Erythrocyte Lipid Research Articles

Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients.

Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈ 7 years). Primary outcome was defined as cardiovascular-related deaths or new-onset cardio-cerebrovascular events. Cox regression model uncovered plasma/erythrocyte lipids associated with incident cardio-cerebrovascular events in the erythrocyte cohort (n=117 patients, 37 events) and plasma cohort (n= 45 patients, 11 events), respectively. Both the erythrocyte lipid panel [PA 40:5, PI 34:2, PC 42:6, AUC= 0.83] and plasma lipid panel [PC O-34:1, GM3 18:1;O2/25:0, TG 44:1(16:1_28:0), AUC = 0.94] significantly improved the prediction of cardio-cerebrovascular-related outcome compared to the base model comprising age, sex and dialysis vintage alone. Our findings underscore the pathophysiological significance of anionic phospholipid accretion in erythrocytes in the development of cardio-cerebrovascular complications in dialysis patients. In particular, distorted membrane lipid asymmetry leads to compromised membrane deformability, aberrant cell-cell interactions and altered glutathione metabolism in the erythrocytes of high-risk individuals even at relatively early stage of hemodialysis. Our findings thus underscore the importance of maintaining the RBC pool to lower the risk of cardio-cerebrovascular complications in dialysis patients.

Withdrawn: Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients

Age-associated deterioration of physiological functions occur at heterogeneous rates across individual organs. A granular evaluation of systemic metabolic mediators of aging in a healthy human cohort (n = 225) identified prominent increases in circulating uremic toxins that were recapitulated in mice, on which we further characterized the aging phenome across five peripheral organs. Our multi-omics analyses connected systemic aging profiles primarily to kidney metabolism, uncovering a metabolic association between localized glucosylceramide (GluCer) accretion and renal functional decline. Elevated GluCers were also associated with higher risk of deaths in an independent cohort of aged individuals (n = 271). We report GluCer-mTOR signaling commencing at late middle-age that disrupts mitophagy and undermines mitochondrial respiration in kidney. Conserved between human and mice, GluCer-mediated renal dysfunction is female-biased and modulated by intracellular purines. Our work provides molecular basis for the sexually disparate effects of mTOR inhibition on mammalian lifespan, possibly ascribed to the evolutionary cost of female reproduction.

Eco-innovative aquafeeds biofortified with Asparagopsis taxiformis to improve the resilience of farmed white seabream (Diplodus sargus) to marine heatwave events

Extreme weather events, like marine heatwaves (MHWs), are becoming more frequent and severe due to climate change, posing several challenges to marine ecosystems and their services. As disease outbreaks are often prompted by these acute phenomena, it is essential to develop eco-innovative strategies that can efficiently improve farmed fish resilience, especially under sub-optimal rearing conditions, thereby ensuring a sustainable aquaculture production.This study aimed to unveil farmed juvenile white seabream (Diplodus sargus, 28.50 ± 1.10 g weight, n = 150) immune and antioxidant responses under a category II MHW in the Mediterranean Sea (+4 °C, 8 days of temperature increase plus 15 days of plateau at the peak temperature) and to investigate whether a 30 days period of prophylactic biofortification with Asparagopsis taxiformis (1.5 %, 3 % and 6 %) enhanced fish resilience to these extreme events. Several biomarkers from different organization levels (individual, cellular, biochemical and molecular) were assessed upon 30 days of biofortification (T30), exposure (after 8 days of temperature increase + 15 days at peak temperature, T53) and recovery (8 days of temperature decrease, T61) from the MHW.Results showed that MHW negatively affected the fish physiological status and overall well-being, decreasing specific growth rate (SGR) and haematocrit (Ht) and increasing erythrocyte nuclear abnormalities (ENAs) and lipid peroxidation (LPO). These adverse effects were alleviated through biofortification with A. taxiformis. Seaweed inclusion at 1.5 % was the most effective dose to minimize the severity of MHW effects, significantly improving immune responses of D. sargus (i.e. increased levels of immunoglobulin M, peroxidase activity and lysozyme expression) and modulating antioxidant responses (i.e. decreased LPO, catalase and glutathione S-transferase activity). These findings confirm that A. taxiformis is a functional ingredient of added value to the aquaculture industry, as its inclusion in marine fish diets can beneficially modulate fish immunity and resilience under optimal and adverse rearing conditions.

