Proteoglycans can mediate renal lipoprotein retention

Tannock, Lisa R.

doi:10.1007/s00125-006-0181-z

Cited by 6 publications

(9 citation statements)

References 6 publications

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“…We and others have shown that TGF-b potently upregulates vascular proteoglycan synthesis and stimulates the synthesis of longer glycosaminoglycan chains with increased LDL binding affinity (30,35,48). Our findings that angII infusions increased plasma TGF-b levels, and that TGF-b-neutralizing antibodies inhibited the effect of angII to increase proteoglycan synthesis and size in vitro, suggest that angII-induced increased TGF-b is a mechanism by which angII increases LDL retention and atherosclerosis development.…”

Section: Discussionsupporting

confidence: 60%

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Huang

Thompson

Wilson

et al. 2008

Journal of Lipid Research

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Angiotensin II (angII) is known to promote atherosclerosis; however, the mechanisms involved are not fully understood. To determine whether angII stimulates proteoglycan production and LDL retention, LDL receptordeficient mice were infused with angII (1,000 ng/kg/min) or saline via osmotic minipumps. To control for the hypertensive effect of angII, a parallel group received norepinephrine (NE; 5.6 mg/kg/day). Arterial lipid accumulation was evaluated by measuring the retention rate of LDL in isolated carotid arteries perfused ex vivo. Mice infused with angII had increased vascular content of biglycan and perlecan and retained twice as much LDL as saline-or NEinfused mice, although no group developed atherosclerosis at this time. To determine whether this increase in biglycan and perlecan content predisposed to atherosclerosis development, mice were infused with angII, saline, or NE for 4 weeks, then pumps were removed and mice received an atherogenic Western diet for another 6 weeks. Mice that had received angII infusions had 3-fold increased atherosclerosis compared with mice that had received saline or NE, and apolipoprotein B colocalized with both proteoglycans. Thus, one mechanism by which angII promotes atherosclerosis is increased proteoglycan synthesis and increased arterial LDL retention, which precedes and contributes to atherosclerosis

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Section: Discussionsupporting

confidence: 60%

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Huang

Thompson

Wilson

et al. 2008

Journal of Lipid Research

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“…Furthermore, we and others have demonstrated that proteoglycans synthesized by cells stimulated with TGF-␤ have longer glycosaminoglycan chains and increased LDL binding affinity. 20,35,46 Thus, we propose that in diabetes the increased systemic and renal TGF-␤ activity stimulates renal biglycan synthesis with elongated glycosaminoglycan chains. Although all proteoglycans are capable of binding LDL, in our model biglycan is the predominant proteoglycan within the glomerulus.…”

Section: Discussionmentioning

confidence: 94%

“…[17][18][19] Previously, we demonstrated that renal proteoglycans exhibit high-affinity binding to LDL, with affinity constants in the plausible physiological range (K d 14 Ϯ 5 g/mL LDL). 20 Thus, similar to atherosclerosis, renal lipid accumulation could be mediated, at least in part, via retention by renal proteoglycans. However, it is controversial whether proteoglycans accumulate in the mesangium of diabetic nephropathy.…”

mentioning

confidence: 99%

Renal Accumulation of Biglycan and Lipid Retention Accelerates Diabetic Nephropathy

Thompson

Wilson

Brandewie

et al. 2011

The American Journal of Pathology

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Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy.

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“…Mesangial cell proteoglycans exhibit high-affinity binding to LDL with affinity constants in the plausible physiological range (K d = 14 ± 5 µg/mL LDL); proteoglycans synthesized by TGF-β-stimulated mesangial cells have increased LDL binding affinity. 26 These findings suggest that lipoproteins that enter the mesangium can bind to matrix proteoglycans and then be taken up by mesangial cells and/or glomerular macrophages. In further support of this process, we recently demonstrated a striking co-localization of apoB and the proteoglycan biglycan in the glomeruli of diabetic hyperlipidemic mice.…”

Section: Pathophysiology and Effects Of Dyslipidemia In Patients Withmentioning

confidence: 96%

Role of Dyslipidemia in Patients With Chronic Kidney Disease

Marino

Tannock

2013

Postgraduate Medicine

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The presence of dyslipidemia is associated with chronic kidney disease (CKD) in patients and likely contributes to the development of both renal disease and cardiovascular disease (CVD). In vitro and animal studies have demonstrated that renal lipid accumulation is nephrotoxic and can play a role in the initiation and/or progression of renal disease. Data from clinical studies have suggested that dyslipidemia is not causative of renal disease but likely contributes to the progression and severity of renal injury in patients. Cardiovascular disease is the leading cause of morbidity and mortality in patients with CKD, and there is extensive literature that supports the use of lipid-lowering agents to inhibit progression of CVD in patients with CKD. Thus, there is great potential for use of lipid-lowering agents to prevent or inhibit progression of CVD in patients with CKD, and, possibly, to limit progression of CKD for these patients as well. Our article reviews the literature identifying the role of dyslipidemia in the development and progression of renal disease in patients, and the effects of lipid-lowering therapy on the progression of renal disease and development and progression of CVD in patients with CKD. of CKD and reviews the effects of lipid-lowering agents on the progression of CKD, as well as cardiovascular outcomes in patients with CKD.

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Proteoglycans can mediate renal lipoprotein retention

Cited by 6 publications

References 6 publications

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Renal Accumulation of Biglycan and Lipid Retention Accelerates Diabetic Nephropathy

Role of Dyslipidemia in Patients With Chronic Kidney Disease

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