transforming-growth-factor-beta and Hyperlipidemias

It has been suggested that lipids promote renal injury and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors confer renoprotection in certain renal diseases, including diabetic nephropathy.. Sprague-Dawley rats were randomized to sham, subtotal nephrectomy (STNx) or STNx + atorvastatin groups. After 12 weeks, proteinuria, renal function, glomerular injury, renal transforming growth factor-beta (TGF-beta) gene expression and macrophage (ED1-positive cells) accumulation were assessed. In addition, the effects of HMG CoA reductase in human diabetic nephropathy were reviewed.. Atorvastatin therapy was associated with a modest reduction in proteinuria and glomerulosclerosis without influencing lipid levels or renal function in STNx rats. These effects were associated with decreased renal TGF-beta 1 gene expression and less glomerular and tubulointerstitial macrophage accumulation. The renoprotective effects of HMG CoA reductase inhibitors in both insulin- and non-insulin-dependent diabetic subjects with either incipient or overt nephropathy appear to be highly variable.. HMG CoA reductase inhibition appears to confer renoprotection via effects on prosclerotic cytokines such as TGF-beta and macrophage accumulation, independent of their lipid-lowering properties. The role of lipid-lowering agents in early or overt diabetic nephropathy remains to be fully ascertained.

Topics: Animals; Anticholesteremic Agents; Atorvastatin; Clinical Trials as Topic; Diabetic Nephropathies; Disease Progression; Gene Expression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; In Situ Hybridization; Kidney Diseases; Kidney Glomerulus; Lovastatin; Male; Nephrectomy; Pravastatin; Pyrroles; Rats; Rats, Sprague-Dawley; Simvastatin; Transforming Growth Factor beta

Lipoprotein(a) constitutes a macromolecular complex in human plasma that combines structural features from the blood clotting and the lipoprotein systems. Aside from the discovery of lipoprotein(a) [Lp(a)] as a potential independent risk factor for premature cardiovascular disease its physiological role and activity remains obscure. Since the site of catabolism has not yet been fully characterized, there is intensive search for factors which influence plasma Lp(a) levels. Several clinical conditions and metabolic states have been identified to be added to the disorders of the lipid metabolism itself that modulate Lp(a) plasma levels. Diseases of the kidney and their accompanying factors (proteinuria and nephrotic syndrome) as well as end-stage renal disease and their treatment modalities (hemodialysis, peritoneal dialysis, and kidney transplantation) have all been found to increase Lp(a) plasma levels substantially. Fluctuations in Lp(a) also seem to occur in states of hormonal changes, such as in diabetes mellitus, after estrogen treatment, and during pregnancy. Recently a plausible mechanism for the atherogenic activity of Lp(a) has been ascribed to the inhibiting effect of Lp(a) on plasminogen activation, thus decreasing plasmin formation which in turn reduces the activation of transforming growth factor beta, a potent inhibitor of smooth muscle cell proliferation. Lp(a) exerts its pathological effect at plasma levels in the range of 20-30 mg/dl. Therefore, it seems mandatory to quantitate Lp(a) levels in patients who are at risk of developing progressive atherosclerotic disease to identify those with high levels of this unique atherogenic lipoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arteriosclerosis; Cell Division; Chromosomes, Human, Pair 6; Diabetes Mellitus; Disease Susceptibility; Estrogens; Female; Humans; Hyperlipidemias; Kidney Diseases; Kringles; Lipoprotein(a); Male; Muscle, Smooth, Vascular; Phenotype; Plasminogen; Pregnancy; Risk; Transforming Growth Factor beta

Nephrotic syndrome is defined by proteinuria, hypoalbuminemia, edema and hypercholesterolemia. Evidence from both the experimental and clinical literature suggests that high lipid levels are not only a marker of disease, but also contribute to the process of glomerulosclerosis. Lipid mediators, including eicosanoids, platelet-activating factor, and chemotactic factors, can contribute by effecting leukocyte infiltration, mesangial proliferation, extracellular matrix protein production, vasoreactivity, and coagulation. Infiltrating macrophages may play a central role in these processes. Therapeutic maneuvers aimed at the correction of lipid abnormalities may halt or slow the progression of nephrotic syndrome to end-stage renal disease.

