Lipoprotein Distribution Research Articles

59-OR: Lipoprotein Particle Distribution by NMR in Youth with Type 2 Diabetes (T2D) in the TODAY Study

T2D in adolescents is associated with an unfavorable lipid profile, but data on lipoprotein particle size and distribution in this population have yet to be published. The TODAY Study, a randomized treatment trial of T2D in youth, provided the opportunity to evaluate lipoprotein particle distribution and relate lipoprotein particle number and size to HbA1C, need for insulin treatment, gender, race/ethnicity, BMI, and blood pressure (BP). TODAY participants (n=348) with yearly samples available for NMR Lipoprofile assessments (baseline, 12, 24, 36 mos) were included. Baseline participant characteristics (mean±SD) were: age 13.7±2.0 yrs; BMI 34.3±7.6 kg/m2; 62.4% female; 20.7% White, 32.2% Non-Hispanic Black (NHB), 43.7% Hispanic. Analysis demonstrated increasing numbers of LDL, HDL, and VLDL particles over the three yrs (all ps<0.0001) with somewhat weaker trends for decreasing particle size (LDL p=0.0009, HDL p=0.02). HbA1c showed a strong positive correlation with LDL, VLDL, and HDL particle number (all ps<0.005). HbA1c was negatively associated with LDL (p<0.0001) and HDL size (p=0.001) but positively associated with VLDL size (p<0.0001). Need for insulin treatment did not impact these associations. Female subjects had larger HDL particle size than males at baseline (p=0.0004) and throughout (p<0.0001). NHBs had the largest LDL and HDL particle size and smallest VLDL particle size. BMI% and BP showed positive association with LDL, HDL, and VLDL particle numbers but negative association with LDL and HDL size. The preponderance of lipoprotein parameters were strongly associated with TG/HDL ratio and non-HDL-C after adjusting for baseline age, race, gender, BMI%, BP, and need for insulin treatment (p<0.0001). In conclusion, these data demonstrate an atherogenic lipoprotein phenotype in youth with T2D and strong relationships with glycemic control and other cardiac risk factors. Concern regarding premature development of atherosclerosis in youth with T2D is warranted. Disclosure L.E. Katz: None. J.D. Otvos: Employee; Self; LabCorp. K. Drews: None. B. Tesfaldet: None. F. Bacha: Research Support; Self; AstraZeneca, Takeda Development Center Americas, Inc. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Tolerion, Inc. Other Relationship; Self; Caladrius Biosciences, Inc. S.M. Marcovina: None. S. Mckay: None. R.S. Weinstock: Board Member; Self; JDRF. Consultant; Self; Insulogic LLC. Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Jaeb Center for Health Research, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212)

Integral characterization of normal and alopecic hair at different degeneration stages by in-situ visible and chemical imaging.

Direct exploration to differences between normal hair (NH) and alopecic hair (AH) at different degeneration stages is still lacking. To reveal compositional and structural variation of AH with reference to NH internally and externally, infrared spectroscopic imaging combined with scanning electron microscopy was applied to investigate integral changes of hair chemical profiles and surface texture structures, and infrared macro-fingerprinting analysis revealed detailed chemical compositions of NH and AH. Results showed that AH had excessive irregular laminated structures compared to NH, leading to a lower weight bearing capacity. Spatial distributions of lipids, phosphates, lipoproteins and phospholipids in hair transverse sections showed that their infrared absorptions were intensified and gradually centralized to medulla with average variable-areas increasing upto 2.3 folds (lipoproteins area changed from 13% in NH to 30% in AH)as the alopecia progressed. Extracted pixel spectra from the chemical images showed different fingerprint characteristics in 1075-1120cm-1. Specifically, compared to NH, AH showed red shift of phosphate peaks, indicating the occurrence of phosphates transformation. In this study, in-situ visible and infrared chemical imaging directly revealed more irregular laminated scalps with decreasing weight bearing capacity and increasing distributive areas expanding to medulla of key components (phosphates, phospholipids, etc.) that were relevant to alopecia development from NH to AH, and offered a fast, eco-friendly and effective method for hair research.

