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Biomedical subjects

H Doi

Publications and source records attributed to H Doi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Lysophosphatidylcholine induces urokinase-type plasminogen activator and its receptor in human macrophages partly through redox-sensitive pathway.

Urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPAR) have been shown to be expressed in macrophages in atherosclerotic arterial walls, but the regulatory mechanisms of their expression remain unclear. The present study was performed to examine the effects of lysophosphatidylcholine (lysoPC), an important atherogenic lipid, on the expression of uPA and uPAR in human monocyte-derived macrophages. LysoPC upregulated the mRNA expression of uPA and uPAR, and it increased the protein expression of uPA in the culture medium and bound to the cell surface and of uPAR in the particulate fraction of the cells. LysoPC significantly increased the binding of the amino-terminal fragment of uPA to the treated cells and the cell-associated plasminogen activator activity. LysoPC stimulated superoxide anion production and increased intracellular oxidant levels in the cells. The combined incubation with reduced glutathione diethyl ester or N-acetylcysteine, antioxidants, suppressed the upregulation of uPA and uPAR mRNA and the increase in plasminogen activator activity by lysoPC. uPA and uPAR mRNA expression was also induced by the incubation with xanthine and xanthine oxidase, a superoxide anion-generating system. The results suggest that lysoPC increased the expression of uPA and uPAR and their functional activities in human monocyte-derived macrophages, at least in part through a redox-sensitive mechanism. This coordinate increase in the expression of uPA and uPAR in human macrophages by lysoPC could play an important role in plaque formation and disruption, arterial remodeling, and angiogenesis in atherosclerotic arterial walls.

Acetylcysteine↗
PubMed2000

Super-elastic property of Ti-Ni alloy for use in dentistry.

The super-elasticity of Ti-Ni alloy was investigated in tensile and bending tests to evaluate the mechanical properties of the castings and heat treatment effect on the bending properties of the wires for new clinical applications of the alloy in prosthodontics and orthodontics. In terms of the tensile properties of the castings, apparent proof stress increased and elongation decreased with the small increase in nickel content or with the decrease in titanium purity. This result suggests that precise control of the materials is indispensable to utilize the super-elasticity in dental cast appliances. In terms of the bending properties of Ti-Ni alloy wires, low residual deflection and small load/deflection ratio were obtained by the second heat treatment between 733 and 813 K, which was found to be suitable for the shape memory treatment of orthodontic appliances. Moreover, the functional force was changeable within this treatment temperature range.

Biocompatible Materials↗
PubMed2000

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Animals↗
PubMed2000

Unclassified connective tissue disease presenting as cardiac tamponade: a case report.

This report describes a case of cardiac tamponade as the initial manifestation of unclassified connective tissue disease (UCTD). A 68-year-old Japanese woman was admitted to hospital because of dyspnea and edema. She had undergone a radical left mastectomy for the treatment of breast cancer 18 years before. On admission, bilateral leg edema, hepatomegaly, and a paradoxical pulse were noted on physical examination. The erythrocyte sedimentation rate was elevated and the C-reactive protein was 2.8 mg/dl. Antinuclear antibodies and anti-SS-A/Ro antibodies were present. The scl-70 and anticentromere antibodies were elevated. Chest radiography showed cardiomegaly. Echocardiography revealed a large pericardial effusion, but the pericardial fluid did not contain malignant cells or bacteria. She did not meet the diagnostic criteria for any known connective tissue diseases, so was diagnosed with cardiac tamponade due to UCTD. Prednisolone (30 mg/day) was administered, which resulted in a gradual resolution of the pericardial effusion. Although connective tissue diseases are known to cause pericardial effusion, cardiac tamponade as the initial manifestation of the disease in the absence of other symptoms is quite rare.

Aged↗
PubMed2000

Protective effect of TA-993, a novel therapeutic agent for peripheral circulatory insufficiency, on skeletal muscle fatigue in a rat model of hindlimb ischemia.

