced lesions of Janus kinase 1 (JAK-1) which is an important signaling molecule in activated macrophages; VEGF receptor-2 which mediates angiogenic and vasculoprotective effects of VEGF; and an unknown gene, which mapped on chromosome 19. It is concluded that DNA array technology enables fast screening of gene expression in small samples of atherosclerotic lesions. The technique will be useful for the identification of new factors, such as JAK-1 and VEGF receptor-2, which may play an important role in atherogenesis.

Adult↗

PubMed2002

Apolipoprotein E and colon cancer. Expression in normal and malignant human intestine and effect on cultured human colonic adenocarcinoma cells.

Background: Apolipoprotein E (apo E) is a key regulatory protein in lipoprotein metabolism and it is also a potent inhibitor of cell proliferation. Although genetic alterations of apo E affect enterohepatic cholesterol transport and, presumably, the risk of colon carcinoma, the expression and potential functions of apo E in the human intestine are poorly known. Methods: The localization of apo E in normal and malignant gastrointestinal tract was studied using immunohistochemistry and in situ hybridization. The effect of apo E3 on cell polarity and the distribution of beta-catenin was examined in HT29 human colon adenocarcinoma cell lines. Results: Both apo E protein and mRNA were present throughout human intestine. The macrophages in the superficial lamina propria of normal colon were more strongly positive for apo E than those in the small intestine, where the most positively stained cells were dendritic cells and macrophages in the germinal centers of lymphoid follicles. In carcinomas, intensely positive macrophages surrounded the tumor area. In cultured undifferentiated HT29 cells, treatment with apo E improved cell polarity and translocated beta-catenin from the cytoplasm to cell--cell adhesion sites. Conclusions: Mononuclear phagocytes and endocrine cells are the main source of apo E in the gastrointestinal tract. We hypothesize that macrophage-derived apo E may modulate epithelial integrity and thus contribute to cell growth.

Journal Article↗