Organ-specific lymphatics play distinct roles in regulating HDL trafficking and composition.

Recently, peripheral lymphatic vessels were found to transport high-density lipoprotein (HDL) from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is thought to be critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely understood. This study aimed to 1) determine the contribution of the lymphatics draining the intestine and liver (which are major sites of HDL synthesis) to total (thoracic) lymph HDL transport and 2) verify whether the HDLs in lymph are derived from specific organs and are modified during trafficking in lymph. The mesenteric, hepatic, or thoracic lymph duct was cannulated in nonfasted Sprague-Dawley rats, and lymph was collected over 5 h under anesthesia. Whole lymph and specific lymph lipoproteins (isolated by ultracentrifugation) were analyzed for protein and lipid composition. The majority of thoracic lymph fluid, protein, and lipid mass was sourced from the mesenteric, and to a lesser extent, hepatic lymph. Mesenteric and thoracic lymph were both rich in chylomicrons and very low-density lipoprotein, whereas hepatic lymph and plasma were HDL-rich. The protein and lipid mass in thoracic lymph HDL was mostly sourced from mesenteric lymph, whereas the cholesterol mass was equally sourced from mesenteric and hepatic lymph. HDLs were compositionally distinct across the lymph sources and plasma. The composition of HDL also appeared to be modified during passage from the mesenteric and hepatic to the thoracic lymph duct. Overall, this study demonstrates that the lipoproteins in lymph are organ specific in composition, and the intestine and liver appear to be the main source of HDL in the lymph.NEW & NOTEWORTHY High-density lipoprotein in lymph are organ-specific in composition and derive mostly from the intestine and liver. High-density lipoprotein also appears to be remodeled during transport through the lymphatics. These findings have implications to cardiometabolic diseases that involve perturbations in lipoprotein distribution and metabolism.

A Study of Serum Lipid Profile Changes in Children with Dengue Haemorrhagic Fever and its Correlation with Severity in a Tertiary Care Hospital

Introduction: Dengue Virus (DENV) infection now remains as the most rapidly spreading viral disease worldwide. Lower lipid level occurs in critically ill patients with DENV infection and is postulated as an independent predictor of the clinical outcome. Aim: To find the correlation between serum lipid levels and severity in children admitted with various grades of Dengue Haemorrhagic Fever (DHF) and secondarily to correlate serum lipid levels with factors like platelet count and duration of hospital stay. Materials and Methods: This was a prospective descriptive study done in the Paediatric ward from October 2019 to December 2019. Febrile Children with a platelet count of less than 1 lakh/cu.mm and positive for DENV IgM antibodies by Enzyme Linked Immuno Sorbent Assay (ELISA) formed the study group. Demographic details, number of days of fever on admission, duration of stay in hospital and severity grading of DENV infection as per the National guidelines were collected. These children were evaluated with Complete Blood Counts (CBC), fasting lipid profile, X-ray chest and ultrasound abdomen. Mean and standard deviation was used for categorical variables. Chi-square test was used to assess the strength of association between lipids and severity of DENV infections. Pearson correlation coefficient was used to assess R value between length of stay and serum lipid levels. Results: The Total Cholesterol, Low Density Lipoprotein (LDL), Triglyceride and Very Low Density Lipoprotein (VLDL) showed a simple linear decline as the severity grade advanced from grade I to grade IV. However, statistical significance was found only for total cholesterol and LDL with p-values of 0.046 and 0.041 respectively. The distribution of High Density Lipoprotein (HDL) across the grades of severity did not follow any pattern and was randomly distributed. On analysis of Pearson correlation between number of days of hospital stay and lipid profile, statistical significance was observed for LDL alone (p=0.023). Conclusion: The serum levels of total cholesterol and LDL were significantly reduced in severe grades of DHF. Serum levels of total cholesterol and LDL can be used as an economical surrogate marker to predict the severity of DHF at the time of admission.

Lipids, Lipoprotein Distribution and Nutritional Parameters over the Ramadan Period in Hemodialysis Patients.