Cardiometabolic assessment through erythrocyte fatty acid profile, cardiometabolic index (CMI), and lipid accumulation product (LAP) in testicular germ-cell tumor survivors

Cardiometabolic assessment through erythrocyte fatty acid profile, cardiometabolic index (CMI), and lipid accumulation product (LAP) in testicular germ-cell tumor survivors

Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis.

BACKGROUNDDisease of the aorta varies from atherosclerosis to aneurysms, with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears, to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience.METHODSIntimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.RESULTSNonhemorrhagic, nonatheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation.CONCLUSIONThese findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function, but even together are not sufficient to induce atherosclerosis.FUNDINGNIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.

Assessment of oxidative stress parameters in summer anestrous buffaloes exhibiting differential fertility following melatonin implants treatment

For evaluating the impact of melatonin implants treatment during non-breeding season to ameliorate oxidative stress, 132 anestrous buffaloes were subcutaneously inserted with 2x4 mm absorbable slow-release melatonin implants (18 mg/50 kg b wt) at the base of left ear and 60 buffaloes were used as control. Ovarian ultrasonography and jugular vein blood sampling were carried out at 7-day interval till day 35 post-treatment or till ovulation, whichever was earlier. Control and implanted buffaloes were subjected to artificial insemination (AI) at overt or induced estrus followed by pregnancy diagnosis at day 90 post-AI. Erythrocytic lipid peroxidation (LPO) values were reduced (P<0.05) in implanted buffaloes from day 21 post-treatment onwards when compared to their pre-treatment and Control group values. However, the concentrations of erythrocytic glutathione peroxidase (GPx), glutathione reductase and superoxide dismutase (SOD) were invariably higher (P<0.05) following treatment as compared to their pre-treatment and Control group values. The buffaloes ovulating in Control or Treatment group revealed higher (P<0.05) erythrocytic GPx in the Latter group. Also, between pregnant counterparts of Control and Treatment group, the Latter group buffaloes exhibited low (P<0.05) erythrocytic LPO, and high (P<0.05) erythrocytic GPx, SOD and catalase. It can be concluded that melatonin implants treatment was successful for mitigating the oxidative stress in summer anestrous buffaloes, and the status of oxidative stress parameters following treatment was better in buffaloes that ovulated or conceived subsequently.

Cardiovascular risk markers (computed tomography‑coronary artery calcium and carotid intima‑media thickness) in patients with rheumatoid arthritis and controls.

Chronic inflammatory diseases, such as arthritis have been linked to a higher risk of developing cardiovascular disease. The present study examined the association between carotid intima-media thickness (CIMT) and coronary artery calcium (CAC), as well as the cardiovascular risk in patients with rheumatoid arthritis (RA). Additionally, the present study used 28 measures to calculate the disease activity score (DAS). To compare healthy controls with patients with RA, a case-control study was conducted that assessed CAC and CIMT in patients with the disease. A total of 45 healthy individuals and 45 patients with a diagnosis of RA were included in the study. With an average age of 50.66±12.35 years, the ages of the participants varied from 24 to 80 years. In both the control and RA patient groups, the sex ratio was 60%. The RA patient group had 53.3% female participants. There were significant variations in the levels of serum urea, potassium, magnesium, serum alkaline phosphatase, serum glutamic pyruvic transaminase, total leucocyte count, erythrocyte sedimentation rate, C-reactive protein (CRP) and lipids [apart from triglycerides and very low-density lipoprotein (VLDL)]. There was a substantial difference in the scores between patients with RA and the controls as regards CAC. A mild-severe risk of coronary artery disease was observed in 55.6% of RA cases and 4.4% of the controls (all mild). Both CIMT thickness and the CAC score exhibited a significant correlation with CRP, serum cholesterol, serum triglycerides, serum low-density lipids and serum VLDL. The DAS of patients ranged between 4.4 and 8.2 (mean, 5.81±0.91). A moderate disease activity was noted in the remaining patients, whereas 66.7% exhibited a high disease activity (DAS >5.2). On the whole, the present study demonstrates that conventional risk factors for cardiovascular disease, such as dyslipidemia, are consistent with both CIMT and CAC. The risk of developing atherosclerosis may be substantially increased by chronic inflammation, as the DAS score corresponds with CIMT and CAC.

