Early Stages Of Atherosclerosis Research Articles

Anti-inflammatory and Anti-thrombotic Efficacy of Targeted Ultrasound Microbubbles on LPS-induced HUVEC Cells.

The early stage of atherosclerosis (AS) demonstrates a lipid-driven inflammatory cytokine increase. In the present study, we aimed to use ultrasound-targeted microbubble delivery (UTMD) therapy with the Endostar-loaded target microbubbles (MBs) to reduce AS-related inflammatory response. Normal and lipopolysaccharide (LPS) induced human umbilical vein endothelial cells (HUVECs) were placed in a parallel-plate flow chamber. MBs were perfused through the parallel-plate flow chamber to mimic physiological blood flow. Five groups were set up: G1: Negative control (normal HUVECs); G2: LPS control (LPS induced HUVECs); G3: ICAM-1-loaded-MBs (MBi); G4: Endostar-loaded-MBs (MBe) and G5: Endostar-ICAM-1-loaded-MBs (MBei). mRNA expression of inflammatory factors and release of inflammatory cytokines were detected by RT-PCR and ELISA, respectively. After treatment with MBei, the mRNA expression of cell adhesion molecule-1 (CD31) (p=0.004), endothelin-1 (ET-1) (p=0.010), von willebrand factor (vWF) (p=0.018), extracellular regulated protein kinases (ERK) (p=0.046) and nuclear factor kappa B (NF-κB) (p=0.003) were significantly reduced compared to LPS-induced HUVECs. Release of inflammatory cytokines including tissue factor (TF) (p=0.033), tissue factor pathway inhibitor (TF-PI) (p=0.019), ET-1 (p=0.014), vWF (p=0.030) and blood-coagulation factor VIIα (FVIIα) (p=0.000) were also significantly reduced compared to LPS-induced HUVECs. UTMD therapy can inhibit the inflammatory response by reducing atherosclerotic-related inflammatory factors, suggesting a potential treatment at the early-stage of AS.

Functions of Monocytes and Macrophages and the Associated Effective Molecules and Mechanisms at the Early Stage of Atherosclerosis.

This study aimed to explore the functions and possible underlying regulatory molecules and mechanisms of monocytes and macrophages under early atherosclerotic conditions. THP-1-derived monocytes or macrophages were induced by 50 μg/ml oxidized low density lipoprotein (ox-LDL) for 24 hours, and the degree of lipid metabolism and inflammation were determined. In addition, we identified differentially expressed genes, noncoding ribonucleic acids (RNAs), pathways and mechanisms by RNA sequencing, and performed further correlation analysis and molecular expression verification. Monocytes could not form foam cells with oil red O staining directly and had low levels of lipids as determined by total cholesterol and triglycerides assays, cholesterol uptake molecules CD36, the class A macrophage scavenger receptor and lectin-like oxidized low-density lipoprotein receptor-1 and cholesterol efflux molecules ATP binding cassette transporter A1, ATP binding cassette transporter G1 and liver X receptor α, and inflammatory factors, which were markedly different from those in macrophages. Additionally, sequencing data showed obviously differentially expressed genes, microRNAs and long noncoding RNAs in the atherosclerotic group. We identified 15 upregulated and downregulated genes, and 10 biological processes and pathways involved in atherosclerosis. Specifically, fatty acid desaturase 2 and apolipoprotein A1 in the peroxisome proliferator-activated receptor signaling pathway were differentially expressed in stimulated macrophages, whereas no changes were observed in the monocyte groups. Furthermore, correlation analysis showed differential expressed lncRNAs targeting miRNAs and mRNAs, and 24 competing endogenous RNA (ceRNA) networks of long noncoding RNA-microRNA-messenger RNA in early oxidative macrophages. Monocytes did not directly participate in lipid metabolism before differentiation into macrophages at the early stage in vitro. Furthermore, noncoding RNAs and ceRNA networks might play important roles in regulating the lipid metabolism of macrophages at the early stage of atherosclerosis.