The period of Ramadan (R) is associated with dramatic changes in eating habits involving extended periods of fasting on a daily basis. The current study assessed whether lipids and lipoproteins were impacted during R in chronic hemodialysis (HD) patients. Forty-five subjects in an outpatient dialysis clinic in Saudi Arabia were evaluated for anthropometric and lipid changes on a monthly basis before, during as well as one and two months after R. In addition to routine biochemical measures, anthropometric assessments including hand-grip strength (HGS), mid-arm muscle circumference (MAMC), plasma lipids and lipoproteins were evaluated. Dietary assessment was carried out using 24 h recalls. Over the course of the study, changes in renal-related parameters (creatinine, albumin, Kt/V) were minor, as were changes in plasma lipids. Large high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) accounted for the majority of their respective lipoproteins and their proportions did not change over the study period. Mean LDL particle diameters were higher during the R period, but the changes over the study period were small. Calorie intake during R (2139 ± 709 kcal/d) was significantly higher than the value noted two month post-R (1755 ± 424 kcal/d) and this was associated with significant increases in protein (69 ± 24 vs. 60 ± 24 g/d) and fat (97 ± 38, vs. 73 ± 35 g/d), respectively. No changes were noted with respect to HGS and MAMC. These data show that for HD patients, the period of R results in temporal or non-significant effects on plasma lipids, despite changes in nutrient intake.

Breast Milk Content of Vitamin A and E from Early- to Mid-Lactation Is Affected by Inadequate Dietary Intake in Brazilian Adult Women.

Our aims were to investigate vitamin A and E status during lactation and the determinants of breast milk content for the appropriate nutrition of the infant in a study with nursing Brazilian women. We hypothesized that both inadequate intake and the lipoprotein distribution of vitamin A and E during lactation could have an impact on their breast milk levels from early- to mid-lactation. Nineteen adult lactating women participated in this longitudinal observational study, in which dietary records, blood and mature breast milk samples were collected for the analysis of vitamin A and E, and carotenoids in early- (2nd to 4th week) and mid-lactation (12th to 14th week). Nutrient intake was balanced by the Multiple Source Method (MSM), and the intake of vitamin A and E was inadequate in 74 and 100% of the women, respectively. However, these results were not reflected in low serum concentrations of retinol and only 37% of the volunteers were vitamin E deficient according to the blood biomarker. As lactation progressed, vitamin A and E status worsened, and this was clearly observed by the decrease in their content in breast milk. The reduced content of vitamin A and E in the breast milk was not related to their distribution in lipoproteins. Taken together, the contents of vitamin A and E in breast milk seemed to be more sensitive markers of maternal nutrition status than respective blood concentrations, and dietary assessment by the MSM in early lactation was sensitive to indicate later risks of deficiency and should support maternal dietary guidance to improve the infant’s nutrition.

Short-Term Cooling Increases Plasma ANGPTL3 and ANGPTL8 in Young Healthy Lean Men but Not in Middle-Aged Men with Overweight and Prediabetes.

Angiopoietin-like proteins (ANGPTLs) regulate triglyceride (TG)-rich lipoprotein distribution via inhibiting TG hydrolysis by lipoprotein lipase in metabolic tissues. Brown adipose tissue combusts TG-derived fatty acids to enhance thermogenesis during cold exposure. It has been shown that cold exposure regulates ANGPTL4, but its effects on ANGPTL3 and ANGPTL8 in humans have not been elucidated. We therefore investigated the effect of short-term cooling on plasma ANGPTL3 and ANGPTL8, besides ANGPTL4. Twenty-four young, healthy, lean men and 20 middle-aged men with overweight and prediabetes were subjected to 2 h of mild cooling just above their individual shivering threshold. Before and after short-term cooling, plasma ANGPTL3, ANGPTL4, and ANGPTL8 were determined by ELISA. In young, healthy, lean men, short-term cooling increased plasma ANGPTL3 (+16%, p < 0.05), ANGPTL4 (+15%, p < 0.05), and ANGPTL8 levels (+28%, p < 0.001). In middle-aged men with overweight and prediabetes, short-term cooling only significantly increased plasma ANGPTL4 levels (+15%, p < 0.05), but not ANGPTL3 (230 ± 9 vs. 251 ± 13 ng/mL, p = 0.051) or ANGPTL8 (2.2 ± 0.5 vs. 2.3 ± 0.5 μg/mL, p = 0.46). We show that short-term cooling increases plasma ANGPTL4 levels in men, regardless of age and metabolic status, but only overtly increases ANGPTL3 and ANGPTL8 levels in young, healthy, lean men.