Serum opacity factor normalizes erythrocyte morphology in Scarb1−/− mice in an HDL-free cholesterol-dependent way

Compared with WT mice, HDL receptor-deficient (Scarb1−/−) mice have higher plasma levels of free cholesterol (FC)-rich HDL and exhibit multiple pathologies associated with a high mol% FC in ovaries, platelets, and erythrocytes, which are reversed by lowering HDL. Bacterial serum opacity factor (SOF) catalyzes the opacification of plasma by targeting and quantitatively converting HDL to neo HDL (HDL remnant), a cholesterol ester-rich microemulsion, and lipid-free APOA1. SOF delivery with an adeno-associated virus (AAVSOF) constitutively lowers plasma HDL-FC and reverses female infertility in Scarb1−/− mice in an HDL-dependent way. We tested whether AAVSOF delivery to Scarb1−/− mice will normalize erythrocyte morphology in an HDL-FC-dependent way. We determined erythrocyte morphology and FC content (mol%) in three groups—WT, untreated Scarb1−/− (control), and Scarb1−/− mice receiving AAVSOF—and correlated these with their respective HDL-mol% FC. Plasma-, HDL-, and tissue-lipid compositions were also determined. Plasma- and HDL-mol% FC positively correlated across all groups. Among Scarb1−/− mice, AAVSOF treatment normalized reticulocyte number, erythrocyte morphology, and erythrocyte-mol% FC. Erythrocyte-mol% FC positively correlated with HDL-mol% FC and with both the number of reticulocytes and abnormal erythrocytes. AAVSOF treatment also reduced FC of extravascular tissues to a lesser extent. HDL-FC spontaneously transfers from plasma HDL to cell membranes. AAVSOF treatment lowers erythrocyte-FC and normalizes erythrocyte morphology and lipid composition by reducing HDL-mol% FC.

Relation of erythrocyte sedimentation rate, glycemic parameters and lipid profile for the prediction of major adverse cardiovascular events: A single-center, cross-sectional study in Palestine

Relation of erythrocyte sedimentation rate, glycemic parameters and lipid profile for the prediction of major adverse cardiovascular events: A single-center, cross-sectional study in Palestine

Resolution of Sickle Cell Crisis Following Administration of Amiodarone.

Prior studies support a link between erythrocyte sickling and membrane lipid composition.Amiodarone may impact erythrocyte pathophysiology by increasing cellular lipids including bis(mono)acylglycerol phosphate (BMP).Drugs with effects on erythrocyte lipid fractions may be beneficial during sickle cell crises.

Abstract 406: Normalization Of Erythrocyte Morphology In Scarb1 -/- Mice By Bacterial Serum Opacity Factor Is Dependent On HDL-free Cholesterol

