Hyperlipidemia‐induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters

Stancu, Camelia S.; Carnuta, Mihaela G.; Sanda, Gabriela M.; Toma, Laura; Deleanu, Mariana; Niculescu, Loredan S.; Sasson, Shlomo; Simionescu, Maya; Sima, Anca V.

doi:10.1002/mnfr.201500422

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…This could be due to the different animal models and methods for ginger extract preparation that were used . Our group has previously shown that a high‐fat diet induces the decrease of PPARγ protein expression in the SI . The here reported results evidence for the first time that GIN increases PPARγ gene and protein expression in the SI, a possible explanation for the observed increase of apoA‐I levels.…”

Section: Discussionsupporting

confidence: 55%

“…In addition, plasma MPO/PON1 ratio was suggested as a potential predictor of dysfunctional HDL and an indicator of risk stratification in coronary artery disease patients . We have previously reported that HL causes the decrease of apoA‐I protein in the SI . The novelty of our present results resides in evidencing that HL generates oxidized‐apoA‐I in the SI and that this process is associated with the increase of MPO and the decrease of PON1 protein levels in the tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, many studies have investigated its function as a target organ for the treatment of metabolic disorders and CVD . The SI is involved in the synthesis of HDL components, namely apolipoprotein A‐I (apoA‐I), the main apolipoprotein of HDL particles, paraoxonase 1 (PON1), the enzyme that accounts for HDL antioxidant properties, and myeloperoxidase (MPO), a pro‐oxidant enzyme attached to HDL particles, which is increased under pro‐inflammatory HL conditions . The SI takes part in the biosynthesis of HDL through the interaction between the secreted lipid‐poor apoA‐I and the transmembrane transporter ATP‐binding cassette subfamily A member 1 (ABCA1), by which apoA‐I becomes lipidated .…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that the ginger extract (GIN) reduces the lipids accumulated in the liver of hyperlipidemic hamsters through mechanisms involving the decrease of oxidative and endoplasmic reticulum stress and the enhancement of cholesterol efflux . We chose to investigate these mechanisms in HL hamsters because the lipid metabolism of hamster is similar to the human one …”

Section: Introductionmentioning

confidence: 99%

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Hyperlipidemia Determines Dysfunctional HDL Production and Impedes Cholesterol Efflux in the Small Intestine: Alleviation by Ginger Extract

Barbalata

Deleanu

Carnuta

et al. 2019

Molecular Nutrition Food Res

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Scope To assess the impact of ginger extract (GIN) in stimulating the production of quality HDL and the cholesterol efflux in the small intestine (SI), key processes in the management of hyperlipidemia (HL)‐induced hepatic steatosis, and atherosclerosis. Methods and results Three groups of hamsters are used: (i) N, fed standard diet, (ii) HL, fed high‐fat diet for 21 weeks, and (iii) HL‐GIN, HL treated with GIN for the last 5 weeks of diet. Apolipoprotein A‐I (apoA‐I), malondialdehyde‐apoA‐I (MDA‐apoA‐I), paraoxonase1 (PON1), and myeloperoxidase (MPO) are measured in plasma and SI. ATP‐binding cassette A1 transporter (ABCA1), ABCG5/G8, liver X receptor α/β (LXRα/β), peroxisome proliferator‐activated receptor γ (PPARγ), and sirtuin1 (SIRT1) are assessed in the SI. Results show that in HL plasma, GIN decreases MDA‐apoA‐I, MPO/PON1 ratio and increases HDL‐cholesterol/total cholesterol. In HL‐SI, GIN decreases MDA‐apoA‐I and MPO, increases ApoA‐I, PON1, and ABCA1, and restores cholesterol efflux disturbed by HL (SIRT1‐LXRα/β‐PPARγ‐ABCG8). GIN administration is associated with the reduction of the aortic valves lipid‐deposits. Conclusion In HL conditions, GIN stimulates the functional HDL production by restoring apoA‐I quality and quantity through inhibition of the oxidative stress, and increases cholesterol efflux in the SI. These effects are associated with the restoration of SIRT1‐LXRα/β‐PPARγ pathway.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hyperlipidemia Determines Dysfunctional HDL Production and Impedes Cholesterol Efflux in the Small Intestine: Alleviation by Ginger Extract

Barbalata

Deleanu

Carnuta

et al. 2019

Molecular Nutrition Food Res

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“…Paraoxonase 1 (PON1) is an antioxidant enzyme physically associated with HDL particles, its activity being dependent on the levels of apoAI, apoAII and myeloperoxidase (MPO) in HDL 6 , 7 . PON1 is a Ca 2+ -dependent serum esterase that is synthesized mainly in the liver, but also in the intestine and kidney 14 – 16 . The enzyme has aryl esterase, paraoxonase and lactonase activities, being able to degrade oxidized phospholipids and hydrolyze lactones from lipoproteins and cells 14 .…”

Section: Introductionmentioning

confidence: 99%

Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients

Carnuta

Stancu

Toma

et al. 2017

Sci Rep

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There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL2 and HDL3 were isolated from CAD patients’ plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL2 or HDL3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL2 and HDL3, 35% augmented apoAII in HDL2, and in HDL3 increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL2 or HDL3 from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15–20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL3 from ACS) and can discriminate between these two groups of CAD patients.

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Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high‐density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus

et al. 2021

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Peripheral artery disease (PAD) is an atherosclerotic disorder affecting arteries of the lower limbs, the major risk factors including dyslipidemia and diabetes mellitus (DM). We aimed to identify alterations of the proteins in high-density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL 2 and HDL 3 were isolated from plasma of PAD patients with/without DM (PAD-DM/PAD) and healthy subjects (N). Apolipoprotein AI (ApoAI), ApoAII, ApoCIII, clusterin (CLU), paraoxonase 1 (PON1), myeloperoxidase (MPO), and ceruloplasmin (CP) were measured in HDL 2 /HDL 3 and plasma. Oxidation and glycation of the analyzed proteins were assessed as malondialdehyde-protein adducts (MDA) and advanced glycation end-products (AGE), respectively. The anti-inflammatory effect of HDL 3 was estimated as its potential to reduce monocyte adhesion to tumor necrosis factor α-activated endothelial cells. We show that in PAD patients compared to N subjects: (i) HDL 2 presented increased levels of MDA-PON1, AGE-PON1, AGE-ApoAI, ApoAII, ApoCIII, and CP levels, and decreased PON1 levels; (ii) HDL 3 had increased levels of MDA-and AGE-CLU and -ApoAI, MDA-PON1, ApoCIII, CLU, MPO, CP, and reduced PON1 levels. All these alterations were exacerbated by DM. These changes were more pronounced in HDL 3 , which had reduced antiinflammatory potential in PAD and became pro-inflammatory in PAD-DM. In PAD patients' plasma, CLU levels and MPO specific activity increased, while PON1 specific activity decreased. In conclusion, HDL function

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Hyperlipidemia‐induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters

Abstract: The fat diet activates the ERS and oxidative stress, decreases LXRβ, PPARγ, and PON1 in the small intestine, liver, and sera of all HL animals, in parallel with the appearance of atherosclerotic lesions in the aortic valves.

Cited by 17 publications

References 36 publications

Hyperlipidemia Determines Dysfunctional HDL Production and Impedes Cholesterol Efflux in the Small Intestine: Alleviation by Ginger Extract

Hyperlipidemia Determines Dysfunctional HDL Production and Impedes Cholesterol Efflux in the Small Intestine: Alleviation by Ginger Extract

Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients

Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high‐density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus

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