PubMed Health⌕ Search

Biomedical subjects

Ryo Suzuki

Publications and source records attributed to Ryo Suzuki.

42 records · Page 3Linked to original sources
PubMed2002

Effect of AT2 receptor on expression of AT1 and TGF-beta receptors in VSMCs from SHR.

We recently reported that overexpression of the angiotensin II type 2 (AT2) receptor downregulates the AT1a receptor through the bradykinin/NO pathway in a ligand-independent manner in vascular smooth muscle cells (VSMCs). In the present study, we investigated the effect of AT2 receptor overexpression on the expression of the AT1a receptor and transforming growth factor-beta (TGF-beta) receptor subtypes in VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Transfection of the AT2 receptor gene downregulated expression of the AT1a receptor in VSMCs from WKY, but did not affect expression of the AT1a receptor in VSMCs from SHR. Transfection of the AT2 receptor abolished DNA synthesis in response to angiotensin II in VSMCs from WKY; in VSMCs from SHR, basal DNA synthesis was suppressed, but DNA synthesis in response to Ang II was not altered. The NO substrate L-arginine augmented downregulation of the AT1a receptor in VSMCs from WKY, whereas it did not affect expression of the AT1a receptor in VSMCs from SHR. In response to AT2 receptor transfection, expression of TGF-beta type I receptor mRNA was suppressed significantly in VSMCs from WKY, whereas expression of TGF-beta type I receptor was not altered in VSMCs from SHR. These results suggest that the AT2 receptor downregulates AT1a and TGF-beta type I receptors in normal VSMCs, but not in SHR-derived VSMCs. The lack of downregulation of the AT1a receptor may contribute, in part, to the exaggerated growth of VSMCs from SHR.

Activin Receptors, Type I↗
PubMed2002

Novel mechanisms of the antiproliferative effects of amlodipine in vascular smooth muscle cells from spontaneously hypertensive rats.

The calcium channel blocker amlodipine continues to be of interest due to its potential proven ability to hinder the progression of atherosclerosis and reduce the number of clinical ischemic events. Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) are useful in the study of atherosclerosis because they show exaggerated growth with production of angiotensin II (Ang II) by conversion to the synthetic phenotype. To clarify mechanisms of the antiproliferative effects of amlodipine, we evaluated effects of the expression of growth factors, the changes in phenotype, and the proliferation of VSMC from SHR. Amlodipine significantly inhibited basal DNA synthesis and proliferation of VSMC from SHR. Amlodipine also inhibited expression of platelet-derived growth factor (PDGF) A-chain, transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) mRNAs in VSMC from SHR. Decreases in levels of PDGF A-chain and bFGF mRNAs in VSMC from SHR were greater with amlodipine than with nifedipine. Amlodipine significantly inhibited expression of the synthetic phenotype markers osteopontin and matrix Gla mRNAs, indicating that it inhibited the exaggerated growth of VSMC from SHR and suppressed the change from the contractile phenotype to the synthetic phenotype. Thus, amlodipine may be a beneficial therapeutic agent for patients with hypertensive vascular diseases.

Amlodipine↗
PubMed2002

Transforming growth factor-beta expression in cardiovascular organs in stroke-prone spontaneously hypertensive rats with the development of hypertension.

Transforming growth factor (TGF)-beta activity is involved in several cardiovascular diseases owing to its effects on the growth of vascular smooth muscle cells and induction of extracellular matrix formation. We evaluated expression of TGF-beta in cardiovascular organs from stroke-prone spontaneously hypertensive rats (SHR-SP) which show severe cardiovascular damages with the development of hypertension. Twelve-week-old Wistar-Kyoto (WKY)/Izm rats and SHR-SP/Izm were loaded with 1% salt for 4 weeks. Aorta, heart and kidney were removed and evaluated histologically by hematoxylin-eosin staining. Expression of TGF-beta1 mRNA was evaluated by reverse transcription and polymerase chain reaction analysis in mRNA extracted with oligo dT-cellulose. Expression of TGF-beta1 protein was evaluated by Western blot analysis and immunohistochemical study in renal cortex. Whereas expression of TGF-beta1 mRNA was detected only in the heart of SHR-SP before salt loading, it was detected in the aorta, left ventricle of heart and renal cortex from both rat strains, and it was stronger in the renal cortex of SHR-SP than in the renal cortex of WKY rats. Expression of TGF-beta1 protein was markedly higher in the renal cortex of SHR-SP than in the renal cortex of WKY rats after salt loading. TGF-beta was localized at glomeruli and capillary arteries in the renal cortex, and immunostaining was stronger in SHR-SP than in WKY rats. Expression of TGF-beta1 was increased in glomeruli and capillaries of the renal cortex with the development of hypertension in SHR-SP. These results implicate TGF-beta in the renal damage observed in hypertension.

