The combined utility of myeloperoxidase (MPO) and paraoxonase 1 (PON1) as two important HDL-associated enzymes in coronary artery disease: Which has a stronger predictive role?

Variji, Atena; Shokri, Yasaman; Fallahpour, Samane; Zargari, Mehryar; Bagheri, Babak; Abediankenari, Saeid; Alizadeh, Ahad; Mahrooz, Abdolkarim

doi:10.1016/j.atherosclerosis.2018.11.004

Cited by 35 publications

(22 citation statements)

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“…In the last few decades, the quality and function of HDL became a consistent indicator of CVD risk [17,18]. Under augmented oxidative stress, HDL becomes dysfunctional, presenting an increased number of MPO molecules that replace the PON1 molecules [17,19]. Thus, dysfunctional HDL can no longer protect LDL from oxidation, these alterations being the key risk factors for initiation and progression of the atherosclerotic plaques.Exposure of endothelial cells (EC) to risk factors induces their activation which consists in the production of pro-inflammatory molecules such as selectins (E-selectin, P-selectin, L-selectin), and of adhesion molecules, such as intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion 1 (VCAM-1) promoting monocyte adhesion and their transmigration into the sub-endothelium [20,21].…”

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confidence: 99%

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.In the last decade the scientific researchers turned their attention to phytochemicals, as effective, safe and low-cost natural bioactive compounds for CVD treatment.Dyslipidemia consists of increased blood concentrations of total cholesterol (TC), low density lipoproteins-cholesterol (LDL-C) and/or triglycerides (TG), and decreased high density lipoproteins-cholesterol (HDL-C) [6]. The lipid metabolism is complex and the candidate mechanisms that could generate dyslipidemia include: (i) excessive dietary lipid absorption in the small intestine; (ii) packing of exogenous lipids with cholesterol and fatty acids produced de novo in the liver and their secretion as very low density lipoproteins (VLDL); (iii) hydrolysis of TG from VLDL by lipases and their conversion into LDL, which are taken up by the peripheral tissues through LDL receptor (LDL-R) and scavenger receptors; (iv) diminished production of HDL by the liver and small intestine, thereby decreasing reverse cholesterol transport (RCT) from the peripheral tissues to the liver; (v) lowered excess cholesterol excretion from the liver into gallbladder or to the intestinal lumen through the ATP-binding cassette G5 and G8 transporters (ABCG5/G8) that facilitate trans-intestinal cholesterol efflux (TICE). Dyslipidemia is associated with the accumulation of LDL in the sub-endothelium of the artery wall. At this site, LDL undergoes oxidative modifications (oxLDL) that trigger inflammatory responses, and is taken up by the monocyte-derived macrophages infiltrated in the sub-endothelium which thus become lipid-loaded foam cells, the hallmark of atheroma development [7]. Until now, the most effective lipid-lowering treatment for hyperlipidemic patients was the statin therapy. But recen...

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confidence: 99%

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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“…Low PON1 activity is observed in conditions conducive to oxidative stress, and high levels of reactive oxygen species. Hence the experimental evidence proceeds to suggest that PON1 is a significant player in the development of the disease of the coronary arteries and may lead in novel strategies as a pharmacological, and nutritional to struggle atherosclerosis . Owing to its these effects, paraoxonase enzyme family is a concerning target for pharmacotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Hence the experimental evidence proceeds to suggest that PON1 is a significant player in the development of the disease of the coronary arteries and may lead in novel strategies as a pharmacological, and nutritional to struggle atherosclerosis. [9] Owing to its these effects, paraoxonase enzyme family is a concerning target for pharmacotherapy. Clearly, PON1 may be considered as a new therapeutic target when looking for novel anti-atherogenic agents.…”

Section: Introductionmentioning

confidence: 99%

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors†

Türkeş

2019

Journal of Pharmacy and Pharmacology

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Objectives Proton‐pump inhibitors (PPIs) are drugs commonly utilized by about 7% of adults in the world. Recent researches have shown that there are countless and severe side effects of these drugs. This situation has raised concern among clinicians and patients alike. The purpose of this study is to contribute the novel drug discovery and development technology and toxicology field by researching interactions of PPIs on paraoxonase 1. Methods In this study, the paraoxonase 1 enzyme was purified from human serum by using rapid and straightforward chromatographic techniques. Subsequently, the inhibition effects of pantoprazole, omeprazole, and esomeprazole, PPIs, were investigated on paraoxonase 1. Besides, molecular docking studies were performed to unravel the binding mechanism between the enzyme and drugs. Key findings All drugs showed potent inhibitory activities. IC50 of the drugs values were 54.780 ± 0.524, 86.470 ± 0.818 and 93.390 ± 0.885 mm and Ki constants were found as 39.895 ± 0.005 mm, 70.112 ± 0.010 mm and 78.868 ± 0.008 mm, respectively. The binding scores observed in silico studies were found to agree with the obtained from in‐vitro experimental results. Conclusions We observed that the drugs decreased PON1 activity at low concentrations. The results show that adjusting the dosages of these medications is a crucial case for each patient. The physicians should more carefully interpret whether there is an essential indication before prescribing PPIs and, if there is, to approve the proper dosing for the situation.

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“…In particular, the process of oxidative modification of apoA‐I through malondialdehyde (MDA) and 4‐hydroxy‐2‐nonenal (4‐HNE) action results in the formation of MDA/4‐HNE‐apoA‐I adducts . Dysfunctional HDL is characterized also by a loss of the antioxidant PON1, a gain of the pro‐oxidant MPO activity, and the increase of the attached ceruloplasmin . No data are now available about the quality of apoA‐I produced by the SI exposed to a high‐fat diet.…”

Section: Introductionmentioning

confidence: 99%

“…[12,13] Dysfunctional HDL is characterized also by a loss of the antioxidant PON1, a gain of the pro-oxidant MPO activity, and the increase of the attached ceruloplasmin. [10,14] No data are now available about the quality of apoA-I produced by the SI exposed to a high-fat diet.…”

Section: Introductionmentioning

confidence: 99%

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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The combined utility of myeloperoxidase (MPO) and paraoxonase 1 (PON1) as two important HDL-associated enzymes in coronary artery disease: Which has a stronger predictive role?

Cited by 35 publications

References 35 publications

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors†

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

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