Compared to wild-type mice, HDL-receptor-deficient (Scarb1 -/- ) mice have higher plasma levels of free cholesterol (FC)-rich HDL and exhibit multiple pathologies—female infertility and deranged platelet and erythrocyte morphology and function. These pathologies are associated with a low mol% FC in ovaries, platelets, and erythrocytes, effects that are reversed by the HDL-lowering drug probucol. Some strains of Streptococcus pyogenes secrete a protein, serum opacity factor (SOF), which catalyzes the clouding i.e., opacification, of plasma. SOF specifically targets and quantitatively converts HDL into three products, that include a cholesteryl ester-rich microemulsion containing all the cholesterol content of >100,000 HDL particles as well as APOE and its heterodimer with APOA2 as its sole apolipoproteins. Delivery of SOF with an adeno-associated virus (AAV SOF ) constitutively lowers plasma HDL-FC and reverses female infertility in Scarb1 -/- mice. Thus, we tested the hypothesis—AAV SOF delivery to Scarb1 -/- mice will normalize erythrocyte morphology in an HDL-FC dependent way. The erythrocyte morphology and FC content expressed as mol% FC of three groups of mice—WT, untreated Scarb1 -/- mice (control) and Scarb1 -/- mice receiving AAV SOF —were compared and correlated with their respective HDL-mol% FC. Among Scarb1 -/- mice, AAV SOF treatment normalized reticulocyte number, erythrocyte morphology and erythrocyte mol% FC. Plasma- and HDL-mol% FC positively correlated (p < 0.0001) across all three groups of mice. HDL-mol% FC also positively correlated with erythrocyte mol% FC (p < 0.0001). Finally, the erythrocyte mol% FC positively correlated with both the number of reticulocytes (p = 0.006) and abnormal erythrocytes (p < 0.0001). Although less profound, AAV SOF treatment also reduced the FC contents of some extravascular tissues. HDL-FC spontaneously transfers from plasma lipoproteins to cell membranes in multiple tissues sites on a time scale of minutes to a few hours. FC-enrichment of erythrocytes, which are in contact with plasma HDL, was more profound than FC enrichment in tissues. AAV SOF treatment lowers both plasma HDL-FC and erythrocyte-FC and normalizes erythrocyte morphology and lipid composition in an HDL-FC dependent way.

A-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy.

It is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that disturbed α-Synuclein homeostasis is the link between Gaucher disease and Parkinson's disease. The pathogenic mechanism linking these entities is still a topic of debate and both gain- and loss-of-function theories have been put forward, which however are not mutually exclusive. In the present study we expanded our previous studies to include not only Gaucher disease patients but also Gaucher disease carriers and Gaucher disease patients following Enzyme Replacement Therapy. In these groups we investigated α-Synuclein in red blood cell membranes in association with lipid abnormalities described in Gaucher disease. These included glucosylceramide and its species, glucosylsphingosine, glucosylcholesterol and plasmalogens. Increased oligomerization of α-Synuclein in red blood cell membranes was observed not only in Gaucher disease patients but also in carriers of the disease. There were no qualitative differences in the lipids identified in the groups studied. However, significant quantitative differences compared to controls were observed in Gaucher disease patients but not in Gaucher disease carriers. Enzyme Replacement Therapy reversed the biochemical defects and normalized α-Synuclein homeostasis, providing for the first time evidence in human subjects that such homeostatic dysregulation is reversible. Further studies investigating α-Synuclein status during the differentiation of erythroid progenitors could provide new data on the pathogenic mechanism of α-Synuclein oligomerization in this system.

Efficacy of Siwan Traditional Therapy on Erythrocyte Sedimentation Rate, Lipid Profile, and Atherogenic Index as Cardiac Risk Factors Related to Rheumatoid Arthritis.

Background and Objectives: The most frequent cause of mortality in rheumatoid arthritis (RA) patients is cardiovascular disease (CVD). Inflammation, dyslipidemia, and decreased physical activity are some of the main risk factors for CVD. Siwan sand therapy is a type of traditional therapy used in Egypt to treat RA. The approach of this therapy depends on the experience of the healers. The aim of the current study was to compare the effects of three sessions of Siwan traditional therapy to five sessions on common CVD risk factors and physical function in rheumatoid arthritis patients. Materials and Methods: Thirty patients (9 male and 21 female) were assigned into two groups of equal size: group (A) received three sessions of Siwan traditional therapy in the form of a sand bath. Group (B) received the same form of therapy for five days. Erythrocyte sedimentation rate (ESR), lipid profile, atherogenic index of plasma (AIP), and a health assessment questionnaire (HAQ) were measured before and after treatment. Results: There was a significant increase above normal within group (A) for ESR (p = 0.001), triglycerides (TG; p = 0.015), total cholesterol (Tot-Chol; p = 0.0001), and low-density lipoprotein (LDL; p = 0.0001). However, there were no considerable differences in high-density lipoprotein (HDL; p = 0.106), very low-density lipoprotein (VLDL; p = 0.213), AIP (p = 0.648), and HAQ (p = 0.875). For the second group, there were significant changes within group B only in Tot-Chol (p = 0.0001), HDL (p = 0.0001), VLDL (p = 0.0001), AIP (p = 0.008), and HAQ (p = 0.014). There was a significant difference between both groups regarding HDL (p = 0.027), LDL (p = 0.005), AIP (p = 0.029), ESR (p = 0.016), and HAQ (p = 0.036). Conclusions: For RA patients, five days of Siwan traditional therapy caused significant changes regarding inflammation, Tot-Chol, LDL, HDL, AIP, and functional activity when compared to three days of Siwan hot sand therapy.