Topics: Animals; Eicosanoids; Glomerulosclerosis, Focal Segmental; Humans; Hyperlipidemias; Macrophages; Nephrotic Syndrome; Platelet Activating Factor; Transforming Growth Factor beta

Hyperlipidaemia causes kidney damage over the long term. We investigated the effect of the administration of endothelial progenitor cells (EPCs) on the progression of kidney damage in a mouse model of hyperlipidaemia.. Our findings demonstrate that hyperlipidaemia causes basement membrane thickening, glomerulosclerosis and the vascular degeneration of endothelial cells. The long-term administration of EPCs substantially has limited effect in the progression of kidney damage in a mouse model of hyperlipidaemia.

Topics: Animals; Apolipoproteins E; Blotting, Western; Bone Marrow Cells; Endothelial Progenitor Cells; Hyperlipidemias; Immunohistochemistry; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction; Smad2 Protein; Smad3 Protein; Splenectomy; Transforming Growth Factor beta

Autoimmune responses to heat-shock protein 60 (HSP60) contribute to the progression of atherosclerosis, whereas immunization with HSP60 may induce atheroprotective responses. We assessed the capacity of an atheroprotective vaccine that targeted a recombinant HSP60 from Porphyromonas gingivalis (rGroEL) to induce a protective mucosal immune response. Female apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice received sublingual delivery of rGroEL prior to P. gingivalis 381 injection. The animals were euthanized 16 weeks later. Sublingual immunization with rGroEL induced significant rGroEL-specific serum IgG responses. Antigen-specific cells isolated from spleen produced significantly high levels of IL-10 and IFN-γ after antigen re-stimulation in vitro. Flow cytometric analysis indicated that the frequencies of both IL-10(+) and IFN-γ(+) CD4(+) Foxp3(+) cells increased significantly in submandibular glands (SMG). Furthermore, sublingual immunization with rGroEL significantly reduced atherosclerosis lesion formation in the aortic sinus and decreased serum CRP, MCP-1, and ox-LDL levels. These findings suggest that sublingual immunization with rGroEL is associated with the increase of IFNγ(+) or IL-10(+) Foxp3(+) cells in SMG and a systemic humoral response, which could be an effective strategy for the prevention of naturally occurring or P. gingivalis-accelerated atherosclerosis.

Topics: Administration, Sublingual; Animals; Antibodies, Bacterial; Apolipoproteins E; Atherosclerosis; Autoantigens; Bacterial Vaccines; C-Reactive Protein; CD4-Positive T-Lymphocytes; Chaperonin 60; Chemokine CCL2; Female; Forkhead Transcription Factors; Hyperlipidemias; Immunity, Mucosal; Immunization; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-4; Lipoproteins, LDL; Mice; Mice, Knockout; Oxidation-Reduction; Porphyromonas gingivalis; Random Allocation; Sinus of Valsalva; Submandibular Gland; Transforming Growth Factor beta

To observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice.. Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia grou. High fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

