Biomedical subjects

Atsushi Shioi

Publications and source records attributed to Atsushi Shioi.

22 records · Page 2Linked to original sources

PubMed2002

Thrombospondin-1 mediates smooth muscle cell proliferation induced by interaction with human platelets.

OBJECTIVES: Platelet adherence and activation are associated with smooth muscle cell (SMC) proliferation and arterial restenosis. This study examined platelet-SMC interaction on fibrillar type I collagen and analyzed the role of thrombospondin (TSP)-1 in platelet-induced SMC proliferation. METHODS AND RESULTS: When SMCs cultured on fibrillar collagen were treated with human platelets (5 preparations), 7.45+/-2.94% of the cells passed through S phase within 24 hours, as determined by bromodeoxyuridine nuclear labeling. The addition of platelets markedly induced SMC TSP-1 mRNA expression and cell surface protein accumulation, which colocalized with adhered platelets, as determined by alpha(IIb) integrin immunostaining. Direct interaction of platelets with SMCs was necessary for its effect on proliferation and TSP-1 accumulation, as determined in the transwell culture system. The anti-TSP-1 blocking antibody strongly inhibited platelet-induced SMC proliferation by approximately 60%. Analysis of the receptors for TSP-1 accumulation on the SMC surface revealed that beta1 integrins are mainly involved. The anti-beta1 integrin blocking antibody, which potently suppressed TSP-1 accumulation on SMCs, also markedly inhibited platelet-stimulated SMC proliferation. CONCLUSIONS: TSP-1 and beta1 integrin interaction is involved in platelet-stimulated SMC proliferation. This in vitro coculture system could prove useful for examining the molecular mechanism underlying platelet-induced vascular remodeling and for studying the mechanism of a tested drug for restenosis.

Arteriosclerosis↗

PubMed2002

Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells: roles of tumor necrosis factor-alpha and oncostatin M derived from macrophages.

Inflammatory cells such as macrophages and T lymphocytes play an important role in vascular calcification associated with atherosclerosis and cardiac valvular disease. In particular, macrophages activated with cytokines derived from T lymphocytes such as interferon-gamma (IFN-gamma) may contribute to the development of vascular calcification. Moreover, we have shown the stimulatory effect of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on in vitro calcification through increasing the expression of alkaline phosphatase (ALP), an ectoenzyme indispensable for bone mineralization, in vascular smooth muscle cells. Therefore, we hypothesized that macrophages may induce calcifying phenotype, especially the expression of ALP in human vascular smooth muscle cells (HVSMCs) in the presence of IFN-gamma and 1,25(OH)2D3. To test this hypothesis, we used cocultures of HVSMCs with human monocytic cell line (THP-1) or peripheral blood monocytes (PBMCs) in the presence of IFN-gamma and 1,25(OH)2D3. THP-1 cells or PBMCs induced ALP activity and its gene expression in HVSMCs and the cells with high expression of ALP calcified their extracellular matrix by the addition of beta-glycerophosphate. Thermostability and immunoassay showed that ALP induced in HVSMCs was bone-specific enzyme. We further identified tumor necrosis factor-alpha (TNF-alpha) and oncostatin M (OSM) as major factors inducing ALP in HVSMCs in the culture supernatants of THP-1 cells. TNF-alpha and OSM, only when applied together, increased ALP activities and in vitro calcification in HVSMCs in the presence of IFN-gamma and 1,25(OH)2D3. These results suggest that macrophages may contribute to the development of vascular calcification through producing various inflammatory mediators, especially TNF-alpha and OSM.

Alkaline Phosphatase↗

PubMed2002

[Strategies for researches on the interactions between skeletal and vascular tissues].

Osteoporosis and vascular disease are commonly found together in estrogen-deficient and elderly people. The common factors such as estrogen deficiency, abnormalities of vitamin D metabolism, and lipid oxidation have been suggested to contribute to the development of osteoporosis and atherosclerosis. Recent research works on the mechanism of arterial calcification using in vitro models and mouse genetics have unraveled the potential molecular link between osteoporosis and arterial calcification.

English Abstract↗

PubMed2002

[Mechanism of vascular calcification].

Vascular calcification is an active, regulated process rather than a passive accumulation of mineral in areas of necrosis or injury including atherosclerotic plaque, aging, or damaged cardiac valves. This review describes roles of the following factors in progression of vascular calcification: (1)apoptotic cell death or chondro/osteogenic differentiation of vascular mesenchymal cells, (2)sodium-dependent phosphate co-transporter, (3)alkaline phosphatase and nucleotide triphosphate pyrophosphohydrolase (metabolism of inorganic pyrophosphate), (4)inflammatory cells such as T cells and macrophages, (5)regulatory factors including hormones, growth factors, and cytokines.

English Abstract↗