Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia

Martínez-Hervás, Sergio; Artero, Ana; Martinez‐Ibañez, Juncal; Tormos, M. Carmen; González-Navarro, Herminia; Priego, Antonia; Martínez-Valls, José Francisco; Sáez, Guillermo; Real, José T.; Carmena, Rafael; Ascaso, Juan F.

doi:10.1111/eci.12642

Cited by 5 publications

(4 citation statements)

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“…This could be partly explained by the chronic proinflammatory state and increased oxidative stress that has been observed in FCH subjects, particularly those with insulin resistance. 4 9 10 In the present study, we have observed that, compared with controls, FCH subjects have increased MPO and PAI-1 blood values. The elevation of these two proinflammatory and proatherothrombotic biomarkers was significantly higher in the presence of insulin resistance.…”

Section: Discussionsupporting

confidence: 59%

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

Carratalá¹,

Martínez-Hervás

Rodríguez-Borja³

et al. 2018

Journal of Investigative Medicine

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Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (IMT) was measured by the same investigator by standardized protocol. No differences in age, body mass index (BMI) or waist circumference were observed between the two groups. HOMA and PAI-1 values were higher in the FCH group, reaching statistical significance in those subjects with insulin resistance. In addition, PAI-1 values correlated significantly with metabolic syndrome components and carotid IMT. It is known that the elevated cardiovascular risk that characterizes FCH is frequently associated with insulin resistance. We have detected that two known proinflammatory and proatherothrombotic factors (MPO and PAI-1) are significantly elevated in FCH subjects with insulin resistance. These results could partly explain the high cardiovascular risk present in FCH subjects.

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Section: Discussionsupporting

confidence: 59%

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

Carratalá¹,

Martínez-Hervás

Rodríguez-Borja³

et al. 2018

Journal of Investigative Medicine

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“…In FCHL, there is an upregulation of thioredoxins, which are disulfide reductases responsible for regulating redox reactions, and confers an increased oxidative stress with reduced glutathione levels associated to IR. Both the increase in oxidative stress damage and IR contribute to atherosclerosis and potentially to increased cardiovascular risk in FCHL patients 38 . Most FCHL patients have increased sdLDL and apoB levels for all levels of IR in comparison to controls, adjusted by HOMA-IR and BMI 9 ; this supports the concept that the etiology of the lipid phenotype in FCHL is a result of additive effects of genetic determinants with modulation by BMI and IR.…”

Section: Pathophysiology Of Fchlmentioning

confidence: 99%

Familial Combined Hyperlipidemia: Current Knowledge, Perspectives, and Controversies

Bello‐Chavolla¹,

García²,

Ríos-Ríos³

et al. 2018

RIC

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Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of controversy. FCHL is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B. FCHL is an oligogenic primary lipid disorder, which can occur due to the interaction of several contributing variants and mutations along with environmental triggers. Controversies surrounding the relevance of identifying FCHL as a cause of isolated hypertriglyceridemia and a differential diagnosis of familial hyper-triglyceridemia are offset by the description of associations with USF1 and other genetic traits that are unique for FCHL and that are shared with other conditions with similar pathophysiological mechanisms. Patients with FCHL are at an increased risk of cardiovascular disease and mortality and have a high frequency of comorbidity with other metabolic conditions such as type 2 diabetes, non-alcoholic fatty liver disease, steatohepatitis, and the metabolic syndrome. Management usually requires lipid-lowering therapy directed toward reducing cholesterol and triglyceride concentrations along with cardiovascular risk protection. In recent years, the number of research studies on FCHL has been decreasing, mainly due to a lack of recognition of its impact on disease burden and comorbidity and the complexity in identifying probands for studies. This creates areas of opportunity to develop research for FCHL in epidemiology, genetics, pathophysiology, therapeutics, and cardiovascular risk management, which are discussed in depth in this review.

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The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled 'Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure' [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2][3][4][5][6][7].Although cardiac transplantation is recommended in terms of lasting clinical outcomes in patients with advanced refractory heart failure (HF) [8], the lack of organ donors and the ineligibility of some patients imply the need for improving alternative medical and surgical therapeutic strategies.In this retrospective study, the authors assessed clinical outcomes at 24-month follow-up of conservatively vs. surgically treated patients with refractory heart failure (HF) at the Medical University of Vienna. Of the 118 patients enrolled, 50 (42%) were conservatively managed using optimized medical therapy (OMT), while 69 (58%) were treated with the implantation of a ventricular assist device (VAD).

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confidence: 99%

“…The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled 'Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure' [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2][3][4][5][6][7].…”

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confidence: 99%

Advanced refractory heart failure: conservative or interventional approach?

Rigamonti

Montecucco

Liberale

2016

Eur J Clin Investigation

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The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled "Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure" [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2-7]. This article is protected by copyright. All rights reserved

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Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia

Abstract: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.

Cited by 5 publications

References 25 publications

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

Familial Combined Hyperlipidemia: Current Knowledge, Perspectives, and Controversies

Advanced refractory heart failure: conservative or interventional approach?

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