TA-993 (cis-(-)-2-(4-methylphenyl)-3-acetoxy-2,3-dihydro-5-(2-dimethylaminoethy l)-8-methyl1,5-benzothiazepine-4(5H)-one maleate), a new 1,5-benzothiazepine derivative, has a selective increasing action on limb blood flow in addition to an antiplatelet action. In this report we studied the effect of TA-993 on a time dependent decrease in developed tension of electrically-induced contraction of tibialis anterior muscle in a rat model of peripheral circulatory insufficiency induced by occlusion of abdominal aorta. In our preparation, the developed tension decreased by 20-30% in a sham-operated group and 30-40% in an abdominal aorta-occluded group at the end of the experimental period of 60 min. Intraduodenal administration (i.d.) of TA-993 (10 mg/kg) to the abdominal aorta-occluded rats ameliorated the decrease in developed tension to the level of the sham-operated group. Moreover, TA-993 at 10 mg/kg, i.d. significantly increased femoral arterial blood flow supplied through collateral circulation and decreased the whole blood viscosity in this model. These results suggest that TA-993 improves dysfunction of skeletal muscle contraction due to peripheral circulating insufficiency through an increase in collateral blood flow and an improvement of red blood cell deformability.

Animals↗
PubMed2000

[Papillary adenocarcinoma of the prostate: report of 3 cases].

We report here 3 cases of papillary adenocarcinoma of the prostate. In all 3 cases, the tumors were discernible on cystourethroscopy and transurethral biopsy established the diagnosis, whereas no significant finding was found on digital rectal examination. Although androgen deprivation therapy was administered in all cases, different surgical procedures were employed according to the stage in each case. In case 1, since the papillary tumor was confined within the prostatic urethra, complete resection was accomplished by transurethral resection (TUR). In case 2, since pelvic lymph nodes metastases were found, local radiation therapy was added. In case 3, since the patient had vesical invasion of tumor total cysto-prostatectomy was performed. Papillary adenocarcinoma of the prostate originates from the prostatic duct, resulting in existence at the "central portion" of the prostate gland. Cystourethroscopy and transurethral biopsy is helpful for diagnosis of this disease, whereas rectal digital examination is useless. As a surgical procedure for the primary site, TUR may be efficient for tumors confined within the prostatic urethra, although more extensive surgery may be necessary for those with a more invasive profile.

Adenocarcinoma, Papillary↗
PubMed2000

Angiographic coronary morphology in patients with ischemic heart disease.

OBJECTIVES: To determine whether ischemia- or infarct-related arteries (IRAs) are accompanied by certain findings specific to clinical settings, coronary cineangiography was reviewed of 71 patients with stable effort angina pectoris (SAP), 72 with unstable angina pectoris (UAP), 118 with acute myocardial infarction (AMI) and 137 with old myocardial infarction (OMI). METHODS: The morphology of identifiable ischemia- or infarct-related lesions (IRLs) was classified as totally occlusive, and simple (Type I lesion) or complex (Type II lesion). Complex lesions were subdivided into Type IIa lesions (narrowing with irregular, poorly defined or hazy borders, sharp leading or trailing edges that overhang or are perpendicular to vessel walls, and globular endoluminal negative images), Type IIb (2 or more serial, closely spaced narrowings together with multiple irregularities), Type IIc (luminal narrowing with extraluminal contrast pooling, single or paired short thin linear radiolucencies with or without a variable degree of outpouching, and narrowing with definite outpouching with or without radiolucency), and Type IId (narrowing with morphology not included in Types IIa-IIc). RESULTS: Total occlusive lesions among identifiable IRLs occurred at 17 sites (23.9%) in patients with SAP, 7 (9.7%) with UAP, 48 (40.7%) with AMI and 30 (21.9%) with OMI. The mean diameter stenosis of identifiable IRLs was 89.4% in patients with SAP, 92.0% with UAP, 93.1% with AMI, and 87.4% with OMI. Patent identifiable IRLs in patients with SAP had a significantly higher frequency of Type I lesions (29 sites, 40.8%) compared with those with UAP, AMI and OMI (p < 0.01), followed by a relatively lower occurrence of Types IIa 12 (16.9%), IIb 8 (11.3%), IIc 3 (4.2%) and IId 2 (2.9%) lesions. Patients with UAP were characterized by a higher occurrence of Type IIa (34 sites, 47.2%, p < 0.01) and IIc (13 sites, 18.1%, p < 0.01) lesions compared with those with SAP. Patients with AMI had total occlusion (48 sites, 40.7%, p < 0.05) and Type IIa lesion (38 sites, 32.2%, p < 0.05) more frequently than those with SAP. Patients with OMI showed fewer total occlusions (30 sites, 21.9%), same occurrence of Type IIa lesion (39 sites, 28.5%), and higher occurrence of IIb (23 sites, 16.8%) and IIc (20 sites, 14.6%) than those with AMI. CONCLUSIONS: This analysis of coronary cineangiographies from patients with UAP, AMI and OMI, which share a common pathogenesis, shows that IRAs, especially IRLs, are associated with certain morphology specific to clinical settings, and that the morphology and severity of stenosis could change in a short period. The present results may improve coronary cineangiography interpretation about pathophysiological issues in vivo affecting coronary circulation.

