Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages

Llaverı́as, Gemma; Noé, Verónique; Peñuelas, Silvia; Vázquez‐Carrera, Manuel; Sánchez, Rosa María Galán; Laguna, Juan C.; Ciudad, Carlos J.; Alegret, Marta

doi:10.1016/j.bbrc.2004.04.021

Cited by 76 publications

(44 citation statements)

References 56 publications

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“…Similar results were obtained in our previous study 15 . These results support the hypothesis that a-FABP could be a contributing factor to the development of hypertriglyceridemia, glucose intolerance and insulin resistance 16 . ASP, a hormone produced by adipocytes, plays an important role in lipid metabolism 17 .…”

Section: Discussionsupporting

confidence: 88%

Potential Markers of Insulin Resistance in Healthy vs Obese and Overweight Subjects

Horáková

Stejskal²,

Pastucha³

et al. 2010

BIOMED PAP

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Background. Insulin resistance can lead to the metabolic syndrome, which may have cardiovascular and metabolic consequences. The study aimed at verifying the serum concentration levels of the adipose tissue proteins adiponectin, adipocyte-fatty acid binding protein (a-FABP) and acylation stimulating protein (ASP), and the potential use of these markers for early diagnosis of insulin resistance.Methods and results. Healthy subjects (Group A, n = 53), overweight subjects (Group B, n = 29) and obese subjects (Group C, n = 51) were studied. Those in Groups B and C had symptoms of insulin resistance. The subjects were selected based on clinical and laboratory findings. The concentrations of adiponectin were highest in the healthy subjects in Group A (14.18 ± 6.99 mg/), lower in the overweight subjects in Group B (11.12 ± 4.46 mg/l) and lowest in the obese subjects in Group C (8.15 ±2.70 mg/l). The a-FABP values were lowest in Group A (20.23 ± 7.95 mg/l), higher in Group B (32.22 ± 15.56 mg/l) and highest in Group C (40.43 ± 23.31 mg/l). The concentrations of ASP were lowest in the Group A healthy subjects (43.01 ± 22.78 nmol/l), higher in the Group B overweight subjects (50.58 ± 25.57 nmol/l) and highest in the Group C obese subjects (54.70 ± 26.41 nmol/l). Statistically significant correlation coefficients in subjects from all groups among the markers studied describe the highest correlation is between a-FABP and BMI (r = 0.48), adiponectin and QUICKI (r = 0.42), adiponectin and triacylglycerols (r = -0.35), ASP and BMI (r = 0.33) and adiponectin and BMI (r = -0.31).Conclusions. The concentrations of all studied markers were different in the healthy subjects as compared to the overweight or obese ones. Adiponectin proved to be a good indicator of insulin sensitivity, the low concentration of which could signal the initial stage of insulin resistance. A-FABP proved to be a prominent marker of "adiposity" in association with the development of insulin resistance. ASP did not prove to show significant differences between the overweight and healthy subjects, but significant differences were found between the obese and healthy subject.

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Section: Discussionsupporting

confidence: 88%

Potential Markers of Insulin Resistance in Healthy vs Obese and Overweight Subjects

Horáková

Stejskal²,

Pastucha³

et al. 2010

BIOMED PAP

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“…All [81][82][83] except one [84] published studies have demonstrated that the serum AFABP level is reduced following successful weight reduction through lifestyle or surgical measures. Furthermore, atorvastatin treatment over 3 months has been found to significantly decrease circulating AFABP levels in statin-naive participants with atherosclerosis [85], in agreement with in vitro findings [57]. In summary, interventional studies suggest that circulating AFABP decreases after weight loss and statin therapy, and might contribute to the beneficial effects of these interventions.…”

Section: Controlssupporting

confidence: 69%

“…Various studies agree that AFABP synthesis is localised in macrophages in atherosclerotic plaques [54][55][56]. Moreover, atorvastatin, which has antiatherogenic properties, potently reduces Afabp mRNA and AFABP protein level in oxLDL-treated human macrophages [57].…”

Section: The Role Of Afabp In the Pathogenesis Of Atherosclerosismentioning

confidence: 91%

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

2012

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Adipocyte fatty acid binding protein (AFABP, also known as aP2 and FABP4) has recently been introduced as a novel fat-derived circulating protein. AFABP serum concentrations are positively correlated with markers of the metabolic syndrome and vascular disease in various cross-sectional and interventional studies. Furthermore, a small set of prospective studies indicates that high AFABP serum levels at baseline predict the risk for metabolic and vascular morbidity and mortality. Studies in Afabp (also known as Fabp4) knockout mice and AFABP inhibitortreated animals suggest that total AFABP promotes insulin resistance, hypertriacylglycerolaemia and atherosclerosis by ligand/ligand delivery, as well as ligand-independent mechanisms. In contrast, the pathophysiological significance of circulating AFABP and the mechanisms leading to its release remain to be established. The current review summarises recent findings on the regulation and potential role of AFABP in metabolic and vascular disease.

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“…It is also detected in activated macrophages, and aP2 level is elevated in human atherosclerotic lesions. Interestingly, aP2 expression in macrophages is negatively regulated by statins (20). As directly shown in mice models, reduction in aP2 abundance is metabolically beneficial; if similar in humans then alleles that reduce aP2 expression or activity might confer resistance to some or all of these parameters in humans.…”

Section: Discussionmentioning

confidence: 86%

A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease

Tuncman

Erbay

Hom

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

264

198

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Obesity and the associated pathologies including dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular disease constitute a major threat to global human health. Yet, the genetic factors that differentially predispose individuals to this cluster of pathologies are unclear. The fatty acid-binding protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and macrophages. Mice with aP2 deficiency are partially resistant to obesityinduced insulin resistance and type 2 diabetes, have lower circulating triglycerides, and exhibit marked protection against atherosclerosis. Here, we demonstrate a functionally significant genetic variation at the aP2 locus in humans that results in decreased adipose tissue aP2 expression due to alteration of the CAAT box͞enhancer-binding protein binding and reduced transcriptional activity of the aP2 promoter. In population genetic studies with 7,899 participants, individuals that carry this T-87C polymorphism had lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes compared with subjects homozygous for the WT allele. Taken together, our results indicate that reduction in aP2 activity in humans generate a metabolically favorable phenotype that is similar to aP2 deficiency in experimental models.adipocyte ͉ FABP4 ͉ triglyceride ͉ macrophage ͉ metabolic syndrome

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Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages

Cited by 76 publications

References 56 publications

Potential Markers of Insulin Resistance in Healthy vs Obese and Overweight Subjects

Potential Markers of Insulin Resistance in Healthy vs Obese and Overweight Subjects

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease

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