Alteration of connexin expression during early stage of atherosclerosis

Background and Aims: Gap junctions are formed by connexin (Cx) molecules. Their involvement in atherogenesis by regulating direct transduction of inflammatory signals have been suggested. In this study, we investigated the contribution of Cx40 and Cx43 to activation of endothelial cells (ECs).

Effect of lipid- based encapsulated docetaxel nanoparticles- mediated B- mode ultrasound- guided focused low- level confocal dual pulse electrohydraulic shock wave therapy accompanied by intravenous methotrexate administration on early stage atherosclerosis

Background and Aims: In atherosclerosis, local inflammation and associated macrophage activity can lead to foam cell- rich plaque formation. In this study, we developed an experimental confocal dual pulse shock wave therapy system, and investigated its effectiveness on foam cells density reduction, wherein diagnostic B- mode ultrasound is combined with sonodynamic therapy system, with a goal of increased safety.

A Microfluidic Model Artery for Studying the Mechanobiology of Endothelial Cells

Recent vascular mechanobiology studies find that endothelial cells (ECs) convert multiple mechanical forces into functional responses in a nonadditive way, suggesting that signaling pathways such as those regulating cytoskeleton may be shared among the processes of converting individual forces. However, previous in vitro EC-culture platforms are inherent with extraneous mechanical components, which may saturate or insufficiently activate the shared signaling pathways and accordingly, may misguide EC mechanobiological responses being investigated. Here, a more physiologically relevant model artery is reported that accurately reproduces most of the mechanical forces found in vivo, which can be individually varied in any combination to pathological levels to achieve diseased states. Arterial geometries of normal and diseased states are also realized. By mimicking mechanical microenvironments of early-stage atherosclerosis, it is demonstrated that the elevated levels of the different types of stress experienced by ECs strongly correlate with the disruption of barrier integrity, suggesting that boundaries of an initial lesion could be sites for efficient disease progression.

Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion

Agomelatine is a non-selective melatonin receptor agonist and an atypical antidepressant with anti-inflammatory, neuroprotective, and cardioprotective effects. The renin-angiotensin system modulates blood pressure and vascular homeostasis. Angiotensin II (Ang II) and its receptor Ang II type I receptor (AT1R) are recognized as contributors to the pathogenesis of cardiovascular and cardiometabolic diseases, including diabetes, obesity, and atherosclerosis. The recruitment and attachment of monocytes to the vascular endothelium is a major event in the early stages of atherosclerosis and other cardiovascular diseases. In the present study, we demonstrate that agomelatine reduced Ang II-induced expression of AT1R while significantly inhibiting the attachment of monocytes to endothelial cells induced by Ang II and mediated by ICAM-1 and VCAM-1. Additionally, Ang II inhibited the expression of the chemokines CXCL1, MCP-1, and CCL5, which are critical in the process of immune cell recruitment and invasion. Agomelatine also suppressed the expression of TNF-α, IL-8, and IL-12, which are proinflammatory cytokines that promote endothelial dysfunction and atherogenesis. Importantly, we demonstrate that the inhibitory effect of agomelatine against the expression of adhesion molecules is mediated through the downregulation of Egr-1 signaling. Together, our findings provide evidence of a novel mechanism of agomelatine that may be practicable in the treatment and prevention of cardiovascular diseases.

Rapid Progression of Coronary Atherosclerosis in Patients Taking an Oral Antitumor, Multikinase Receptor Inhibitor.

Rapid Progression of Coronary Atherosclerosis in Patients Taking an Oral Antitumor, Multikinase Receptor Inhibitor.

Role of Blood Stasis Syndrome of Kampo Medicine in the Early Pathogenic Stage of Atherosclerosis: A Retrospective Cross-Sectional Study.