Adult↗
PubMed2000

[Recurrent pulmonary embolism from left subclavian thrombosis: a case report].

A 38-year-old woman was admitted to our hospital because of pulmonary thromboembolism. Thrombolysis therapy resulted in initial improvement in symptoms and laboratory data. However, 4 months later, pulmonary thromboembolism recurred despite antiplatelet and anticoagulation therapy. Contrast venography and venous ultrasonography of both upper and lower extremities revealed subtotal occlusion and venous thrombosis of the left subclavian vein with collateral vessels, but no evidence of lower extremity venous thrombosis. She had no history of subclavian venous catheterization, neoplasm, hypercoagulability or other predisposing cause of thrombus formation. Operative ligation of the left subclavian vein was performed at the junction with the internal jugular vein. White thrombus was identified within the venous lumen. She was well without recurrent pulmonary thromboembolism or venous insufficiency for 10 months after the operation. Surgical interruption of the subclavian vein may be effective to prevent recurrent pulmonary thromboembolism in patients with recurrent pulmonary thromboembolism due to venous thrombosis of the upper extremity despite therapeutic anticoagulation.

Adult↗
PubMed2000

A case-control study of hepatocellular carcinoma in Hyogo Prefecture.

We conducted a case-control study to elucidate factors contributing to the development of hepatocellular carcinoma (HCC) in Hyogo Prefecture, Japan where its incidence is high. In this study, the incidence of hepatitis virus infection in HCC patients and lifestyle factors including dietary and drinking habits were investigated. One hundred and eight patients with HCC (89 males and 19 females) and 93 controls (63 males and 30 females) were enrolled. Hepatitis C virus (HCV) antibody was identified in 87% of cases of which HCV-RNA was further detected in more than 95%. Genotype distribution of HCV was similar to that reported for the Japanese infected with HCV. There was a positive correlation between HCC and history of blood transfusion (both male and female) and surgery (male). Alcohol consumption over a period of 30 years was higher in the HCC patients than in controls; but not significant. These data indicated that HCV infection is a primary contributing factor to the development of HCC in Hyogo Prefecture.

Aged↗
PubMed1999

Pharmacokinetic/pharmacodynamic modeling of antitumor agents encapsulated into liposomes.