Topics: Animals; Aorta; Apolipoproteins E; CD36 Antigens; Chemokine CCL2; Dietary Fats; Drugs, Chinese Herbal; Female; Hyperlipidemias; Inflammation; Interleukin-10; Interleukin-12; Interleukin-1beta; Leukocytes, Mononuclear; Mice; Mice, Inbred C57BL; Mice, Knockout; Systemic Inflammatory Response Syndrome; Toll-Like Receptor 4; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Biglycan (BGN), a small leucine-rich proteoglycan, binds the pro-fibrotic cytokine transforming growth factor β (TGFβ) and inhibits its bioactivity in vitro. Nevertheless, it is controversial whether BGN plays an inhibitory role in vivo. Therefore, the purpose of this study was to evaluate the effect of BGN deficiency on TGFβ activity in vivo by studying 1-year-old Bgn null and wild-type (WT) mice on an Ldlr-null background. Phenotypic and metabolic characterization showed that the Bgn null mice had lower body weight, shorter body length, and shorter femur length (all p < 0.05). Surprisingly, the Bgn null mice also exhibited a striking reduction in percent body fat compared to WT mice (p == 0.006), but no changes were observed in plasma triglycerides, total cholesterol, or glycohemoglobin. Both total and bioactive TGFβ1 concentrations in plasma were markedly elevated in Bgn null mice compared to WT mice (4-fold and 11-fold increase, respectively, both p < 0.001), but no changes were found in hepatic levels of mRNA for Tgfβ1 or its receptors. Bgn null mice exhibited elevated expression of hepatic fibronectin protein (p = 0.034) without changes in hepatic or renal histology, and Bgn null mice had decreased urinary albumin/creatinine ratio (p = 0.01). Two key downstream targets of bone morphogenetic protein 4-like signaling, SMAD1/3/5 phosphorylation and Id2 gene expression, were found dramatically reduced in Bgn null livers (p = 0.034). Thus, BGN deficiency decreases body fat in this hyperlipidemic mouse model without changing liver or kidney histology. Overall, we propose that this unexpected phenotype arises from the effects of BGN deficiency in vivo to elevate TGFβ levels while decreasing bone morphogenetic protein 4-like signaling.

Topics: Adipose Tissue; Adiposity; Animals; Biglycan; Body Composition; Body Weight; Bone Morphogenetic Protein 4; Female; Gene Expression Regulation; Hyperlipidemias; Inhibitor of Differentiation Protein 2; Kidney; Kidney Function Tests; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Size; Phosphorylation; RNA, Messenger; Signal Transduction; Smad Proteins; Transforming Growth Factor beta

Cardiac fibrosis is a consequence of many cardiovascular diseases and contributes to impaired ventricular function. Activation of the prostacyclin receptor (IP) protects against cardiac fibrosis, but the molecular mechanisms are not totally understood. Using mouse cardiac fibroblasts, we found that IP activation with cicaprost suppressed expression of collagen I and other target genes of transforming growth factor-beta. This effect of cicaprost was unlikely to be mediated by inhibition of the Smad2/3 or mitogen-activated protein kinase (MAPK) activities, but was associated with cAMP elevation and phosphorylation of the transcription factor cAMP response element binding protein (CREB). Expression of a non-phosphorylated CREB mutant suppressed the inhibitory effect of cicaprost. It appears that phosphorylated CREB binds to and sequestrates the transcription coactivator CBP/p300 from binding to Smad. Inhibition of the intrinsic histone acetyl-transferase activity of CBP/p300 with garcinol significantly suppressed collagen I expression in fibroblasts. Using apolipoprotein E and IP double knockout mouse, we demonstrated that endogenous prostacyclin/IP signaling had an inhibitory effect on angiotensin II-induced cardiac fibrosis under hypercholesterolemic conditions. Taken together, our results suggest that the prostacyclin/IP pathway suppresses cardiac fibrosis, at least partly, by inducing CREB phosphorylation.

Topics: Angiotensin II; Animals; Cell Separation; Collagen; Cyclic AMP Response Element-Binding Protein; Down-Regulation; E1A-Associated p300 Protein; Epoprostenol; Fibroblasts; Fibrosis; Hyperlipidemias; Mice; Mice, Knockout; Models, Biological; Myocardium; NADPH Oxidases; Phosphorylation; Receptors, Epoprostenol; Signal Transduction; Transforming Growth Factor beta