Distribution Of Elevated Lipoprotein(A) In Patients Presenting With Clinical Coronary Artery Disease

Background and Aims: To assess the range of serum lipoprotein(a) [Lp(a)] levels in an Australian population of clinical coronary artery disease (CAD) patients.

Distribution of lipoprotein (A) in a population attending a specialist care services area

Distribution of lipoprotein (A) in a population attending a specialist care services area

LPA receptor 4 deficiency attenuates experimental atherosclerosis

The widely expressed lysophosphatidic acid (LPA) selective receptor 4 (LPAR4) contributes to vascular development in mice and zebrafish. LPAR4 regulates endothelial permeability, lymphocyte migration, and hematopoiesis, which could contribute to atherosclerosis. We investigated the role of LPAR4 in experimental atherosclerosis elicited by adeno-associated virus expressing PCSK9 to lower LDL receptor levels. After 20 weeks on a Western diet, cholesterol levels and lipoprotein distribution were similar in WT male and Lpar4Y/- mice (P = 0.94). The atherosclerotic lesion area in the proximal aorta and arch was ∼25% smaller in Lpar4Y/- mice (P = 0.009), and less atherosclerosis was detected in Lpar4Y/- mice at any given plasma cholesterol. Neutral lipid accumulation in aortic root sections occupied ∼40% less area in Lpar4Y/- mice (P = 0.001), and CD68 expression was ∼25% lower (P = 0.045). No difference in α-smooth muscle actin staining was observed. Bone marrow-derived macrophages isolated from Lpar4Y/- mice displayed significantly increased upregulation of the M2 marker Arg1 in response to LPA compared with WT cells. In aortic root sections from Lpar4Y/- mice, heightened M2 "repair" macrophage marker expression was detected by CD206 staining (P = 0.03). These results suggest that LPAR4 may regulate the recruitment of specific sets of macrophages or their phenotypic switching in a manner that could influence the development of atherosclerosis.