Pharmacokinetic/pharmacodynamic (PK/PD) modeling of antitumor agents has been developed for doxorubicin (DOX) in order to predict the optimum conditions for a drug carrier to maximize the antitumor effect. A PK model was constructed for free and liposomal doxorubicin using a hybrid model wherein the disposition in the whole body is described by compartment models, which were linked to the tumor compartment via the blood flow rate. The PD model for doxorubicin was described by a cell-kill kinetic model, which represents the number of tumor cells quantitatively, as a function of the free concentration of doxorubicin in the tumor compartment. The influence of each parameter on the antitumor effects was examined by sensitivity analysis based on the PK/PD model, which clearly showed the importance of optimizing the release rate of DOX from liposomes. The validity of the model has been tested using animal experiments. Preliminary simulations were also performed for humans after scaling up the PK/PD model from rodents to humans. The optimum conditions in the rate of drug release from liposomes were different for rodents vis-a-vis humans, which indicates the limitations involved in extrapolating optimum conditions for experimental animals to those for humans.

Journal Article↗
PubMed1999

Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease.

Background-The circulating levels of secretory nonpancreatic type II phospholipase A(2) (sPLA(2)) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA(2) may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA(2) may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA(2) were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA(2) levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA(2) (>246 ng/dL; 75th percentile of sPLA(2) distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA(2) were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA(2) is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA(2) levels with inflammatory activity in atherosclerotic arteries.

Aged↗
PubMed1999

Remnant lipoprotein levels in fasting serum predict coronary events in patients with coronary artery disease.

BACKGROUND: Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for </=36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (>5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (</=3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. CONCLUSIONS: Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk.

Adult↗
PubMed1999

Stable expression of protective protein/cathepsin A-green fluorescent protein fusion genes in a fibroblastic cell line from a galactosialidosis patient. Model system for revealing the intracellular transport of normal and mutated lysosomal enzymes.

Fibroblastic cell lines derived from a galactosialidosis patient, stably expressing the chimaeric green fluorescent protein variant (EGFP) gene fused to the wild-type and mutant human lysosomal protective protein/cathepsin A (PPCA) cDNA, were first established as a model system for revealing the sorting and processing of lysosomal enzymes and for investigating the molecular bases of their deficiencies. In the cell line expressing the wild-type PPCA-EGFP chimaera gene (EGFP-PPwild), an 81 kDa form (27 kDa EGFP fused to the C-terminus of the 54 kDa PPCA precursor) was produced, then processed into the mature 32/20 kDa two-chain form free of the EGFP domain. The intracellular cathepsin A, alpha-N-acetylneuraminidase and beta-galactosidase activities, which are deficient in the parent fibroblastic cells, could also be significantly restored in the cells. In contrast with the uniform and strong fluorescence throughout the cytoplasm and nucleus in the mock-cell line expressing only EGFP cDNA, weak reticular and punctate fluorescence was distributed throughout the EGFP-PPwild cell line. Bafilomycin A1, a potent inhibitor of vacuolar ATPase and intracellular acidification, induced the distribution of Golgi-like perinuclear fluorescence throughout the living and fixed cells, in which only the 81 kDa product was detected. After removal of the agent, time-dependent transport of the chimaeric protein from the Golgi apparatus to the prelysosomal structure in living cells was monitored with a confocal laser scanning microscope system. Leupeptin caused the distribution of lysosome-like granular fluorescence throughout the cytoplasm in the fixed cells, although it was hardly observed in living cells. The latter agent also dose-dependently induced an increase in the intracellular amount of the 81 kDa product containing the EGFP domain and inhibited the restoration of cathepsin A activity in the EGFP-PPwild cells after the removal of bafilomycin A1. In parallel, both the mature two-chain form and PPCA function disappeared. These results suggested that the chimaera gene product was transported to acidic compartments (endosomes/lysosomes), where proteolytic processing of the PPCA precursor/zymogen, quenching of the fluorescence, and random degradation of the EGFP portion occurred. A cell line stably expressing a chimaeric gene with a mutant PPCA cDNA containing an A1184-->G (Y395C) mutation, commonly detected in Japanese severe early-infantile type of galactosialidosis patients, showed an endoplasmic reticulum (ER)-like reticular fluorescence pattern. The PPCA-immunoreactive gene product was hardly detected in this cell line. The mutant chimaeric product was suggested to be degraded rapidly in the ER before transport to post-ER compartments. A cell line expressing the chimaeric gene with a T746-->A (Y249N) PPCA mutation exhibited both ER-like reticular and granular fluorescence on the reticular structure that was stronger than that in the EGFP-PPwild cells. Some of them contained large fluorescent inclusion-body-like structures. The ineffectiveness of transport inhibitors in the distribution changes in the two mutant chimaeric proteins suggested that they were not delivered to acidic compartments. Therefore this expression system can possibly be applied to the direct analysis of the sorting defects of mutant gene products in living cells and will be useful for the molecular investigation of lysosomal diseases, including galactosialidosis.

