scholarly journals High- density lipoprotein function is abnormal in idiopathic inflammatory myopathies

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3515-3525 ◽  
Author(s):  
Sangmae Sharon Bae ◽  
Yuen Yin Lee ◽  
Ani Shahbazian ◽  
Jennifer Wang ◽  
David Meriwether ◽  
...  
Keyword(s):  
Fatty Acids ◽  
High Density Lipoprotein ◽  
Vascular Endothelium ◽  
Density Lipoprotein ◽  
High Density ◽  
Idiopathic Inflammatory Myopathies ◽  
Healthy Controls ◽  
Inflammatory Myopathies ◽  
Antioxidant Function ◽  
Oxidized Fatty Acids

Abstract Objective Damage to the vascular endothelium is strongly implicated in the pathogenesis of idiopathic inflammatory myopathies (IIM). Normally, high-density lipoprotein (HDL) protects the vascular endothelium from damage from oxidized phospholipids, which accumulate under conditions of oxidative stress. The current work evaluated the antioxidant function of HDL in IIM patients. Methods HDL’s antioxidant function was measured in IIM patients using a cell-free assay, which assesses the ability of isolated patient HDL to inhibit oxidation of low-density lipoproteins and is reported as the HDL inflammatory index (HII). Cholesterol profiles were measured for all patients, and subgroup analysis included assessment of oxidized fatty acids in HDL and plasma MPO activity. A subgroup of IIM patients was compared with healthy controls. Results The antioxidant function of HDL was significantly worse in patients with IIM (n = 95) compared with healthy controls (n = 41) [mean (S.d.) HII 1.12 (0.61) vs 0.82 (0.13), P < 0.0001]. Higher HII associated with higher plasma MPO activity [mean (S.d.) 13.2 (9.1) vs 9.1 (4.6), P = 0.0006] and higher oxidized fatty acids in HDL. Higher 5-hydroxyeicosatetraenoic acid in HDL correlated with worse diffusion capacity in patients with interstitial lung disease (r = −0.58, P = 0.02), and HDL’s antioxidant function was most impaired in patients with autoantibodies against melanoma differentiation-associated protein 5 (MDA5) or anti-synthetase antibodies. In multivariate analysis including 182 IIM patients, higher HII was associated with higher disease activity and DM diagnosis. Conclusion The antioxidant function of HDL is abnormal in IIM patients and may warrant further investigation for its role in propagating microvascular inflammation and damage in this patient population.

Abstract 445: Phospholipid Levels Associated with Specific High-Density Lipoprotein Subfractions Predict Cardiovascular Risk in Young Adults with Type 2 Diabetes

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Amy S Shah ◽  
L J Lu ◽  
Jingyuan Deng ◽  
Lawrence M Dolan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Phospholipid Content ◽  
Healthy Controls ◽  
Carotid Imt ◽  
Early Atherosclerosis

Risk for atherosclerosis is greatly increased in people who have type 2 diabetes (T2D). Because of this, the emerging epidemic of adolescent T2D holds ominous implications for premature cardiovascular disease (CVD). High density lipoprotein cholesterol (HDL-C) represents the body’s natural defense against CVD but its levels are depressed in individuals with T2D. Recent studies indicate HDL exists as distinct subspecies raising the possibility that certain species may be more cardioprotective than others. However, little is known regarding the role of HDL subspecies in T2D, especially in the adolescent population. Thus we sought to evaluate HDL subspecies and determine whether certain subspecies are associated with protection against the development of early atherosclerosis as measured by carotid intima medial thickness (IMT). Healthy controls and youth with T2D were recruited. Whole plasma was analyzed by high-resolution gel filtration chromatography to resolve HDL sized particles and lipids in each fraction were quantitated by colorimetric assay. T-tests were used to evaluate group differences and linear regression models were constructed to determine independent predictors of carotid IMT. Youth with T2D had higher BMI, total cholesterol and lower HDL-C compared to healthy controls, p<0.05. The groups did not differ in LDL-C, triglycerides or BP. Phospholipid distributions of HDL subspecies were found to be shifted in participants with T2D compared to controls (p<0.05). There was a significant inverse correlation between carotid IMT and the phospholipid content of larger HDL subfractions 22-24 (p<0.05) in youth with T2D. Linear models demonstrate HDL fraction 22 was the only independent predictor of carotid IMT while HDL-C, LDL-C, total -C and triglycerides were not significant. These data suggest an altered HDL particle subclass distribution may better predict protection against early atherosclerosis. Thus analyzing the HDL subspecies may be a more powerful approach to assessing cardiovascular risk than the currently accepted standard of HDL-C.

scholarly journals Entry of polyunsaturated fatty acids into the brain: evidence that high-density lipoprotein-induced methylation of phosphatidylethanolamine and phospholipase A2 are involved

1996 ◽  
Vol 316 (3) ◽  
pp. 805-811 ◽  
Author(s):  
Valérie MAGRET ◽  
Latifa ELKHALIL ◽  
Françoise NAZIH-SANDERSON ◽  
Françoise MARTIN ◽  
Jean-Marie BOURRE ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
High Density Lipoprotein ◽  
Phospholipase A2 ◽  
Density Lipoprotein ◽  
Bovine Brain ◽  
High Density ◽  
Close Relationship ◽  
The Brain

The conversion of phosphatidylethanolamine (PE) into phosphatidylcholine (PC) by a sequence of three transmethylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL3) in isolated bovine brain capillary (BBC) membranes. HDL3-induced stimulation of BBC membranes pulsed with [methyl-14C]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC. PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A2 (PLA2), as demonstrated by the accumulation of lysophosphatidylcholine (lyso-PC). When PE containing [14C]arachidonic acid in the sn-2 position ([14C]PAPE) is incorporated into BBC membranes, HDL3 stimulation induces the formation of PMME, PDME, PC and lyso-PC and the release of [14C]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL3 stimulates a PLA2 that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA2 activities depend on a HDL3 concentration in the range 0–50 μg/ml and are strictly dependent on HDL3 binding, because HDL3 modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA2 activation. Moreover, HDL3 prelabelled with [14C]PAPE can stimulate PDME and lyso-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL3 can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL3 binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.

scholarly journals Does high-density lipoprotein protect vascular function in healthy pregnancy?

2016 ◽  
Vol 130 (7) ◽  
pp. 491-497 ◽  
Author(s):  
Wan N. Wan Sulaiman ◽  
Muriel J. Caslake ◽  
Christian Delles ◽  
Helen Karlsson ◽  
Monique T. Mulder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Density Lipoprotein ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Cell Damage ◽  
Density Lipoprotein ◽  
High Density ◽  
Major Protein ◽  
Protective Effects ◽  
In Pregnancy

The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.

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