3280 Mycobacterium bovis Bacille-Calmette-Guérin infection aggravates atherosclerosis

OBJECTIVES/SPECIFIC AIMS: The study aimed at assessing whether M. bovis BCG infection and inflammation exacerbates the development of atherosclerosis in Ldlr-/- mice. METHODS/STUDY POPULATION: Twelve-week old male Ldlr-/- mice (n=10) were infected with M. bovis BCG (0.3–3.0x10^6 colony-forming units (CFUs)) via the intranasal route, to simulate a natural respiratory route of infection. Mice were subsequently fed a western-type diet (WD) containing 21% fat and 0.2% cholesterol for 16 weeks. Age-matched uninfected Ldlr-/- mice (n=10) fed with an identical WD served as controls. Mice were euthanized after 16 weeks of WD to examine atherosclerotic lesions in aortic root sections and en face aorta using Oil Red O staining. Plasma cholesterol and triglyceride levels were measured by enzymatic assays and lipoprotein distribution was assessed using fast protein liquid chromatography. Because of the important role of T cells and monocytes in atherosclerosis development, we assessed these cell subsets in blood using flow cytometry at 8 and 16 weeks. Experiments were conducted in duplicate. We used unpaired Student’s t-test for group comparisons of numeric variables and flow cytometry data. RESULTS/ANTICIPATED RESULTS: M. bovis BCG infection significantly increased atherosclerotic lesions in en face aorta (plaque size per aorta area ratio; 0.15±0.13 vs. 0.06±0.02; P&lt;0.01), but not in the aortic root. There were no significant differences in plasma cholesterol (1,160 mg/dL vs. 1,278 mg/dL; P = 0.36), triglycerides (340 mg/dL vs. 413 mg/dL; P = 0.28), or lipoprotein profiles between infected vs. uninfected mice at 16 weeks. M. bovis BCG increased circulating T lymphocytes (1,490 cells/uL vs. 1,227 cells/uL; P = 0.03) and monocytes (901 cells/uL vs. 414 cells/uL; P&lt;0.01) within 8 weeks post-infection. When we assessed T lymphocyte subsets, M. bovis BCG infection increased total CD4+ T cell counts (556 cells/uL vs. 416 cells/uL; P&lt;0.01) but not CD8+ T cells. No differences in the proportion of CD44+CD25+ activated T lymphocytes were noted between groups. When we assessed monocyte subsets, M. bovis BCG infection increased the numbers of Ly6Chigh (709 cells/uL vs. 362 cells/uL; P&lt;0.01) and Ly6Clow (145 cells/uL vs. 35 cells/uL; P&lt;0.01) monocytes. Infection was associated with an increased proportion of Ly6Clow monocytes at week 8 (17% vs. 8%; P&lt;0.01) and week 16 (19% vs. 5%; P&lt;0.01), compared to uninfected mice. DISCUSSION/SIGNIFICANCE OF IMPACT: M. bovis BCG infection increased the extent of atherosclerosis formation in the aortas of WD-fed hyperlipidemic Ldlr-/- mice after 16 weeks. Lipid profiles were similar between infected and uninfected mice, and therefore do not explain the observed differences in atherosclerosis. Compared to uninfected controls, M. bovis BCG-infected mice exhibited increased CD4+ T cell and monocyte driven inflammation. Interestingly, M. bovis BCG-infected mice had a higher proportion of non-classical Ly6Clow monocytes, suggesting a pro-atherogenic contribution of these cells in our model. Overall, our results support a pathogenic role of mycobacterial infection in atherosclerosis development and ASCVD.

Distribution of lipoprotein (a) in a population with cardiovascular events or dyslipidaemia

Distribution of lipoprotein (a) in a population with cardiovascular events or dyslipidaemia

Subfractional distribution of APO B-containing lipoproteins in men with coronary atherosclerosis at normolipidemia

Aim: Plasma apo B-containing lipoproteins of low densities represent a heterogeneous population of particles varying by physicochemical composition, functional activity, and atherogenicity. This study was undertaken to reveal what subfractions of apo B-containing lipoproteins increase cardiovascular risk even in low LDL-cholesterol, and to find out some peculiarities in low density lipoproteins subfractional distribution in men with coronary atherosclerosis at normolipidemia.

Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders

Proprotein convertase subtilisin/kexin 9 (PCSK9), a protein regulating the number of cell-surface LDL receptors (LDLR), circulates partially associated to plasma lipoproteins. How this interaction alters PCSK9 plasma levels is still unclear. In the present study, we took advantage of the availability of a large cohort of carriers of genetic HDL disorders to evaluate how HDL defects affect plasma PCSK9 levels and its distribution among lipoproteins. Plasma PCSK9 concentrations were determined by ELISA in carriers of mutations in LCAT, ABCA1, or APOAI genes, and lipoprotein distribution was analyzed by FPLC. Carriers of one or two mutations in the LCAT gene show plasma PCSK9 levels comparable to that of unaffected family controls (homozygotes, 159.4 ng/mL (124.9;243.3); heterozygotes, 180.3 ng/mL (127.6;251.5) and controls, 190.4 ng/mL (146.7;264.4); P for trend = 0.33). Measurement of PCSK9 in plasma of subjects carrying mutations in ABCA1 or APOAI genes confirmed normal values. When fractionated by FPLC, PCSK9 peaked in a region between LDL and HDL in control subjects. In carriers of all HDL defects, lipoprotein profile shows a strong reduction of HDL, but the distribution of PCSK9 was superimposable to that of controls. In conclusion, the present study demonstrates that in genetically determined low HDL states plasma PCSK9 concentrations and lipoprotein distribution are preserved, thus suggesting that HDL may not be involved in PCSK9 transport in plasma.

