Oxidized‐LDL levels are changed during short‐term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria

Paniagua, Juan Antonio Pacheco; López‐Miranda, José; Pérez-Martínez, Pablo; Marín, C.; Vida, José María Gómez; Fuentes, Felipe; Puebla, Rafael Ángel Fernández de la; Pérez‐Jiménez, Francisco

doi:10.1111/j.1464-5491.2005.01703.x

Cited by 21 publications

(14 citation statements)

References 60 publications

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“…Previous studies have investigated the relationship between oxLDL and FMD in specific patient populations (11)(12)(13), but this relation has not yet been evaluated in a large-population-based sample. We have used FMD data from the Hoorn Study, a community-based cohort study among elderly men and women, to assess the suitability of the oxLDL/LDL-c and oxLDL/apoB100 ratios to correct for LDL particle number.…”

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confidence: 99%

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Zwan

Teerlink

Dekker

et al. 2009

Journal of Lipid Research

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Circulating oxidized LDL (oxLDL) levels are strongly correlated to LDL-cholesterol (LDL-c) and apolipoprotein-B100 (apoB100), making it difficult to disentangle their independent contributions to cardiovascular risk. We explored the determinants of oxLDL and the relation between oxLDL and flow-mediated dilation (FMD) of the brachial artery to investigate whether the oxLDL/LDL-c and oxLDL/apoB100 ratios are more informative than the separate variables. FMD of the brachial artery and plasma concentrations of oxLDL, LDL-cholesterol, and apoB100 were measured in 624 men and women (age range 50 to 87 years), participating in a population-based cohort study. OxLDL was strongly correlated with apoB100 (r 5 0.82, P , 0.001) and LDL-c (r 5 0.67, P , 0.001). Other major independent determinants of oxLDL were sex, HDL-cholesterol, and LDL particle size. LDL-c and apoB100 concentrations were not significantly associated with FMD. After adjustment for age, sex, glucose tolerance status, and Framingham risk score, the oxLDL/apoB100 ratio was negatively related to FMD (P 5 0.017). This association was weaker for the oxLDL/ LDL-c ratio (P 5 0.062) and absent for oxLDL level (P 5 0.27). In contrast to oxLDL, the oxLDL/ apoB100 ratio, and to a lesser extent the oxLDL/LDL-c ratio, are related to a functional measure of atherosclerosis. Therefore correction of oxLDL for LDL particle number may improve the clinical usefulness of oxLDL measurement.-van der

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confidence: 99%

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Zwan

Teerlink

Dekker

et al. 2009

Journal of Lipid Research

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“…Although it is widely accepted that oxidative stress serves to impair endothelial function, only a limited numbers of studies have demonstrated the correlation between the plasma markers of oxidative stress, such as TBARS and oxLDL, and the extent of FMD in clinical studies. 31,32 In the preliminary study, we did not find correlations between plasma TBARS or 8-iso PGF2α levels and the plasma BH4/BH2 ratio or FMD (%) (data not shown). Although the source of plasma pteridine has not been clarified yet, it is assumed that plasma levels of pteridine reflect endothelial pteridine metabolism because the endothelium is directly in contact with blood and is the major site for formation of peroxynitrite that oxidizes BH4.…”

Section: Discussionmentioning

confidence: 71%

Plasma Tetrahydrobiopterin/Dihydrobiopterin Ratio A Possible Marker of Endothelial Dysfunction

