Low levels of high density lipoprotein cholesterol in patients with active sarcoidosis1This work was supported by the grant number 95/1039 from Fondo de Investigación Sanitaria, Ministerio Sanidad y Consumo, Madrid, Spain.1

Salazar, Albert; Mañá, Juan; Pintó, Xavier; Argimón, Josep M.; Castiñeiras, M J; Fiol, C.; Pujol, Ramón

doi:10.1016/s0021-9150(97)00198-6

Cited by 15 publications

(6 citation statements)

References 33 publications

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“…Our results indicate that hypoxia preferentially decreases the large HDL2, while bed rest had significant negative effects on the small and dense HDL3. In agreement with our findings, previous studies indicate that short-term bed rest preferentially decreases HDL3 sub-fraction ( Yanagibori et al, 1998 ), while lung inflammatory diseases are associated with decreased HDL2 ( Salazar et al, 1998 ; Kim et al, 2016 ). Clinical studies suggest that both HDL2-C and HDL3-C sub-fractions are inversely associated with the incidence of coronary artery disease ( Camont et al, 2011 ).…”

Section: Discussionsupporting

confidence: 93%

Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity

et al. 2018

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In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude. Following hypoxia, either in bed rest or ambulatory condition, markers of cardiometabolic risk shifted toward a more atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic inflammation, as determined by C-reactive protein and serum amyloid A; (c) increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia additively decreased total HDL and delta-5 desaturase index. In parallel to the pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways, consisting of increased circulating TNF-related apoptosis-inducing ligand (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater in ambulatory conditions (+34 ± 6% and +87 ± 31%, respectively) than in bed rest (+17 ± 7% and +2 ± 27% respectively). Hypoxia-induced cardiometabolic risk is blunted by moderate level of physical activity as compared to bed rest. TRAIL and glutathione redox capacity may contribute to the positive interaction between physical activity and hypoxia.Highlights:– Hypoxia and bed rest activate metabolic and inflammatory markers of atherogenesis.– Hypoxia and physical activity activate selected anti-atherogenic pathways.– Hypoxia and physical activity positive interaction involves TRAIL and glutathione.

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Section: Discussionsupporting

confidence: 93%

Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity

et al. 2018

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“…However, the extent of this pleiotropy may have been previously underestimated, since the polygenic pleiotropy between immune and lipid phenotypes was not identified. Further, several clinical and epidemiological studies have reported an association between blood lipids and individual immune-mediated diseases[ 1 – 5 ]. For example, CD and UC have been associated with low levels of HDL and high levels of LDL cholesterol[ 2 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence suggest a relationship between lipid biology and the immune system. For example, clinical and epidemiological data suggest an association between blood lipid levels and immune-mediated diseases, including Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), psoriasis (PSOR) and sarcoidosis (SARC)[ 1 – 5 ]. In addition to diet and other environmental factors, it is possible that the increased occurrence of dyslipidemia and subsequent atherosclerosis in patients with immune-mediated diseases could reflect genetically determined factors influencing both lipid metabolism and immune-mediated disorders that cannot be elucidated by observational epidemiological and clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms

et al. 2015

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Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

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“…In the pathology of sarcoidosis, alterations in circulating lipid levels are observed, notably the reduction in HDL-cholesterol levels and ApoA1 concentrations [ 104 , 105 , 106 ]. Similarly, several proteins involved in lipid metabolism, including SAA, plastin 2, fatty acid binding protein 4, and annexin A2 [ 107 ], are expressed differently in patients than in controls.…”

Section: In Vivo Modelsmentioning

confidence: 99%

“…Similarly, several proteins involved in lipid metabolism, including SAA, plastin 2, fatty acid binding protein 4, and annexin A2 [ 107 ], are expressed differently in patients than in controls. These alterations in lipid metabolism are possibly related to sarcoidosis pathology itself as well as other co-pathologies observed in sarcoidosis, such as the increasing risk of atherosclerosis in patients with sarcoidosis [ 106 , 108 , 109 ].…”

Section: In Vivo Modelsmentioning

confidence: 99%

Models Contribution to the Understanding of Sarcoidosis Pathogenesis: “Are There Good Models of Sarcoidosis?”

Besnard

Jeny

2020

JCM

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Sarcoidosis is a systemic, granulomatous, and noninfectious disease of unknown etiology. The clinical heterogeneity of the disease (targeted tissue(s), course of the disease, and therapy response) supports the idea that a multiplicity of trigger antigens may be involved. The pathogenesis of sarcoidosis is not yet completely understood, although in recent years, considerable efforts were put to develop novel experimental research models of sarcoidosis. In particular, sarcoidosis patient cells were used within in vitro 3D models to study their characteristics compared to control patients. Likewise, a series of transgenic mouse models were developed to highlight the role of particular signaling pathways in granuloma formation and persistence. The purpose of this review is to put in perspective the contributions of the most recent models in the understanding of sarcoidosis.

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Low levels of high density lipoprotein cholesterol in patients with active sarcoidosis1This work was supported by the grant number 95/1039 from Fondo de Investigación Sanitaria, Ministerio Sanidad y Consumo, Madrid, Spain.1

Cited by 15 publications

References 33 publications

Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity

Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity

Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms

Models Contribution to the Understanding of Sarcoidosis Pathogenesis: “Are There Good Models of Sarcoidosis?”

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