In Kampo medicine, blood stasis (BS) syndrome is strongly associated with microangiopathy and can lead to atherosclerosis. Vascular endothelial dysfunction (VED), evaluated through flow-mediated dilation (FMD), plays an important role in the early stages of atherosclerosis. However, the association of BS syndrome with VED, as determined using FMD, has not been reported. This study investigated the association between BS syndrome and VED using FMD. Forty-one patients with normal glucose tolerance or impaired glucose tolerance (IGT) and without macrovascular complications were evaluated using FMD from May 2017 to August 2017. Based on the BS score, the patients were divided into the non-BS (n = 19) and BS syndrome (n = 22) groups. Physical and background characteristics, physiological function test results, and laboratory data were compared. Univariate analysis revealed that FMD and a history of dyslipidemia/IGT were significantly different between the two groups (p < 0.05). Multiple logistic regression analysis showed that BS syndrome was significantly associated with FMD (odds ratio: 6.26; p=0.03) after adjusting for the history of dyslipidemia/IGT. The receiver operating characteristic curve showed that the area under the curve for BS syndrome (0.74; p < 0.001) and history of IGT (p < 0.007) provided good diagnostic accuracy for FMD. The area under the curve for “BS syndrome + IGT” showed very good accuracy (0.80; p < 0.0001) and was higher than that for BS syndrome or IGT alone. In conclusion, the results of this study suggest that the BS score in Kampo medicine could be a useful tool for detecting the early pathogenic stages of atherosclerosis.

Interleukin-17-Producing CD4+ T Cells Promote Inflammatory Response and Foster Disease Progression in Hyperlipidemic Patients and Atherosclerotic Mice.

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE−/− mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE−/− mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.

Bifurcation for a free boundary problem modeling a small arterial plaque

Atherosclerosis, hardening of the arteries, originates from small plaques in the arteries; it is a major cause of disability and premature death in the United States and worldwide. In this paper, we study the bifurcation of a highly nonlinear and highly coupled PDE model describing the growth of an arterial plaque in the early stage of atherosclerosis. The model involves LDL and HDL cholesterols, macrophage cells, and foam cells, with the interface separating the plaque and blood flow regions being a free boundary. We establish finite branches of symmetry-breaking stationary solutions which bifurcate from the radially symmetric solution. Since plaques in reality are unlikely to be strictly radially symmetric, our result would be useful to explain the asymmetric shapes of plaques.

Study on estimation of surface roughness by separation of reflection and backscattering components using ultrasonic synthetic aperture imaging

The luminal surface of the arterial wall roughens in the early-stage atherosclerosis. A possible differentiation between the reflected and scattered components in the ultrasonic echo from the arterial wall potentially can serve as a diagnostic tool when such roughening occurs. This study presents a method for the differentiation of reflection and scattering components by creating ultrasonic beams from different directions using the synthetic aperture method. The technique was evaluated in experiments on urethane rubber phantoms. The average magnitude of the echo signals from each phantom and the ratio of the mean values of the reflection and scattering components were found to be proportional to the arithmetic average roughness evaluated with a laser surface profilometer. These results show that the proposed separation technique has potentials in evaluation of surface roughness.

Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors.

There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. In total, 128 subjects (mean age 48±14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 - 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 - 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 - 0.23, p < 0.01), and LPA ( = -0.10, 95% CI -0.19 to -0.02, p=0.02) were independent associations of aSUVmax. Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects' risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. • Sodium fluoride ([18F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [18F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

Detection of Early Vascular Atherosclerosis in Type 2 Diabetes Mellitus Using Ultrasound Radiofrequency-Data Technique

ObjectivesTo quantitatively evaluate changes in vascular elasticity and intima-media thickness (IMT) of the common carotid artery (CCA) with Ultrasound radiofrequency (RF)-data technology in asymptomatic patients with type-2 diabetes mellitus (T2DM) and controls. Materials and methodsThirty-seven T2DM patients and 39 controls were enrolled. Arterial elasticity and CCA-IMT were quantitatively assessed by RF-data technology. The CCA diameters in the diastolic and systolic phases, carotid distensibility (CD), IMT, values of stiffness (β) and local pulse wave velocity (PWVβ) were measured and compared between the two groups. ResultsThe T2DM group had significantly larger CCA diastolic and systolic diameter, lower CD values, higher IMT measurements (all p < 0.001), and higher values of β and PWVβ (all P < 0.05) than the controls. Significant differences were not revealed in the mean values of IMT, β, PWVβ and CD across both sides of the CCA (all P > 0.05). ConclusionsHigher IMT measurement and lower arterial elasticity of the CCA are significantly pronounced in asymptomatic T2DM patients and may suggest atherosclerotic changes, and the ultrasound RF-data technique may be used as a potential approach for detection of early-stage atherosclerosis.