Degree of Dietary Refinement Alters Apparent Gut Permeability

Previous studies in our lab showed less refined diets reduced gut permeability (GI‐p) as assessed by 4hr plasma FITC‐dextran (FITC‐d) concentration in conjunction with reduced adiposity. To determine if degree of dietary refinement altered gut health and lipoprotein biology, we conducted a 14 week feeding trial in which weanling C57Bl/6 mice (n=15/diet) were fed one of four diets differing in dietary protein source (soy or milk protein) and degree of refinement. All diets provided 20%EN PRO, 30% EN fat, and 50% EN CHO. Purified diets contained either isolated soy protein (ISP) or dried whole milk powder (DWMP) as the protein source, while non‐purified diets contained either soybean meal (SPC), or dried whole milk powder (DMC) as protein sources. Purified diets contained 14% neutral detergent fiber (NDF) as cellulose, while non‐purified soy and milk protein diets provided 11.4% and 8.4% NDF, respectively, from wheat middlings, corn, corn gluten meal and soybean meal (SPC diet). All diets provided an average 3.3 %N as analyzed by Rapid N‐cube (Elementar, Germany). Mice fed purified diets were heavier than those fed non‐purified diets, with ISP‐fed mice being heaviest (p&lt;0.033). Mice consumed similar amounts of energy in the different diets. Fecal %N was significantly increased in the non‐purified SPC‐ and DMC‐fed mice (2.99%, 2.98% respectively), being almost double that of ISP or DWMP (1.52%, 1.76%; p&lt;0.000). At week 12, apparent GI‐p was highest in ISP‐fed mice (12.8 ng/mL), being significantly increased over DMC (8.96 ng/mL; p&lt;0.02). Purified diet feeding resulted in increased apparent GI‐p, regardless of protein source (12.1 ng/mL vs. 9.56 ng/mL; p&lt;0.004). Whole‐gut transit time averaged 2.5 hours longer for mice fed purified diets (6.6 hrs vs. 4.1 hrs, p&lt;0.0001). Division of the value of 4 h FITC concentration used as the GI‐p index, by gut transit time, abolished differences due to diet purification; raising the possibility, that gut permeability per se did not differ among dietary groups. Consistent with this, cytokines (TNF‐a, IL‐1b, IL‐6, IL‐10) measured in whole blood and intestine explants were generally low and non‐indicative of either tissue or systemic inflammation. Density distributions of NBD‐stained lipoproteins showed that diets containing milk protein increased lipoproteins of d &lt; 1.019 g/mL (TRL) (3.44% v. 5.4%) and HDL (d = 1.063 – 1.18 g/mL) (64.2% v. 60.6%) and decreased LDL (d=1.019–1.063 g/mL) (30.5% v. 36.0%, p&lt;0.04). Compared to all other diets, mice fed ISP had a 30% increase in small dense LDL (d=1.05 – 1.063 g/mL) (p&lt;0.000) and a ~ 4.0% decrease in HDL‐2b (d = 1.063–1.091 g/mL) (p&lt;0.000). Increasing FITC‐d concentrations in plasma were significantly associated with decreases in %TRL (p&lt;0.0127). In diets providing macronutrient distributions following the USDA's Dietary Guidelines for Americans, degree of purification seemingly has a greater effect on GI‐P, motility, and nitrogen utilization than protein source, while milk protein‐containing diets resulted in improved lipoprotein profiles regardless of purification.Support or Funding InformationThis project was supported in part by Texas AgriLife Research [Project 8738, R.L.W.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Inside Cover: Noninvasive, high‐speed, near‐infrared imaging of the biomolecular distribution and molecular mechanism of embryonic development in fertilized fish eggs (J. Biophotonics 4/2018)

The biomaterial distribution and its molecular mechanism of embryonic development in Japanese medaka fish were visualized without staining using high‐speed near‐infrared imaging. It was a remarkable achievement to visualize the structures of eyes, lipid bilayer membranes, micelles, and water structural variations at the interface of different substances. Furthermore, insights on lipid metabolism and membrane functions were obtained from the biased distribution of lipoproteins and the presence of unsaturated fatty acids in the egg membrane.Further details can be found in the article by Mika Ishigaki (e201700115) image

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (Ldlr-/-) mice (8-12 weeks old) that were Par2+/+ or Par2-/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2- and Cxcl1-induced monocyte infiltration.