Diabetic kidney disease has been associated with the presence of lipid deposits, but the mechanisms for the lipid accumulation have not been fully determined. In the present study, we found that db/db mice on the FVB genetic background with loss-of-function mutation of the leptin receptor (FVB-Lepr(db) mice or FVBdb/db) develop severe diabetic nephropathy, including glomerulosclerosis, tubulointerstitial fibrosis, increased expression of type IV collagen and fibronectin, and proteinuria, which is associated with increased renal mRNA abundance of transforming growth factor-beta, plasminogen activator inhibitor-1, and vascular endothelial growth factor. Electron microscopy demonstrates increases in glomerular basement membrane thickness and foot process (podocyte) length. We found that there is a marked increase in neutral lipid deposits in glomeruli and tubules by oil red O staining and biochemical analysis for cholesterol and triglycerides. We also detected a significant increase in the renal expression of adipocyte differentiation-related protein (adipophilin), a marker of cytoplasmic lipid droplets. We examined the expression of sterol regulatory element-binding protein (SREBP)-1 and -2, transcriptional factors that play an important role in the regulation of fatty acid, triglyceride, and cholesterol synthesis. We found significant increases in SREBP-1 and -2 protein levels in nuclear extracts from the kidneys of FVBdb/db mice, with increases in the mRNA abundance of acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoA reductase, which mediates the increase in renal triglyceride and cholesterol content. Our results indicate that in FVBdb/db mice, renal triglyceride and cholesterol accumulation is mediated by increased activity of SREBP-1 and -2. Based on our previous results with transgenic mice overexpressing SREBP-1 in the kidney, we propose that increased expression of SREBPs plays an important role in causing renal lipid accumulation, glomerulosclerosis, tubulointerstitial fibrosis, and proteinuria in mice with type 2 diabetes.

Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Nucleus; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; DNA-Binding Proteins; Female; Gene Expression Regulation; Hyperlipidemias; Kidney; Lipid Metabolism; Mice; Mutation; Obesity; Plasminogen Activator Inhibitor 1; Proteinuria; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; Transcription Factors; Transforming Growth Factor beta; Triglycerides; Vascular Endothelial Growth Factor A

Reduction of renal mass is frequently associated with progressive loss of kidney function. We examined the effects of hyperlipidemia on renal pathology and mediators of tissue damage in B6.ROP Os/+ mice, a model of reduced renal mass.. C57BL/6 control mice and B6.ROP Os/+ mice were fed normal rodent chow or a high fat, high cholesterol (HFHC) diet for 12 weeks. Kidney function and renal pathology were assessed.. Hyperlipidemia led to a decline in kidney function in C57BL/6 mice. Renal pathology was characterized by an increase in glomerular matrix and cellularity, glomerular and tubulointerstitial macrophage influx, and increased tubular epithelial cell turnover. Chow-fed B6.ROP Os/+ animals demonstrated glomerular hypertrophy with an increase in mesangial matrix and cellularity that was characterized by macrophage influx and increased proliferation. The tubulointerstitium showed increased macrophages as well as tubular atrophy and dilation. Renal pathology was accompanied by an increase in blood urea nitrogen (BUN) and proteinuria. Hyperlipidemia in B6.ROP Os/+ mice resulted in increased plasma BUN compared to chow-fed B6.ROP Os/+ animals and aggravated renal pathology by further increasing glomerular matrix and glomerular hypercellularity. Glomerular hypercellularity was associated with increased expression of platelet-derived growth factor-B (PDGF B) and its receptor beta. Glomerular transforming growth factor-beta (TGF-beta) mRNA expression was increased in B6.ROP Os/+ mice, hyperlipidemic C57BL/6 mice and hyperlipidemic B6.ROP Os/+ animals compared to controls and correlated with the amount of mesangial matrix.. This study demonstrates that hyperlipidemia worsens renal pathology in B6.ROP Os/+ mice with a decline in renal function mediated at least in part through increased renal expression of the cytokines PDGF B and TGF-beta.

Topics: Animals; Chemokine CCL2; Extracellular Matrix; Female; Glomerular Mesangium; Hyperglycemia; Hyperlipidemias; Hypertrophy; Insulin Resistance; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microscopy, Electron; Obesity; Proto-Oncogene Proteins c-sis; RNA, Messenger; Transforming Growth Factor beta

