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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glomerulosclerosis and atherosclerosis share common pathobiological mechanisms. Experiments carried out in vitro over the past decade using cells thought to be involved in the atherosclerotic process such as endothelial cells, smooth muscle cells, and monocyte/macrophages have shown that postsecretory modifications such as oxidation increase the atherogenicity of LDL. Animal experiments employing antioxidant therapy have also been shown to slow the progression of atherosclerotic lesions. We set out to investigate the interactions between oxidized LDL (oxLDL) and rat mesangial cells (RMC) that might be of importance in the glomerulosclerotic process. Our results show that RMC have the ability to oxidize LDL, that oxLDL binding was 2-3-fold greater than native LDL (nLDL), and that oxLDL was more cytotoxic to these cells than nLDL. We speculate that cell-mediated oxidation of LDL in vivo may play a role in the progression of the glomerulosclerotic process.
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PMID:Oxidation of low-density lipoproteins by rat mesangial cells and the interaction of oxidized low-density lipoproteins with rat mesangial cells in vitro. 839 31

The purpose of this review has been to summarize the effects of lipids on the progression of renal disease in chronic renal failure. Animal studies show that hypercholesterolemia as induced by a high cholesterol diet can aggravate the progression of renal disease in experimental models of chronic renal failure. Hypolipidemic treatment, when given to animals with chronic nephropathy associated with endogenous hyperlipidemia such as in reduced renal mass, obese Zucker rat, PAN nephrosis and the Dahl salt-sensitive rat, results in a reduction in serum lipids levels concomitant with a decrease in the renal damage. Enrichment of the diet with omega-6 PUFA given to rats with reduced kidney mass leads to a reduction in renal damage, probably due to beneficial changes in renal fatty acid composition, while supplementation of a fish oil diet to rats with immune complex nephritis resulted in a similar beneficial effect, probably due to a suppression in the local immunologic processes. The pathogenesis of this effect is still only partially understood. Lipid deposition and oxidation in the renal mesangium, migration of circulatory monocytes into the renal mesangium and their transformation to foam cell, and alterations in renal PUFA metabolism and composition are the main known alterations that accompany lipid-induced renal damage. These alterations, which are similar to those observed in atherosclerosis, lead to alterations in the normal biologic processes in the renal mesangium and terminate in glomerulosclerosis. Extrapolating the data from experimental studies to human renal diseases, it may be assumed that lipid metabolism has a significant impact on the gravity and progression of renal disease in a selected patient population, namely in patients with chronic renal disease. If so, hypolipidemic treatment or administration of certain types of PUFA can be important in the prevention of progression of the renal disease in these patients. Clinical studies are needed to elucidate this issue.
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PMID:Role of lipids in the progression of renal disease in chronic renal failure: evidence from animal studies and pathogenesis. 849 78

Glomerulosclerosis is the final common glomerular lesions in many renal diseases. The histological features of focal glomerulosclerosis resemble the lesion of atherosclerosis and may indicate a parallel pathogenesis. Central to the pathogenesis of atherosclerosis is the interaction of blood cells and endothelial cells with subsequent proliferation of smooth muscle cells and enhanced production of collagen. The mechanisms that appear to be responsible for this increased proliferative response are growth factors, cytokines, and local alterations in the extracellular matrix. The corresponding counterparts in glomerulosclerosis include mesangial expansion with mesangial cell proliferation, mesangial foam cell accumulation, tissue necrosis, and eventual sclerosis. Substances that interfere with the interaction between the different cell types, such as endothelial cells, macrophages, and platelets, and with the proliferative responses of both vascular and mesangial cells may be of therapeutic value in both diseases. Calcium antagonists interfere with the cellular activation induced by growth factors and vasoactive hormones and, in platelets, they decrease aggregation and the secretion of thromboxane from these cells. In addition to their relaxant effect, calcium antagonists diminish the proliferative response of vascular smooth muscle and mesangial cells to growth factors while, in macrophages, production of superoxides is decreased after incubation with calcium antagonists. In mesangial cells it has been demonstrated that calcium antagonists decrease the expression and secretion of matrix proteins. That these cellular mechanisms result in an anti-atherosclerotic effect in vivo has been shown by various animal studies, and a beneficial effect of calcium antagonists on the progression of glomerulosclerosis has also been observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium antagonists and cellular mechanisms of glomerulosclerosis and atherosclerosis. 850 31

Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9-month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation.
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PMID:[Study on the glomerular foam cells in stroke-prone SHR]. 851 96

Disordered lipoprotein metabolism and the enhanced influx and accumulation of circulating mononuclear leukocytes into vascular tissue are common pathobiological phenomena associated with both atherosclerosis and glomerulosclerosis. Since atherogenic lipoproteins (such as low density lipoprotein, LDL) have been implicated in monocyte migration and proliferation into the glomerular mesangium, we examined the effect of LDL on mesangial cell expression of macrophage colony-stimulating factor (M-CSF), a cytoregulatory peptide associated with monocyte chemoattraction, differentiation and proliferation. Mesangial cell M-CSF gene expression, protein synthesis and secretion, and its biological activity to induce progenitor colony formation and monocyte proliferation were studied in murine mesangial cells. Incubation of either primary cultures or SV-40 transformed murine mesangial cells with LDL (0 to 200 micrograms/ml) induced M-CSF steady-state mRNA expression, in a dose-dependent manner (52 to 183% of control) when Northern blots were analyzed quantitatively by densitometric scanning. Similarly, Western blot analysis showed that LDL-activated SV-40 transformed mesangial cells increased M-CSF protein synthesis and secretion in a dose-dependent manner. The conditioned media obtained by incubating mesangial cells with LDL induced bone marrow progenitor colony formation that could be inhibited by specific neutralizing antibodies against murine M-CSF. Finally, the biological activity of M-CSF secreted by LDL-activated mesangial cells was further confirmed by its enhanced ability to induce monocyte proliferation. These data indicate that LDL, by activating mesangial cells to induce M-CSF and possibly other monocyte chemoattractants, may regulate the migration and proliferation of cells of mononuclear leukocytic origin into the mesangium supporting a pathobiological role for LDL in glomerular injury.
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PMID:Low-density lipoprotein stimulates the expression of macrophage colony-stimulating factor in glomerular mesangial cells. 856 87

Chronic renal allograft dysfunction is often associated with hypertension, but it is unknown to what extent this affects graft structure and function. We investigated the effect of antihypertensive drug treatments on the course and histopathology of chronic renal allograft rejection in a rat model. Recipient animals were treated with a combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L158,809. Systemic blood pressures and tubular stop-flow pressures were measured on day 50 after transplantation; the histopathology was assessed semiquantitatively in kidneys not used for micropuncture studies. Grafts removed from untreated recipients showed inflammation and structural vascular and glomerular lesions consistent with chronic rejection. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with improved graft survival, decreased proteinuria and a tendency to improved graft function; the histopathology showed a significant amelioration of glomerular mesangiolysis and glomerulosclerosis but no effect was found on the tubulointerstitial lesions; the angiotensin receptor blocker also inhibited graft atherosclerosis. We conclude that hemodynamic and angiotensin II-mediated processes may play a pivotal role in the expression of immune-mediated glomerular lesions of chronic allograft dysfunction.
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PMID:Post-transplant hypertension and chronic renal allograft failure. 858 80

Chronic ischemia may cause end stage renal disease, especially in older patients with atherosclerotic renal artery stenosis. Examining the pathology of the ischemic kidney is a fundamental first step toward understanding the mechanisms of this injury. In experimental renal hypoperfusion, there is evidence of a mixture of adaptive responses, tubular and endothelial cell damage and repair events. These processes are reflected in a wide spectrum of morphological changes that include atrophy, focal necrosis, epithelial regeneration, apoptosis, inflammation, interstitial fibrosis, and thrombosis. The most severe damage is seen in the outer medulla, a region with marginal oxygenation even in normal circumstances. In the usual clinical case, the effects of aging, pre-existent hypertension, and the process of atherosclerosis further complicate the pathological picture. Lesions related to these factors include arteriosclerosis, athero-emboli, various types of glomerulosclerosis, and severe tubulointerstitial damage leading to "atubular glomeruli" and regional cortical scarring (nephrosclerosis). In this article, some mechanisms determining the varied and complex pathological findings that may be observed in individual cases are outlined.
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PMID:The pathology of chronic renal ischemia. 872 83