Role of myeloid-derived chemokine CCL5/RANTES at an early stage of atherosclerosis

One of the hallmarks of atherosclerosis is ongoing accumulation of macrophages in the artery intima beginning at disease onset. Monocyte recruitment contributes to increasing macrophage abundance at early stages of atherosclerosis. Although the chemokine CCL5 (RANTES) has been studied in atherosclerosis, its role in the recruitment of monocytes to early lesions has not been elucidated. We show that expression of Ccl5 mRNA, as well as other ligands of the CCR5 receptor (Ccl3 and Ccl4), is induced in the aortic intima of Ldlr−/− mice 3 weeks after the initiation of cholesterol-rich diet (CRD)-induced hypercholesterolemia. En face immunostaining revealed that CCL5 protein expression is also upregulated at 3 weeks of CRD. Blockade of CCR5 significantly reduced monocyte recruitment to 3-week lesions, suggesting that chemokine signaling through CCR5 is critical. However, we observed that Ccl5-deficiency had no effect on early lesion formation and CCL5-blockade did not affect monocyte recruitment in Ldlr−/− mice. Immunostaining of the lesions in Ldlr−/− mice and reciprocal bone marrow transplantation (BMT) of Ccl5+/+ and Ccl5−/− mice revealed that CCL5 is expressed by both myeloid and endothelial cells. BMT experiments were carried out to determine if CCL5 produced by distinct cells has functions that may be concealed in Ccl5−/−Ldlr−/− mice. We found that hematopoietic cell-derived CCL5 regulates monocyte recruitment and the abundance of intimal macrophages in 3-week lesions of Ldlr−/− mice but plays a minor role in 6-week lesions. Our findings suggest that there is a short window in early lesion formation during which myeloid cell-derived CCL5 has a critical role in monocyte recruitment and macrophage abundance.

Erythorbyl laurate suppresses TNF-α-induced adhesion of monocytes to the vascular endothelium

Abstract Erythorbyl laurate (EL) can be produced via lipase-catalyzed esterification between erythorbic acid and lauric acid. In this study, we evaluate the anti-inflammatory effect of EL in the early stage of atherosclerosis. EL suppressed tumor necrosis factor (TNF)-α-induced monocyte adhesion to vascular endothelial cells and expression of vascular cell adhesion molecule (VCAM)-1 in human umbilical vein endothelial cells (HUVECs). Additionally, EL suppressed TNF-α-induced p65/IκB kinase (IKK)/IκB phosphorylation in HUVECs. Western blot analysis of cytosolic and nuclear cell fractions and immunofluorescence showed that EL suppressed TNF-α-induced translocation of p65 from the cytoplasm to the nucleus. EL also inhibited phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinases (JNK) 1/2 in HUVECs. EL suppressed TNF-α-induced phosphorylation of Akt, IRAK1, and TAK1 in HUVECs. Quantitative RT-PCR analysis showed that EL significantly suppressed TNF-α-induced interleukin (IL)1B, IL6, TNFA, and CCL2 mRNA expression in HUVECs. Additionally, oral administration of EL suppressed TNF-α-induced IL6 and TNFA expression in the mouse aorta. EL could represent a promising functional nutrient that can be ingested for the prevention of vascular inflammation via decreased monocyte infiltration to the vascular endothelium and suppression of inflammatory nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) signaling pathways.

Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs.