Correlation between Mild Cognitive Impairment and Sarcopenia: The Prospective Role of Lipids and Basal Metabolic Rate in the Link.

There is evidence of correlation between mild cognitive impairment (MCI) and sarcopenia (SA). However, the influencing factors and the mechanism, such as age-related lipid redistribution, remain unknown. This study aimed to clarify the role of dietary fats and erythrocyte lipids profile combined with basal metabolic rate (BMR) in the link between MCI and SA. A total of 1050 participants aged 65 to 85 were divided into control, MCI, SA and MCI and SA groups. Bioelectrical impedance analysis was used to evaluate appendicular lean mass and BMR. Cognition and dietary nutrition were detected by neuropsychological tests and food frequency questionnaires. UHPLC-QExactive-MS/MS and UHPLC-Qtrap-MS/MS were used to conduct the lipidomics analysis. Lower dietary intake of different phospholipids, unsaturated fatty acids and kinds of choline were significantly associated with MCI and SA. Least absolute shrinkage and selection operator, multivariate logistic regression, receiver operating characteristic curve and validation tests provided evidence that specific phospholipids, unsaturated fatty acids and BMR might be the critical factors in the processing of MCI and SA, as well as in their link. The lipidomic analysis observed a clear discrimination of the lipid profiles in the individuals who are in MCI, SA, or MCI and SA, compared with the control. Lower expressions in certain phospholipid species, such as sphingomyelin and phosphatidylethanolamines, decreased phosphatidylcholine with more unsaturated double bonds, lower level of lipids with C20:5 and C20:4, higher level of lipids with C18:2 and lipids with a remodeled length of acyl chain, might be closely related to the link between MCI and SA. Inadequate dietary intake and lower concentrations of the erythrocyte lipid profile of phospholipids and unsaturated fatty acids with a lower level of BMR might be the key points that lead to progress in MCI and SA, as well as in their link. They could be used as the prospective biomarkers for the higher risk of cognitive decline and/or SA in elderly population.

Green Synthesis of Silver Nanoparticles Using Spilanthes acmella Leaf Extract and its Antioxidant-Mediated Ameliorative Activity against Doxorubicin-Induced Toxicity in Dalton's Lymphoma Ascites (DLA)-Bearing Mice.

Green synthesis of metal nanoparticles is a rapidly growing research area in the field of nanotechnology because of their biomedical applications. This study describes the synthesis of silver nanoparticles (AgNPs) using Spilanthes acmella leaf extract and its ameliorative effects against doxorubicin-induced toxicity. The formation of AgNPs was confirmed by a ultraviolet-visible (UV-vis) spectrum that revealed an absorption band at 430 nm. A shift in the absorption bands in Fourier-transform infrared spectroscopy (FT-IR) confirmed the bioactive molecules of S. acmella leaf extract that acted as a reducing and capping agent. The spherical shape of AgNPs was confirmed by scanning electron microscope (SEM) analysis, and the presence of elemental silver was indicated by energy dispersive X-ray spectroscopy (EDS) analysis. X-ray diffraction (XRD) analysis revealed that the crystalline size of the synthesized AgNPs was 6.702 nm. Treatment of Dalton's lymphoma ascites (DLA) mice with 20 mg/kg of doxorubicin (DOX) significantly increased the activities of serum toxicity markers including aspartate amino-transferase (AST), alanine amino-transferase (ALT), and lactate dehydrogenase (LDH). However, compared to DOX alone treatment, the coadministration of DOX and AgNPs reduced AST, ALT, and LDH activities. DOX alone treatment reduced glutathione (GSH) contents and decreased the activities of glutathione-s-transferase (GST) and superoxide dismutase (SOD) in DLA mice. However, the administration of AgNPs to DOX-treated DLA mice increased GSH content and the activities of GST and SOD. Consistently, biosynthesized AgNPs were found to possess significantly higher free-radical scavenging activities when compared to the S. acmella leaf extract, as measured by ABTS, DPPH, and O2 •- assays. The biosynthesized AgNPs also showed significant inhibitory activities against erythrocyte hemolysis and lipid peroxidation in the liver homogenate.