To evaluate the plasma TGF-beta1 level in erectile dysfunction (ED) patients of various causes.. Sixty-two patients with ED and 26 potent men were subjected to the study. Based on multidisciplinary work-ups, including medical history, physical examinations, blood tests with lipid profile and hormones, penile duplex Doppler ultrasonogram and neurophysiological tests, causes for ED were classified as psychogenic (n=15), neurogenic (n=16) and vasculogenic (n=31). The plasma TGF-beta1 level was measured by the ELISA method.. The plasma TGF-beta1 level was significantly increased in the ED group (6.7+/-4.9 ng/mL), compared to the control (4.0 +/-2.1 ng/mL) (P<0.01). In the ED groups, there was a significant increase in the vasculogenic group (9.0 +/-5.5 ng/mL), compared to the psychogenic (3.8 +/-1.8 ng/mL) and neurogenic groups (4.8+/-3.2 ng/mL) (P<0.01). Of the vascular risk factors, both the smoking (7.5 +/-4.7 ng/mL) and dyslipidemia groups (7.4+/-4.4 ng/mL) showed significantly increased plasma TGF-beta1 levels, compared to the non-smokers (5.5+/-2.8 ng/mL), and those without dyslipidemia (4.8+/-2.8 ng/mL) (P<0.05).. Vascular risk factors are associated with an elevated plasma TGF-beta1 level, which may contribute to cavernous fibrosis and ED.

Topics: Adult; Aged; Arteriosclerosis; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Erectile Dysfunction; Female; Humans; Hyperlipidemias; Hypertension; Impotence, Vasculogenic; Male; Middle Aged; Penis; Risk Factors; Smoking; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ultrasonography

The aim of this article was to examine the protective effect of Chinese traditional medicine angelica on human umbilical vein endothelial cells (HUVECs, ECV304) from injury induced by hyperlipidemic serum (HLS) and to study the underlying mechanism. Spectrophotometer and immunocytochemical methods were used to detect the content of nitric oxide (NO) in suspension and expression of intercellular adhesion molecule-1 (ICAM-1), transforming growth factor beta1 (TGFbeta1), basic fibroblast growth factor (bFGF) on the cell surface, respectively. After incubated with 50 microl/ml HLS for 24 hours, expression of ICAM-1 and bFGF in ECs was significantly increased, while expression of TGFbeta1 and the release of NO from ECs were significantly decreased. All these effect of HLS on ECs can be reversed by angelica significantly. The above effect of angelica may be related to its anti-atherosclerotic action. Our findings provided experimental basement for the clinical application of angelica to prevent the development of atherosclerosis.

Topics: Angelica; Animals; Antioxidants; Cell Culture Techniques; Cell Line; Cytokines; Endothelium, Vascular; Fibroblast Growth Factor 2; Humans; Hyperlipidemias; Intercellular Adhesion Molecule-1; Male; Nitric Oxide; Phytotherapy; Plant Extracts; Rabbits; Transforming Growth Factor beta; Transforming Growth Factor beta1

We examined the role of inflammation in the development of renal interstitial fibrosis in Zucker obese rats, which rapidly present kidney lesions in the absence of hypertension and hyperglycemia. Type I and III collagens were quantified using a polarized light and computer-assisted image analyzer. The expression of mRNA encoding matrix components, adhesion molecules, chemokines, and growth factors was followed by RT-PCR. The presence of synthesized proteins as well as lymphocytes and macrophages was determined by immunohistochemistry. Interstitial fibrosis developed in two phases. The first phase occurred as early as 3 mo and resulted from a neosynthesis of type III collagen and fibronectin and a reduction of extracellular matrix catabolism, in parallel with an overexpression of transforming growth factor-beta(1) and in the absence of any lymphocyte or macrophage infiltration. After 6 mo, interstitial fibrosis worsened with a large accumulation of type I collagen, concomitantly with a large macrophage infiltration. Thus inflammation cannot explain the onset of interstitial fibrosis that developed in young, insulinoresistant, normoglycemic, obese Zucker rats but aggravated this process afterward.

