Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery

Bermúdez, Beatriz; López, Sergio; Pacheco, Yolanda M.; Villar, José R.; Muriana, Francisco J. G.; Hoheisel, Jöerg; Bauer, Andrea S.; Abia, Rocı́o

doi:10.1093/cvr/cvn082

Cited by 71 publications

(60 citation statements)

References 29 publications

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“…However, its biological character and current knowledge about its effects in humans suggested that it might play an important role in the development and progression of inflammatory and atherosclerotic Table 4 Relationships of serum macrophage inhibitory cytokine-1 (MIC-1; pg/ml) with other anthropometric, hormonal, and biochemical parameters calculated in a combined population of all three study groups (A, nZ54) and in the combined group of obese patients (B and C, nZ31) both before and after very low calorie diet program (VLCD). processes and cancer (7,10,12). Recent data indicated a direct role for MIC-1 in energy homeostasis regulation in cachectic conditions making it a potentially interesting candidate molecule to modulate food intake and/or body adiposity (14).…”

Section: Discussionmentioning

confidence: 99%

“…MIC-1 was also identified as a predictor of cardiovascular events in a cohort of previously healthy women (11,12) and as an early mediator of the injury response in kidney and lung (13). Recently, a key role of increased MIC-1 concentrations in the induction of cancer-related anorexia and weight loss in animals and humans was described (14).…”

Section: Introductionmentioning

confidence: 99%

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Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Dostálová

Roubíček²,

Bartlova³

et al. 2009

European Journal of Endocrinology

148

140

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Objective: Macrophage inhibitory cytokine-1 (MIC-1) is a novel regulator of energy homeostasis. We explored whether alterations in MIC-1 levels contribute to metabolic disturbances in patients with obesity and/or obesity and type 2 diabetes mellitus (T2DM). Design: We measured serum MIC-1 levels and its mRNA expression in subcutaneous and visceral adipose tissue of 17 obese nondiabetic women, 14 obese women with T2DM and 23 healthy lean women. We also explored the relationship of MIC-1 with anthropometric and biochemical parameters and studied the influence of 2-week very low calorie diet (VLCD) on serum MIC-1 levels. Methods: Serum MIC-1 levels were measured by ELISA and its mRNA expression was determined by RT-PCR. Results: Both obese and T2DM group had significantly elevated serum MIC-1 levels relative to controls. T2DM group had significantly higher serum MIC-1 levels relative to obese group. Serum MIC-1 positively correlated with body weight, body fat, and serum levels of triglycerides, glucose, HbAlc, and C-reactive protein and it was inversely related to serum high-density lipoprotein cholesterol. Fat mRNA MIC-1 expression did not significantly differ between lean and obese women but it was significantly higher in subcutaneous than in visceral fat in both groups. VLCD significantly increased serum MIC-1 levels in obese but not T2DM group. Conclusion: Elevated MIC-1 levels in patients with obesity are further increased by the presence of T2DM. We suggest that in contrast to patients with cancer cachexia, increased MIC-1 levels in obese patients and diabetic patients do not induce weight loss.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Dostálová

Roubíček²,

Bartlova³

et al. 2009

European Journal of Endocrinology

148

140

View full text Add to dashboard Cite

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“…Other cardiovascular cell types, including endothelial cells, vascular smooth muscle cells, and adipocytes, have been shown to produce GDF-15 under stressful conditions. [12][13][14] Moreover, GDF-15 has been detected in atherosclerotic plaque macrophages, where it may be induced by oxidized low-density lipoprotein and proinflammatory cytokines. 3,6 Accumulating evidence indicates that circulating levels of GDF-15 are associated with prognosis in patients with cardiovascular disease.…”

Section: Clinical Perspective On P 1395mentioning

confidence: 99%

Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure

et al. 2010

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Background-Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure. Methods and Results-The circulating concentration of GDF-15 was measured at baseline (nϭ1734) and at 12 months (nϭ1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT). GDF-15 levels at baseline ranged from 259 to 25 637 ng/L and were abnormally high (Ͼ1200 ng/L) in 85% of patients. Higher levels were associated with features of worse heart failure and biomarkers of neurohormonal activation, inflammation, myocyte injury, and renal dysfunction. Baseline GDF-15 levels (per 100 ng/L) were associated with the risks of mortality (hazard ratio, 1.017; 95% confidence interval, 1.014 to 1.019; PϽ0.001) and first morbid event (hazard ratio, 1.020; 95% confidence interval, 1.017 to 1.023; PϽ0.001). In a comprehensive multiple-variable Cox regression model that included clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T, GDF-15 remained independently associated with mortality (hazard ratio, 1.007; 95% confidence interval, 1.001 to 1.014; Pϭ0.02) but not first morbid event. At 12 months, the GDF-15 levels had increased by a similar amount in the placebo and valsartan groups (Pϭ0.94). Increases in GDF-15 over 12 months were independently associated with the risks of future mortality and first morbid event also after adjustment for clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T and their changes. Conclusions-GDF-15 reflects information from several pathological pathways and provides independent prognostic information in heart failure. GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT. (Circulation. 2010;122:1387-1395.)

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“…Under normal physiologic conditions, GDF15 is weakly expressed by most tissues [8,9]. However, following injury, ischemia, and other forms of oxidative and/or metabolic stress, its production is potently upregulated by a wide range of tissues including activated macrophages, cardiomyocytes, and vascular smooth muscle cells [10,11,12]. In large population-based studies, GDF15 has been associated with endothelial dysfunction, atherosclerosis, left ventricular hypertrophy, and impaired systolic function, independent of cardiovascular risk factors such as inflammatory markers (e.g., C-reactive protein) [13,14].…”

Section: Introductionmentioning

confidence: 99%

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

et al. 2017

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Background/Aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.

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Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery

Abstract: The pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.

Cited by 71 publications

References 29 publications

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

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