Erythrocyte Membrane Docosahexaenoic Acid (DHA) and Lipid Profile in Preterm Infants at Birth and Over the First Month of Life: A Comparative Study with Infants at Term.

An observational comparative study was designed to assess the fatty acids profile in erythrocyte membrane phospholipids of 30 preterm neonates (<32 weeks gestation) at birth and after 1 month of life versus a convenience sample of 10 infants born at term. The panel of fatty acids included the families and components of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (PUFAs) as well as enzyme activity indexes and fatty acids ratios. At birth, the comparison of fatty acid families between preterm and term neonates showed a significantly higher content of SFAs and n-6 PUFAs, and a significantly lower content of MUFAs and n-3 PUFAs in the preterm group. After 30 days of life, significantly higher levels of n-6 PUFAs and significantly lower levels of n-3 PUFAs among preterm neonates persisted. At 30 days of birth, n-6 PUFA/n-3 PUFA and arachidonic acid (ARA) ARA/DHA remained significantly elevated, and DHA sufficiency index significantly decreased in the preterm group. The pattern of n-3 PUFA deficiency at birth and sustained for the first month of life would support the need of milk banking fortified with DHA and the use of DHA supplementation in breastfeeding mothers.

Proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis: A marker of disease activity and severe disease manifestations with potential therapeutic implementations.

This study aims to investigate proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis (d-SSc) and its relation to disease activity, severity and subclinical atherosclerosis in such group of patients. Between December 2019 and July 2021, a total of 41 patients with d-SSc (17 males, 24 females; mean age: 36.1±1.9 years; range, 19 to 58 years) and 41- age and sex-matched healthy controls (17 males, 24 females; mean age: 40.1±1.7 years; range, 20 to 60 years) were included. Disease activity and skin thickness of the patients were evaluated using the European Scleroderma Study Group (EScSG) score and modified Rodnan skin score (mRSS), respectively. Serum PCSK9 and carotid intima-media thickness (CIMT) were measured using enzyme-linked immunosorbent assay (ELISA) and Duplex ultrasound, respectively. Serum PCSK9 was higher in patients compared to controls (p=0.003), particularly in those with digital ulcer (DU) and interstitial lung disease (ILD) (p<0.001). The PCSK9 positively correlated with the mean pulmonary artery pressure, EScSG, mRSS, C-reactive protein (p<0.001), erythrocyte sedimentation rate (p<0.05), lipid profile, and mean CIMT (p<0.01). In the multivariate analysis, EScSG, mRSS, lipid profile, and waist circumference were significantly correlated with PCSK9. Serum PCSK9 levels of (182.6 ng/mL) had 77.7% sensitivity and 81.2% specificity for diagnosing DU versus (172.8 ng/mL) 90.1% and 73.5% for ILD (p<0.001). Serum PCSK9 is upregulated in d-SSc with higher levels in severe disease manifestations such as DU and ILD. It is correlated well with disease activity, more severe disease manifestations, and CIMT. The PCSK9 inhibitors may be a target of therapy in diseases with premature atherosclerosis such as d-SSc regardless of its anti-cholesterol effect, at least in more severe manifestations.

Association of soluble cell adhesion molecules and lipid levels in rheumatoid arthritis patients.