Topics: Animals; Blood Glucose; Collagen; Creatinine; Fibronectins; Fibrosis; Gene Expression; Glomerulosclerosis, Focal Segmental; Hyperinsulinism; Hyperlipidemias; Image Processing, Computer-Assisted; Immunohistochemistry; Lymphocytes; Macrophages; Male; Obesity; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Transforming Growth Factor beta1

Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats. In rats without glomerulonephritis, hyperlipidemia led to a rise in glomerular and ti generation of reactive oxygen species (ROS). Oxygen radicals were mainly generated by enhanced xanthine oxidoreductase (XO), which rose with protein concentration and activity during hyperlipidemia; concurrently, glomerulosclerosis and chronic ti injury were noticed during hyperlipidemia [ti damage (% of total tubulointerstitium (TI) after 150 days): normolipidemia 0.1 +/- 0% vs. hyperlipidemia 3.4 +/- 0. 9%; P < 0.05]. In mesangioproliferative Thy-1 nephritis, ti injury was significantly accelerated by hyperlipidemia (ti damage after 150 days: normolipidemic Thy-1 nephritis 2.5 +/- 0.6% vs. hyperlipidemic Thy-1 nephritis 12.5 +/- 3.1%; P < 0.05). Antioxidant enzyme activities decreased and XO activity rose markedly in the TI (XO activity in TI after 150 days: normolipidemic Thy-1 nephritis 2.2 +/- 0.5 vs. hyperlipidemic Thy-1 nephritis 4.5 +/- 0.7 cpm/microg protein; P < 0.05). In hyperlipidemic Thy-1 nephritis rats, which had a higher urinary protein excretion than normolipidemic rats, hypochlorite-modified proteins, an indirect measure for enhanced myeloperoxidase activity, were detected in renal tissue and in urine, respectively. During hyperlipidemia, chronic damage increased in renal TI. Enhanced generation of ROS, rise in oxidant enzyme activity, and generation of hypochlorite-modified proteins in renal tissue and urine were noticed. These data suggest that oxidant stress contributed to the deleterious effects of hyperlipidemia on the renal TI.

Topics: Animals; Cholesterol, Dietary; Desmin; Dietary Fats; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Hyperlipidemias; Kidney Cortex; Kidney Glomerulus; Luminescent Measurements; Male; Multienzyme Complexes; NADH, NADPH Oxidoreductases; NADPH Oxidases; Nephrectomy; Nephritis, Interstitial; Oxidative Stress; Proteinuria; Rats; Rats, Wistar; Reactive Oxygen Species; RNA, Messenger; Superoxide Dismutase; Transforming Growth Factor beta

to compare patients with abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) with regard to risk factors for atherosclerosis, co-morbid conditions and inflammatory activity.. a total of 155 patients undergoing abdominal aortic surgery between January 1993 and October 1997: 82 (53%) had aneurysmal disease and 73 (47%) had occlusive disease. Principal risk factors were compared: age; gender; smoking; hypertension; hyperlipidaemia; diabetes mellitus; severe peripheral vascular disease (PVD) and ischaemic heart disease. Aortic wall tissue samples were obtained during surgery. A prospective blind analysis was performed for the presence of inflammatory cytokines TNF-alpha, IL-1 beta, IL-6 and TGF-beta.. the average age of AAA patients was 74 years (50-88), while that of AOD patients was 61 years (43-82) (p<0.0001). Diabetes mellitus was found to be much more prevalent in the AOD group (p<0.001), while hypertension and severe PVD were more prevalent in the AAA group (p<0.001). No differences were found concerning any of the risk factors. Inflammatory cytokine activity: AAA tissue samples contained significantly higher mean TNF-alpha and IL-6 levels compared to the AOD samples (5.6+/-2.7 x 10 E-4 vs. 4.4+/-2.7 x 10 E-5 atmoles/microl (p=0. 01), and 0.6+/-0.4 vs. 0.01+/-0.006 atmoles/microl (p=0.02) respectively). No differences were found related to IL-1 beta and TGF-beta.. (1) Patients with AAA have fewer atherosclerotic risk factors than do patients with AOD. (2) Patients with AAA and AOD have significantly different inflammatory activity. (3) The data supports the hypothesis that AAA and AOD are probably two different pathological entities.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Diseases; Coronary Disease; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Interleukin-1; Interleukin-6; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sex Factors; Smoking; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Diseases