Arteriolar lesions with lipid and/or amyloid deposits are frequently detected in canine gonads by routine histopathologic examination; however, they have never been examined in detail. In the present study, a total of 139 testes/epididymides and 200 ovaries from 72 male (4 months to 14 years old) and 105 female (7 months to 16 years old) dogs were examined for arteriolar lesions. Arteriolar lesions were detected in 21 of 72 male dogs (29%) and 54 of 105 female dogs (51%). These lesions were histologically classified into 4 types: "fibromuscular hypertrophy," characterized by thickening of the tunica intima; "focal vasculitis," characterized by mononuclear cell infiltration; "vacuolar change," consisting of lipid accumulation and infiltration of foamy cells; and "hyalinosis," characterized by irregular thickening with amyloid deposits. In the lesions of vacuolar change and hyalinosis, lipid deposition and infiltration of α-SMA-positive cells and Iba-1-positive cells were also observed. Foamy cells and amyloid deposits were immunopositive for apolipoproteins and oxidized low-density lipoprotein-related proteins. These results indicate that vacuolar change is possibly an early stage of atherosclerosis, and that amyloid may deposit as a consequence of the microenvironment associated with atherogenesis. Logistic regression analysis revealed that arteriolar lesions with lipid deposits were associated with age and interstitial cell tumors in male dogs, and with age in female dogs. Aging is likely an important risk factor of arteriolar lesions with lipid deposits of the canine gonads.

Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment.

Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE−/− mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

Novel insights: Dynamic foam cells derivedfrom the macrophage in atherosclerosis.

Atherosclerosis can be regarded as a chronic disease derivedfrom the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosisbut also a key stagein the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose anew ideaabout foam cells in atherosclerosis. Rather than an isolated microenvironment,the macrophage multiple lipiduptake pathways, lipidinternalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, andforma dynamic process under multi-factor regulation. The macrophage takes on different uptake lipidstatuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages isessential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamicunder multi-factor regulation, and collate thisstudy to provide a holistic and dynamic idea ofthe foam cell.

Noninvasive Assessment of Endothelial Dysfunction in Egyptian Patients with Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease characterized by tissue inflammation. There is increased cardiovascular mortality in cases with SLE. Endothelial dysfunction is an early stage of atherosclerosis, which can be reversed early. We aimed to study noninvasive assessment of endothelial dysfunction in Egyptian patients with SLE. Three hundred individuals were recruited; 100 SLE patients with lupus nephritis (LN), 100 SLE patients free of LN as well as 100 healthy volunteers. The vascular endothelial function was evaluated through ultrasonographic assessment of brachial artery diameter to determine the flow-mediated dilation (FMD) as well as a blood endothelial marker called platelet endothelial cell adhesion molecule-1, also known as cluster of differentiation 31 (CD31), was measured. CD31 is abnormal in 93% of cases with LN and 79% in cases without nephritis. There was a significant higher level in CD31 in cases of LN compared with lupus without nephritis with P = 0.016. FMD is impaired in all cases with LN, 95% in cases without nephritis, and in 20% of the controls. There was a significant lower FMD in cases of LN compared with lupus without nephritis with P <0.001. Multiple regression analysis showed that FMD of the brachial artery (P <0.001) is an independent factor to predict LN. Endothelial dysfunction is increased in cases with SLE especially those with nephritis. CD31 and FMD can be used as noninvasive methods for early detection of endothelial dysfunction.

Vasculoprotective properties of plasma lipoproteins from brown bears (Ursus arctos)

Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. The data collected and analyzed from bears were also compared with those from healthy humans. In bears, the cholesterol ester, unesterified cholesterol, TG, and phospholipid contents of VLDL and LDL were higher in winter than in summer. The percentage lipid composition of LDL differed between bears and humans but did not change seasonally in bears. Bear LDL was larger, richer in TGs, showed prebeta electrophoretic mobility, and had 5–10 times lower binding to arterial PGs than human LDL. Finally, plasma CEC was higher in bears than in humans, especially the HDL fraction when mediated by ABCA1. These results suggest that in brown bears the absence of early atherogenesis is likely associated with a lower affinity of LDL for arterial PGs and an elevated CEC of bear plasma.