To evaluate the relationship between soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and lipid levels in rheumatoid arthritis (RA) patients with and without carotid plaque (CP). Cross-sectional study nested of a RA cohort. RA patients without a previous cardiovascular event or statins' therapy, aged 40-75years were recruited at an outpatient cardio-rheumatology clinic. Carotid ultrasound was performed in all study subjects. RA patients with CP were included and matched to RA patients without CP by age, gender, and traditional cardiovascular risk factors. Blood samples were drawn at the time of recruitment to measure sVCAM-1, sICAM-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid levels. Correlations between cell adhesion molecules, disease activity indexes, ESR and CRP with lipid levels were assessed with Spearman's correlation coefficient (rs). We included 71 RA patients, 37 with CP and 34 without CP. RA (n = 71) patients had a moderate negative correlation of sVCAM-1 with total cholesterol (TC) (rs = - 0.366, p = 0.002) and low-density lipoprotein (LDL) (rs = - 0.316, p = 0.007), and a small negative correlation with high-density lipoprotein (rs = - 0.250, p = 0.036). ESR showed a small negative correlation with LDL (rs = - 0.247, p = 0.038). Patients with CP had a moderate negative correlation between sVCAM and TC (rs = - 0.405, p = 0.013). Patients without CP showed a moderate negative correlation between sVCAM with TC (rs = - 0.364, p = 0.034) and LDL (rs = - 0.352, p = 0.041), and sICAM with VLDL (rs = - 0.343, p = 0.047). RA patients showed an inverse association of sVCAM-1 and lipid levels. More studies are needed to define the precise role of sVCAM-1 in the lipid paradox of RA.

Amiodarone improves anemia in a murine model of sickle cell disease and is associated with increased erythrocyte bis(monoacylglycerol) phosphate

Sickle cell disease (SCD) is associated with altered plasma and erythrocyte lipid profiles. In a previous study, SCD mice with deficiency of proprotein convertase subtilisin/kexin type 9 (PCSK9) were observed to have more severe anemia and increased sickling compared to control SCD mice. Although PCSK9 affects circulating low density lipoprotein (LDL) by regulation of the LDL receptor, the effect of PCSK9 on anemia was independent of LDL receptor expression. In the current study, erythrocyte metabolomics were performed and revealed altered erythrocyte lipid species between SCD mice with and without PCSK9. Of particular interest, the late endosome-specific lipid bis(mono)acylglycerol phosphate (BMP) 44:12 was markedly decreased in erythrocytes from SCD mice deficient in PCSK9 mice relative to control SCD mice. Incubation of sickle erythrocytes with a neutralizing antibody to BMP increased erythrocyte sickling in vitro. In vitro treatment of SCD erythrocytes with amiodarone (1.5 μM) or medroxyprogesterone (6.75 μM), two pharmacologic compounds known to increase BMP, resulted in reduced erythrocyte sickling. Treatment of SCD mice with amiodarone (10 mg/kg) for 2 weeks resulted in increased BMP, improvement in anemia with reduced reticulocytosis, and decreased ex vivo sickling. In conclusion, severity of anemia in SCD is improved with amiodarone treatment, an effect which may be mediated through increased erythrocyte BMP.

Ailevi Akdeniz Ateşi olan erişkin hastalarda koroner arter hastalığının belirteci olarak epikardiyal yağ doku kalınlığının değerlendirilmesi

Amaç: Ailevi Akdeniz Ateşi (FMF), ataklar halinde giden kronik otoinflamatuvar bir hastalıktır. Ataklar arası dönemde subklinik düzeyde inflamasyonun devam etmesi nedeniyle bu hastalarda artmış ateroskleroz riski mevcuttur. Epikardiyal yağ doku yeni bir kardiyometabolik risk faktörü olup aterosklerotik riskin belirlenmesinde kullanılmaktadır.&#x0D; Bu çalışmanın amacı FMF tanısı ile takip edilen erişkin hastalarda epikardiyal yağ doku kalınlığının ölçülmesi ve subklinik aterosklerotik hastalık riskinin değerlendirilmesidir.&#x0D; Gereç ve yöntemler: Tel-Hashomer kriterlerine göre tanı almış 18 yaş ve üzeri FMF hastası ile yaş ve cinsiyet uyumlu sağlıklı kontrol bu kesitsel çalışmaya dahil edilmiştir. Hastalık özellikleri, FMF gen mutasyonları ve eritrosit sedimentasyon hızı, C-reaktif protein, serum amiloid-A, fibrinojen, lipid düzeyleri ve tam kan sayımları çalışmaya dahil edilme esnasında kaydedilmiştir. Epikardiyal yağ doku kalınlığı, iki boyutlu transtorasik ekokardiyografi ile ölçülmüştür. P değeri