Takeda

Yamashita

Shinohara

et al. 2009

Circ J

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Circ J 2009; 73: 955 -962 ndothelial dysfunction (ED) plays a critical role in the initiation and progression of atherosclerosis 1,2 and is associated with risk factors for coronary artery diseases, including smoking, hypertension, hyperlipidemia, diabetes mellitus and obesity. [3][4][5][6][7] Furthermore, endothelial function was demonstrated to serve as a predictor of cardiovascular events. 8,9 Therefore, the evaluation of endothelial function is important to determine the therapeutic strategy for atherosclerotic diseases.Clinically, endothelial function has mostly been evaluated by the extent of endothelium-dependent relaxation (EDR), which is almost exclusively mediated by nitric oxide (NO). Particularly, flow-mediated vasodilatation (FMD) induced by reactive hyperemia following the release of a forearmoccluding cuff is an established method for assessing endothelial function. 10 By using this technique, the relationships between coronary risk factors and the ED have been assessed in many clinical studies, and the close linkage has been reported between endothelial function of the brachial artery and that of the coronary arteries. 11 Now it is well recognized that the extent of ED depends on the burden of coronary risk factors. 12 There have been, however, no reliable plasma markers found for ED in humans. When EDR is used as a standard representing endothelial function, only limited numbers of clinical studies have shown a correlation between a given plasma marker and EDR. 13,14 Oxidative stress has been shown as an important factor leading to ED. Oxidative stress oxidizes tetrahydrobiopterin (BH4), an essential cofactor for endothelial type NO synthase (eNOS), to its oxidative form 7, 8-dihydrobiopterin (BH2) in vascular tissue, particularly in the endothelium. 15,16 The resultant relative deficiency of BH4 causes the uncoupling of the L-arginine-NO pathway (uncoupling of eNOS), which is at least partly involved in the ED in various vascular disorders. 16,17 In certain pathological conditions such as renal failure, changes in plasma BH4 and BH2 have been reported. 18 As oxidative stress is the major factor damaging endothelial (Received September 8, 2008; revised manuscript received December 19, 2008; accepted December 25, 2008; released Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results:In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients wi...

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“…Evidence also suggests that dyslipidaemia may promote retinal microvascular inflammation and the formation of pericyte ghosts in diabetes, independently of hyperglycaemia [27,28]. Modification of LDL by glycation and oxidation represents a qualitative dyslipidaemia that is accentuated in both type 1 and type 2 diabetes [9][10][11]. Although a role of modified LDL in the development of macrovascular disease (atherosclerosis) is well documented, its involvement in diabetic retinopathy is less clear.…”

Section: Discussionmentioning

confidence: 99%

“…LDL modified by oxidation and glycation, is elevated in diabetic plasma [9][10][11] and is established as playing an important role in atherogenesis in both diabetic and non-diabetic patients [12]. However, its role in diabetic retinopathy is less clear.…”

Section: Introductionmentioning

confidence: 99%

Oxidised, glycated LDL selectively influences tissue inhibitor of metalloproteinase-3 gene expression and protein production in human retinal capillary pericytes

Barth

Song

et al. 2007

Diabetologia

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Aims/hypothesis Matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitor of metalloproteinases (TIMPs), regulate important biological processes including the homeostasis of the extracellular matrix, proteolysis of cell surface proteins, proteinase zymogen activation, angiogenesis and inflammation. Studies have shown that their balance is altered in retinal microvascular tissues in diabetes. Since LDLs modified by oxidation/ glycation are implicated in the pathogenesis of diabetic vascular complications, we examined the effects of modified LDL on the gene expression and protein production of MMPs and TIMPs in retinal pericytes.Methods Quiescent human retinal pericytes were exposed to native LDL (N-LDL), glycated LDL (G-LDL) and heavily oxidised and glycated LDL (HOG-LDL) for 24 h. We studied the expression of the genes encoding MMPs and TIMPs mRNAs by analysis of microarray data and quantitative PCR, and protein levels by immunoblotting and ELISA. Results Microarray analysis showed that MMP1, MMP2, MMP11, MMP14 and MMP25 and TIMP1, TIMP2, TIMP3 and TIMP4 were expressed in pericytes. Of these, only TIMP3 mRNA showed altered regulation, being expressed at significantly lower levels in response to HOG-vs N-LDL. Quantitative PCR and immunoblotting of cell/matrix proteins confirmed the reduction in TIMP3 mRNA and protein in response to HOG-LDL. In contrast to cellular TIMP3 protein, analysis of secreted TIMP1, TIMP2, MMP1 and collagenase activity indicated no changes in their production in response to modified LDL. Combined treatment with N-and HOG-LDL restored TIMP3 mRNA expression to a level comparable with that after N-LDL alone. Conclusions/interpretation Among the genes encoding for MMPs and TIMPs expressed in retinal pericytes, TIMP3 is uniquely regulated by HOG-LDL. Reduced TIMP3 expression might contribute to microvascular abnormalities in diabetic retinopathy.

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Oxidized‐LDL levels are changed during short‐term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria

Cited by 21 publications

References 60 publications

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Plasma Tetrahydrobiopterin/Dihydrobiopterin Ratio A Possible Marker of Endothelial Dysfunction

Oxidised, glycated LDL selectively influences tissue inhibitor of metalloproteinase-3 gene expression and protein production in human retinal capillary pericytes

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