Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice

Zen, Ayman Al Haj; Caligiuri, Giuseppina; Sainz, Julie; Lemitre, Mathilde; Demerens, Corinne; Lafont, Antoine

doi:10.1016/j.atherosclerosis.2005.08.023

Cited by 44 publications

(36 citation statements)

References 37 publications

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“…51 However, decorin overexpression in mice was associated with decreased atherosclerosis development, 53 and studies examining atherosclerosis in mice heterozygous for perlecan (perlecan deficiency is lethal) are complex, with only male apoE Ϫ/Ϫ mice showing decreased atherosclerosis, and no differences in atherosclerosis extent in female apoE Ϫ/Ϫ or either gender of LDLR Ϫ/Ϫ mice. 54 A recent study using apoE Ϫ/Ϫ mice that express perlecan lacking heparan sulfate glycosaminoglycan chains demonstrated decreased atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

Wilson

Thompson

Webb

et al. 2008

The American Journal of Pathology

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Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are predictive of cardiac disease and are proposed to play causal roles in the development of atherosclerosis, in which the retention of lipoproteins by vascular wall proteoglycans is critical. The purpose of this study was to determine whether SAA and/or CRP alters vascular proteoglycan synthesis and lipoprotein retention in a pro-atherogenic manner. Vascular smooth muscle cells were stimulated with either SAA or CRP (1 to 100 mg/L) and proteoglycans were then isolated and characterized. SAA, but not CRP, increased proteoglycan sulfate incorporation by 50 to 100% in a dose-dependent manner (P < 0.0001), increased glycosaminoglycan chain length, and increased low-density lipoprotein (LDL) binding affinity (K d , 29 g/ml LDL versus 90 g/ml LDL for SAA versus control proteoglycans; P < 0.005). Furthermore, SAA up-regulated biglycan via the induction of endogenous transforming growth factor (TGF)-␤. To determine whether SAA stimulated proteoglycan synthesis in vivo, ApoE ؊/؊ mice were injected with an adenovirus expressing human SAA-1, a null virus, or saline. Mice that received adenovirus expressing SAA had increased TGF-␤ concentrations in plasma and increased aortic biglycan content compared with mice that received either null virus or saline. Thus, SAA alters vascular proteoglycans in a pro-atherogenic manner via the stimulation of TGF-␤ and may play a causal role in the development of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

Wilson

Thompson

Webb

et al. 2008

The American Journal of Pathology

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“…Of significance and great relevance, a recent study in patients with type 1 diabetes found a close link between an adiponectin single nucleotide polymorphisms and diabetic nephropathy, 48 suggesting that alteration of adiponectin may contribute to diabetic nephropathy. The cause of death in the decorin-deficient diabetic mice is presently unclear, although it is intriguing that decorin may play a protective role in cardiovascular disease, 17,19 and adiponectin levels have been linked with cardiovascular disease in patients with type 1 diabetes 43,44 and mortality with chronic renal disease. 30,31 The second unexpected finding was that the decorindeficient mice exhibited increased renal expression of Nox4, the NADPH oxidase isoform that has been closely mice and plated onto 24-well plates.…”

Section: Discussionmentioning

confidence: 99%

“…13 Second, the expression of decorin is increased during the development of diabetic kidney disease, 15,16 suggesting a role in the pathobiology of the disease, possibly as a compensatory response to antagonize local TGF-␤ activity. Third, decorin has been implicated as a protective factor in atherosclerotic vascular disease, [17][18][19] and therefore decorin deficiency may promote a systemic vasculopathy found in diabetic kidney disease. Fourth, most of the available animal models of diabetic nephropathy show limited phenotypes that lack key features of the advanced renal pathology that occurs in humans, 20 and thus models are needed that recapitulate the more advanced features of human diabetic nephropathy.…”

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confidence: 99%

Decorin Deficiency Enhances Progressive Nephropathy in Diabetic Mice

Williams

Qiu

Usui

et al. 2007

The American Journal of Pathology

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Decorin, a proteoglycan that inhibits active transforming growth factor-␤, is increased in diabetic nephropathy; however, its functional significance is unclear. In this study, we used low-dose streptozotocin to induce type 1 diabetes in wild-type (C57BL/6J Dcn ؉/؉ ), Dcn ؊/؊ , and Dcn ؉/؊ mice and studied the mice for up to 1 year of diabetes. Decorin gene dose had no effect on severity of diabetes; however, the Dcn ؊/؊ diabetic mice died significantly earlier than nondiabetic controls (57 versus 7.3% mortality). In contrast to wild-type diabetic mice, which failed to develop significant nephropathy, the Dcn ؊/؊ diabetic mice developed a significant increase in albuminuria and plasma creatinine and a concurrent decrease in circulating adiponectin levels. Interestingly, adiponectin levels at 6 months of diabetes were predictive of mortality in diabetic mice.

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“…Extracellular matrix (ECM) remodeling, effected by a group of significant inflammatory molecules, including matrix metalloproteinases (MMPs), may be a key factor in the development of inflammation in the central nervous system. Proteoglycans are thought to cause matrix remodeling and modulate the activity of growth factors and cytokines (3).…”

Section: Introductionmentioning

confidence: 99%

“…Yamaguchi et al (36) demonstrated that DCN is a natural inhibitor of transforming growth factor-β1 (TGF-β1). Al Haj Zen et al (3) reported that DCN reduces inflammation by downregulating TGF-β and IL-1β expression through adenovirus-mediated overexpression of DCN in the human gingival fibroblasts. These studies indicate that inflammatory cytokines explain the change of DCN expression during stroke.…”

mentioning

confidence: 99%

Decreased plasma decorin levels following acute ischemic stroke: Correlation with MMP-2 and differential expression in TOAST subtypes

Zhao

Yang

et al. 2012

Molecular Medicine Reports

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Abstract. Accumulating evidence suggests that extracellular matrix (ECM) remodeling plays a significant role following acute ischemic stroke (AIS). Decorin (DCN) is a well-recognized molecule present in the ECM; however, the role of DCN in AIS remains unknown. The present study aimed to investigate whether plasma concentrations of DCN are altered in patients following an AIS and whether they are correlated with matrix metalloproteinase-2 (MMP-2) levels and other laboratory and clinical variables. Plasma concentrations of DCN were assessed in 102 patients with AIS (less than 7 days) and 120 control subjects using ELISA assays. The correlation between DCN concentrations and MMP-2 levels, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, stroke severity and risk factors were evaluated. The expression of DCN was significantly decreased in patients with AIS (P<0.001), particularly in the large-artery atherosclerosis (LAAS) group. The levels of DCN were positively correlated with MMP-2 (R= 0.332; P<0.001), thus MMP-2 is an independent predictor of DCN concentration (P<0.001). DCN levels below 8,500 pg/ml had sensitivity and specificity values of AIS of 79.4 and 62.8%, respectively and DCN below 8,500 pg/ml was associated with AIS (OR=4.8; 95% CI: 2.1-11.1; P<0.001) following adjustment for potential confounders. In conclusion, for the first time, a reduction in DCN was detected in patients following AIS and these altered plasma concentrations were correlated with MMP-2. Larger studies are required to further investigate whether DCN is involved in the pathogenesis of ischemic stroke.

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Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice

Cited by 44 publications

References 37 publications

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

Decorin Deficiency Enhances Progressive Nephropathy in Diabetic Mice

Decreased plasma decorin levels following acute ischemic stroke: Correlation with MMP-2 and differential expression in TOAST subtypes

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