Human β-migrating very low density lipoprotein induces foam cell formation in human mesangial cells

Anami, Yoshichika; Kobori, Shozo; Sakai, Masakazu; Kasho, Masaya; Nishikawa, Takeshi; Yano, Toshihiro; Makino, Hírofumi; Matsumura, Takeshi; Takemura, Tamiko; Shichiri, Motoaki

doi:10.1016/s0021-9150(97)00166-4

Cited by 16 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This may reflect antioxidant and antiinflammatory effects [31]. Triacylglycerols have been linked to nephropathy through mesangial cell uptake of very low-density lipoprotein (VLDL), inducing foam cell formation [32] and through VLDL induction of plasminogen activating inhibitor-1 (PAI-1) with upregulated coagulation and intra-renal microthrombi [33]. HDL does not greatly alter PAI-1 release [34], but has been shown in animals and humans to be reno-protective [35], perhaps through suppression of inflammatory cell adhesion molecules, anti-oxidant effects and reverse cholesterol transport [36,37].…”

Section: Discussionmentioning

confidence: 99%

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

et al. 2010

View full text Add to dashboard Cite

Aims/hypothesis Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Methods Type 2 diabetic patients (n=9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n=4,895) or placebo (n=4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n=661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p<0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p=0.01), with less estimated GFR loss (1.19 vs 2.03 ml min −1 1.73 m −2 annually, p<0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min −1 1.73 m −2 , p=0.065) than on placebo (6.9 ml min −1 1.73 m −2 , p<0.001), sparing 5.0 ml min

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Mesangial cells are specialized glomerular pericytes that share many properties with macrophages [14]. Mesangial cells metabolize lipids similar to macrophages, and they take on the appearance of foam cells after accumulation of lipids [15]. Acute renal tubular injury can also cause down regulation of ABCA1 and SR-BI [16].…”

Section: Introductionmentioning

confidence: 99%

Cellular Cholesterol Transport Proteins in Diabetic Nephropathy

et al. 2014

View full text Add to dashboard Cite

BackgroundLipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy.MethodsProtein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions. Renal expression of these cholesterol transporters was examined in a murine model of streptozotocin-induced type 1 diabetes.ResultsABCA1, ABCG1 and SR-BI were expressed in both human renal mesangial cells and proximal tubular epithelial cells, and mediated cholesterol efflux to apolipoprotein AI and HDL. In vitro, hyperglycemia reduced the expression and the ability to mediate cholesterol efflux of all three cholesterol transporters (p<0.05). In vivo studies showed that intra-renal accumulation of lipids was increased in diabetic mice, particularly in mice with nephropathy. This was associated with a significant reduction in the expression of ABCA1, ABCG1 and SR-BI in the kidneys. These changes were already seen in diabetic mice without nephropathy and preceded the development of nephropathy. Diabetic mice with nephropathy had the lowest level of these cholesterol transporters.ConclusionInducing diabetes with streptozotocin significantly reduced renal expression of ABCA1, ABCG1 and SR-BI. Defects in cholesterol export pathway in renal cells could therefore promote cholesterol accumulation and might contribute to the development of diabetic nephropathy.

show abstract

“…The findings are in conformity with the reports of many researches. Anami et al [5] showed that human β-migrating VLDL induced foam cell formation in human mesangial cells. Palmer et al [22] showed the differential uptake of subfractions of TG-rich lipoproteins by THP-1 macrophage and a preferential accumulation of TG in response to VLDL-1.…”

Section: Discussionmentioning

confidence: 99%

“…Suzaki et al [4] reported, using immunohistochemistry with anti-apoB and anti-apoE antibodies, that apoB and apoE were detected in foam cells in the mesangial region in a patient with familial type III hyperlipoproteinemia associated with diabetes mellitus and nephritic syndrome. In the in vitro study, very-low-density lipoprotein (VLDL)-induced foam cell formation in human mesangial cells was also observed [5]. However, the mechanisms by which VLDL induces lipid accumulation in mesangial cells remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Very-Low-Density Lipoprotein-Induced Triglyceride Accumulation in Human Mesangial Cells Is Mainly Mediated by Lipoprotein Lipase

Li¹,

Li²,

Wen³

et al. 2008

Nephron Physiol

View full text Add to dashboard Cite

Background: Very-low-density lipoprotein (VLDL) in vitro can induce foam cell formation in human mesangial cells. Lipoprotein lipase (LPL) expressed in the arterial wall plays a key role in atherogenesis by actions of enzymolysis and ‘molecular bridge’, and, thereby, leads to the formation of lipid-loaded foam cells. It is known that LPL is expressed by glomerular mesangial cells. This study was designed to investigate if LPL plays a role in VLDL-induced lipid accumulation in human mesangial cells and its underlying mechanism. Methods: Human wild-type LPL (hLPLwt), catalytically inactive LPL (hLPL194) or control alkaline phosphatase (hAP) were expressed in human mesangial cell line (HMCLs) via adenoviral vectors. Orlistat (tetrahydrolipstatin), a specific inhibitor of the lipoidolytic activity of endogenous LPL, and heparinase, which degrades cell-surface heparan sulfate proteoglycans, were also used to estimate the role of either the enzymolysis or ‘molecular bridge’ actions of LPL in the uptake of VLDL. Anti-low-density lipoprotein receptor (LDLr) antibody and anti-LDL receptor-related protein antibody were used to evaluate the effect of lipoprotein receptors on VLDL-induced lipid accumulation in HMCLs. Cellular lipid deposition was visualized by Oil Red O staining and analyzed quantitatively by standard enzymatic procedures. LPL protein expression and activity were measured by Western blot and a chemical analysis, respectively. Results: VLDL induced triglyceride accumulation in HMCLs in a time- and dose-dependent manner. Compared with Ad-hAP transfected HMCLs, cellular triglyceride content increased 4.55-fold (p < 0.05) in Ad-hLPLwt-transfected HMCLs and 1.52-fold (p < 0.05) in Ad-hLPL194-transfected HMCLs. Triglyceride accumulation in response to VLDL was mostly blocked by orlistat. Pretreatment of the cells with heparinase slightly reduced cellular triglyceride accumulation in the present of high concentrations of VLDL. The blockade of some lipoprotein receptors, such as LDLr, did not significantly reduce cellular triglyceride accumulation. LPL expression was upregulated by VLDL. Conclusions: VLDL-induced triglyceride accumulation in human mesangial cells is mainly mediated by LPL, and the enzymolysis action of LPL could be a major factor in this process. These results suggest that LPL may be an important factor participating in the initiation and progression of VLDL-mediated lipid renal injury.

show abstract

Human β-migrating very low density lipoprotein induces foam cell formation in human mesangial cells

Cited by 16 publications

References 30 publications

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

Cellular Cholesterol Transport Proteins in Diabetic Nephropathy

Very-Low-Density Lipoprotein-Induced Triglyceride Accumulation in Human Mesangial Cells Is Mainly Mediated by Lipoprotein Lipase

Contact Info

Product

Resources

About