The nephrotic syndrome is frequently associated with hyperlipidaemia and hyperfibrinogenaemia, leading to an increased coronary and thrombotic risk, which may be enhanced by high lipoprotein (a) [Lp(a)] concentrations. We followed the quantitative and qualitative pattern of plasma lipoproteins over 18 months in a patient with nephrotic syndrome suffering from premature coronary artery disease and with elevated level of Lp(a) (470 mg dL-1). Analysis of kinetic parameters after heparin-induced extracorporeal plasma apheresis revealed a reduced fractional catabolic rate for both low-density lipoprotein (LDL) and Lp(a). After improvement of the nephrotic syndrome, Lp(a) decreased to 169 mg dL-1 and LDL concentrations were normalized. The decrease of Lp(a) was associated with an increase in plasma albumin concentrations. Analysis of apo(a) isoforms in the patient showed the presence of isoform S2 (alleles 10 and 19). Consequently, the authors' present strategy is to normalize the elevated Lp(a) and fibrinogen levels. For this purpose heparin-mediated extracorporeal LDL precipitation (HELP) apheresis is a promising regimen, helping to reduce the thrombotic risk and prevent coronary and graft atherosclerosis as well as the progression of glomerulosclerosis in our patient.
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PMID:Hyperlipoprotein(a)aemia in nephrotic syndrome. 873 90

Diabetic nephropathy can be regarded mainly as a type of microangiopathy, but is a disease that may also include aspects of macroangiopathy. This is especially true of renal disease in non-insulin dependent diabetes mellitus (NIDDM), which is characterized not only by diabetic glomerulosclerosis, but also by atherosclerosis. We performed morphological studies on the kidney, using computed tomography (CT), focusing on such points as: (1) abdominal aortic calcifications at the level of kidney, (2) calcifications in the renal artery, and (3) wedge-shaped defects on the renal surface. We noted that these findings became more prominent in NIDDM patients during end-stage renal failure than during normal renal function, and were significantly more common in those two NIDDM groups than in age-matched nondiabetic patients without hypertension, hyperlipidemia or gout. NIDDM patients exhibited these features more frequently than IDDM patients.
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PMID:[Computed tomographical evaluation of diabetic nephropathy]. 875 67

Platelets (PLT) play an important role in hemostasis, modulation of immunological and inflammatory processes. There is also evidence that PLT takes part in the development of atherosclerosis and glomerulosclerosis. The aim of presented study was to determine morphological and functional changes of platelets and their relation to the lipid, protein and coagulation factors disturbances in patients with chronic glomerulonephritis (CGN). The studies were carried out in 60 patients with CGN diagnosed by renal biopsy: 30 patients without nephrotic syndrome (NS)-CGN and 30 patients with NS-CGN+NS. Protein and lipid disturbances, coagulation factors were estimated using routine laboratory methods. Platelet count (PLT), mean platelet volume (MPV) and modal platelet volume (PLT-Mode) were measured using Technicon H1 hematological autoanalyser. Platelet function was assessed by aggregometry using turbidimetric method (inductors: ADP 1-3 microM, collagen 50g/ml, epinephrine 0.25-5 microM). Spontaneous platelet aggregation (SPA) was measured in platelet rich plasma (PRP) without inductors for 15 min, in 1-2 hours after venesection. SPA was observed in 9 of 30 patients with CGN and in 19 of 30 patients with CGN+NS. MPV and PLT Mode were significantly higher in patient showing SPA compared with those without. Significant correlations between SPA and the concentration of plasma albumin (r = -0,70; p < 0.02) TG and CH-LDL (r = 0,61; p < 0.05) were found in CGN+NS patients. APTT was significantly shorter in patients showing SPA compared with those without and negative significant correlation between SPA and APTT was found. Platelet aggregation to inductors in CGN and CGN+NS patients was diminished compared with control group. Lack of second phase aggregation in response to aggregation inducers was observed in patients with SPA. Conclusions. 1. Platelet hyperaggregation play an important role in hypercoagulation state in CGN patients. 2. SPA in vitro was observed in majority of CGN+NS patients and in some without NS. 3. Pathomechanism of SPA is probably multifactorial (hypoalbuminemia, dyslipidemia, changes in concentration of coagulation parameters).
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PMID:[Evaluation of factors influencing platelet aggregation in patients with chronic glomerulonephritis (CGN)]. 875 9


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