Animals↗
PubMed2002

Development of a novel cytomedical treatment that can protect entrapped cells from host humoral immunity.

Cell therapy is expected to relieve the shortage of donors needed for organ transplantation. When patients are treated with allogeneic or xenogeneic cells, it is necessary to develop a means by which to isolate administered cells from an immune attack by the host. We have developed "cytomedicine," which consists of functional cells entrapped in semipermeable polymer, and previously reported that alginate-poly-L-lysine-alginate microcapsules and agarose microbeads could protect the entrapped cells from injury by cellular immunity. However, their ability to isolate from humoral immunity was insufficient. It is well known that the complement system plays an essential role in rejection of transplanted cells by host humoral immunity. Therefore, the goal of the present study was to develop a novel cytomedical device containing a polymer capable of inactivating complement. In the screening of various polymers, polyvinyl sulfate (PVS) exhibited high anticomplement activity and low cytotoxicity. Murine pancreatic beta-cell line (MIN6 cell) entrapped in agarose microbeads containing PVS maintained viability and physiological insulin secretion, replying in response to glucose concentration, and resisted rabbit antisera in vitro. PVS inhibited hemolysis of sensitized sheep erythrocytes (EAs) and rabbit erythrocytes by the complement system. This result suggests that PVS inhibits both the classical and alternative complement pathways of the complement system. Next, the manner in which PVS exerts its effects on complement components was examined. PVS was found to inhibit generation of C4a and Ba generation in activation of the classical and alternative pathways, respectively. Moreover, when the EAC1 cells, which were carrying C1 on the EAs, treated with PVS were exposed to C1-deficient serum, hemolysis decreased in a PVS dose-dependent manner. These results suggest that PVS inhibits C1 in the classical pathway and C3 convertase formation in the alternative pathway. Therefore, PVS may be a useful polymer for developing an anticomplement device for cytomedical therapy.

Alginates↗
PubMedDate not supplied

Dendritic cells that endocytosed antigen-containing IgG-liposomes elicit effective antitumor immunity.

Liposomes represent a promising vehicle to deliver exogenous antigens to dendritic cells (DCs) for tumor immunotherapy. Targeting exogenous antigens to Fcgamma receptors on DCs has been shown to result in efficient presentation of antigen-derived peptides on major histocompatibility complex (MHC) class I and class II molecules. In this study, it was investigated whether DCs that endocytosed physicochemically optimized antigen-containing liposomes conjugated with IgG efficiently present antigens on MHC class I and class II molecules, and consequently induce strong antitumor immune responses. IgG-conjugated liposomes that were 200 nm in diameter without attaching polyethylene glycol were most efficiently endocytosed by DCs. Human monocyte-derived DCs that endocytosed tetanus toxoid (TT)-containing IgG liposomes via CD32 stimulated CD4(+) T cells more strongly than DCs pulsed with TT-containing bare liposomes or with soluble TT. Immunization of mice with DCs that endocytosed ovalbumin (OVA)-containing IgG liposomes but not OVA-containing bare liposomes or soluble OVA completely prevented the growth of OVA-expressing lymphoma cells. Importantly, administration of DCs that endocytosed OVA-containing IgG liposomes to the mice with established OVA-expressing tumors strongly suppressed tumor growth. This study demonstrates an IgG liposome with physicochemical properties suitable for delivering antigens to DCs and paves the way to the application of IgG liposomes for tumor immunotherapy using DCs.

Animals↗