Amino Acid Sequence↗
PubMed1999

Suppression of atherosclerotic development in Watanabe heritable hyperlipidemic rabbits treated with an oral antiallergic drug, tranilast.

BACKGROUND: Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: WHHL rabbits (2 months old) were given either 300 mg x kg-1 x d-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast. CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.

Administration, Oral↗
PubMed1999

Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine.

This study examined whether lysophosphatidylcholine (lysoPC), an atherogenic lipid, may stimulate production of O2*-, in cultured human endothelial cells. Production of O2*- was detected by bis-N-methylacridinium nitrate (lucigenin)-elicited chemiluminescence. LysoPC was found to induce burst production of O2*-, peaked at 2-4 min after the stimulation, in intact endothelial cells. LysoPC also stimulated NADH-dependent production of O2*- in particulate fraction of the cells, and the action of lysoPC was inhibited by diphenyliodonium. The results suggested that lysoPC stimulated production of O2*- partly through membrane-associated NADH-dependent O2*- production systems.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1999

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.

OBJECTIVES: This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels. BACKGROUND: Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis. METHODS: Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients). RESULTS: Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.4% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05). CONCLUSIONS: Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction, in patients with high remnants levels.

Adult↗
PubMed1999

Effects of atrial and brain natriuretic peptides on lysophosphatidylcholine-mediated endothelial dysfunction.

Lysophosphatidylcholine (LPC), a major atherogenic lysophospholipid contained in oxidized low-density lipoprotein (ox-LDL), induces endothelial dysfunction. Recent studies showed that natriuretic peptides (NPs) have antiatherogenic properties by inhibiting vascular smooth-muscle cell proliferation, but their effects on endothelial cells are little known. We examined whether atrial and brain NPs (ANP and BNP) have a protecting action against LPC-induced endothelial dysfunction. LPC (10 microM) significantly inhibited thrombin (0.001-1 U/ml)-induced endothelium-dependent relaxation without affecting endothelium-independent relaxation to sodium nitroprusside in isolated porcine coronary arteries. The impaired endothelium-dependent relaxation induced by LPC was prevented by treatment with ANP or BNP (i microM). In cultured bovine aortic endothelial cells (BAECs), LPC (10 microM) significantly attenuated bradykinin (1 microM)-stimulated nitric oxide (NO) release; however, this was prevented by ANP and BNP. Because LPC-induced endothelial dysfunction has been shown to be mediated at least in part by activation of the protein kinase C (PKC)-dependent signaling pathway, we also examined the effects of ANP and BNP on LPC-induced modulation of PKC activities in BAECs. LPC (10 microM) significantly stimulated PKC activity in BAECs. However, ANP or BNP significantly inhibited LPC (10 microM)-induced PKC activation. In conclusion, ANP and BNP protected endothelial cells from LPC-induced dysfunction in both isolated coronary arteries and cultured ECs. The mechanism appears to be at least in part related to the inhibition of LPC-induced PKC activation by NPs. These new actions of ANP and BNP against lysolipid-induced endothelial cytotoxicity may partly account for antiatherogenic properties of NPs.

8-Bromo Cyclic Adenosine Monophosphate↗