Oxidized and electronegative low-density lipoprotein as potential biomarkers of cardiovascular risk in obese adolescents

Freitas, Maria Camila Pruper de; Fernandez, Diana Gabriela Estevez; Cohen, Daniëlle; Neto, A. M. Figueiredo; Maranhão, Raul C.; Damasceno, Nágila Raquel Teixeira

doi:10.6061/clinics/2018/e189

Cited by 5 publications

(3 citation statements)

References 41 publications

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“…LDL(-) is a pool of all the modified forms of LDL present in blood with inflammatory and apoptotic properties [ 37 , 38 ]. The LDL(-) proportion was increased in adult obese patients, which agrees with previous findings of increased LDL(-) in obese adolescents [ 39 ]. In addition, we demonstrate for the first time that bariatric surgery decreased LDL(-) proportion.…”

Section: Discussionsupporting

confidence: 92%

Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity

Genua

Puig

Miñambres

et al. 2021

JCM

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The effect of bariatric surgery on lipid profile and the qualitative characteristics of lipoproteins was analyzed in morbidly obese subjects. Thirteen obese patients underwent bariatric surgery. Plasma samples were obtained before surgery and at 6 and 12 months after the intervention. Thirteen healthy subjects comprised the control group. Lipid profile, hsCRP, and the composition and functional characteristics of VLDL, LDL, and HDL were assessed. At baseline, plasma from subjects with obesity had more triglycerides, VLDLc, and hsCRP, and less HDLc than the control group. These levels progressively normalized after surgery, although triglyceride and hsCRP levels remained higher than those in the controls. The main differences in lipoprotein composition between the obese subjects and the controls were increased apoE in VLDL, and decreased cholesterol and apoJ and increased apoC-III content in HDL. The pro-/anti-atherogenic properties of LDL and HDL were altered in the subjects with obesity at baseline compared with the controls, presenting smaller LDL particles that are more susceptible to modification and smaller HDL particles with decreased antioxidant capacity. Bariatric surgery normalized the composition of lipoproteins and improved the qualitative characteristics of LDL and HDL. In summary, patients with obesity present multiple alterations in the qualitative properties of lipoproteins compared with healthy subjects. Bariatric surgery reverted most of these alterations.

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Section: Discussionsupporting

confidence: 92%

Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity

Genua

Puig

Miñambres

et al. 2021

JCM

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“…For example, extracellular ceramides in electronegative LDL or extracellular histones. Electronegative LDL is the LDL fraction whose blood levels are elevated in obese people [104]. Electronegative LDL presents a PLC-like activity [105], which is related to high ceramide content.…”

Section: Palmitic Acid Is a Toll-like Receptor Agonistmentioning

confidence: 99%

The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms

2019

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Palmitic acid is a saturated fatty acid whose blood concentration is elevated in obese patients. This causes inflammatory responses, where toll-like receptors (TLR), TLR2 and TLR4, play an important role. Nevertheless, palmitic acid is not only a TLR agonist. In the cell, this fatty acid is converted into phospholipids, diacylglycerol and ceramides. They trigger the activation of various signaling pathways that are common for LPS-mediated TLR4 activation. In particular, metabolic products of palmitic acid affect the activation of various PKCs, ER stress and cause an increase in ROS generation. Thanks to this, palmitic acid also strengthens the TLR4-induced signaling. In this review, we discuss the mechanisms of inflammatory response induced by palmitic acid. In particular, we focus on describing its effect on ER stress and IRE1α, and the mechanisms of NF-κB activation. We also present the mechanisms of inflammasome NLRP3 activation and the effect of palmitic acid on enhanced inflammatory response by increasing the expression of FABP4/aP2. Finally, we focus on the consequences of inflammatory responses, in particular, the effect of TNF-α, IL-1β and IL-6 on insulin resistance. Due to the high importance of macrophages and the production of proinflammatory cytokines by them, this work mainly focuses on these cells.

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“…First of all, a large scale of clinical study must be done to validate the significance of being a novel clinical biomarker. Dr. Sanchez-Quesada and many other study groups published a variety of papers mentioning the clinical prevalence and the pathogenic mechanisms of electronegative LDL [ 103 , 104 , 105 , 106 , 107 , 108 ]. The level difference between patients and controls are comparable, and the atherogenic properties are noticeable.…”

Section: Implication Of L5 Ldlmentioning

confidence: 99%

Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

et al. 2020

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Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

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Oxidized and electronegative low-density lipoprotein as potential biomarkers of cardiovascular risk in obese adolescents

Cited by 5 publications

References 41 publications

Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity

Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity

The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms

Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

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