Noninvasive, high-speed, near-infrared imaging of the biomolecular distribution and molecular mechanism of embryonic development in fertilized fish eggs.

In this study, the distribution of biomaterials and its molecular mechanism of embryonic development in Japanese medaka fish were analyzed nondestructively and noninvasively without staining using near-infrared (NIR) imaging. The microscopic NIR imaging system used in this research was a device capable of ultra-high-speed imaging; using this system, one can acquire microscopic imaging data in a few seconds. Therefore, the medaka eggs remained alive throughout measurements and were successfully monitored in vivo. The distributions of biomolecules were examined by mapping the intensities of NIR bands resulting from lipids, proteins and water in 2 dimensions (2D). The structures of eyes, lipid bilayer membranes, micelles and water-structure differences at the interface of different substances constituting different structures on the egg were visualized. Furthermore, insights on the metabolic mechanisms of lipids and membrane functions were drawn from the biased distribution of lipoproteins and the presence of unsaturated fatty acids in the egg membrane. These results indicated the potential for NIR imaging in evaluating the biological functions and metabolic systems of cells and embryos.

Simulation of Low Density Lipoprotein (LDL) permeation into multilayer coronary arterial wall: Interactive effects of wall shear stress and fluid-structure interaction in hypertension

Due to increased atherosclerosis-caused mortality, identification of its genesis and development is of great importance. Although, key factors of the origin of the disease is still unknown, it is widely believed that cholesterol particle penetration and accumulation in arterial wall is mainly responsible for further wall thickening and decreased rate of blood flow during a gradual progression. To date, various effective components are recognized whose simultaneous consideration would lead to a more accurate approximation of Low Density Lipoprotein (LDL) distribution within the wall. In this research, a multilayer Fluid-Structure Interaction (FSI) model is studied to simulate the penetration of LDL into the arterial wall. Distention impact on wall properties is taken into account by considering FSI and Wall Shear Stress (WSS) dependent endothelium properties. The results show intensified permeation of LDL whilst the FSI approach is applied. In addition, luminal distension prompted by FSI reduces WSS along lumen/wall interface, especially in hypertension. This effect leads to a lowered endothelial resistance against LDL permeation, comparing to the case in which WSS effect is overlooked. The results are in an acceptable consistency with the clinical researches on WSS effect on atherosclerosis development.

Preoperative Cardiac Risk Assessment in Renal Transplant Recipients: A Single-Center Experience.

Cardiovascular disease is the major cause of morbidity and mortality in patients on renal replacement therapy and in kidney transplant recipients. There are no specific recommendations for preoperative cardiac risk assessment before renal transplant. The aim of our study was to analyze preoperative cardiac test frequencies, test results, patient characteristics, and relations between cardiac stress test results and severe coronary artery disease. We retrospectively examined patients who underwent renal transplant between December 2011 and December 2016 in our hospital (Ankara, Turkey). Our study group included 216 patients. All patients had preoperative echocardiography. We recorded results of exercise stress tests, myocardial perfusion scintigraphy, and coronary angiography. For all patients, preoperative complete blood cell count, creatinine, high-density lipoprotein, triglycerides, low-density lipoprotein, and red cell distribution width values were obtained and recorded. We classified patient groups according to presence or absence of severe coronary artery disease. Fourteen of 66 patients had severe coronary artery disease. In univariate analyses, age, having a history of familial coronary artery disease, diabetes mellitus, presence of coronary artery disease, and triglyceride levels were risk factors for severe coronary artery disease. In multivariate analysis, diabetes mellitus, presence of coronary artery disease, and having a history of familial coronary artery disease were statistically significant. Renal transplant recipients are a special patient population, and there must be specific suggestions for this population. If patients present with more than 1 risk factor, a stress test should be performed to evaluate cardiovascular risk. In some patients, especially those whose risk factors include prior cardiovascular disease or diabetes mellitus, stress tests should be skipped and patients should directly undergo coronary angiography to look for severe coronary artery disease.