Lipoprotein Transport Research Articles

Severe Familial Hypertriglyceridemia: Successful Treatment With Insulin and a Modified Meal Plan.

ContextMutations in genes encoding the lipoprotein lipase enzyme, its cofactor, or transport proteins can cause severe familial hypertriglyceridemia, resulting in serious complications, such as severe pancreatitis, hepatosplenomegaly, lipid encephalopathy, and failure to thrive. Current treatment includes a low-saturated-fat formula enriched with high medium-chain triglyceride (TGs), oral fibrates, omega-3 fatty acids, or plasmapheresis.Case DescriptionA 71-day-old infant with very severe hypertriglyceridemia and recurrent pancreatitis associated with a likely pathogenic variant in the LPL gene was treated successfully with insulin infusion and a locally prepared low-fat formula feed after stopping breast milk. Subcutaneous insulin was administered daily from 9 to 30 months of age. His serum TG level was markedly lower, although higher than normal. No episodes of hypoglycemia were noted. Fenofibrate and omega-3 fatty acids were ineffective in this infant. At the last follow-up visit, he was 36 months old and growing normally. He was consuming a special meal plan and receiving insulin injections during high-fat meals. Two other young infants with severe hypertriglyceridemia were growing normally after a short course of insulin infusion and the same modified reduced long chain fat diet.ConclusionsInsulin is an unusual and affordable therapeutic option for some patients with severe hypertriglyceridemia and can be helpful in the prevention of acute and chronic complications. Locally available cereals and millets with high crude fiber and a low glycemic index, along with medium chain TGs, was used to prepare an economical special formula at home to maintain TG concentrations in the acceptable limits.

Genetic factors involved in the bioavailability of tomato carotenoids.

To provide an update on the genetic factors recently associated with the interindividual variability of tomato carotenoid bioavailability. Several clinical studies have demonstrated that the main carotenoids found in tomatoes (lycopene, phytoene, phytofluene, β-carotene, lutein) all display relatively large interindividual variabilities of their bioavailability, with coefficients of variations more than 70%. The bioavailability of the parent molecules, and the blood/tissue appearance of their metabolites, is modulated by numerous proteins, involved in intestinal absorption and metabolism, blood lipoprotein transport or tissue uptake. Several single nucleotide polymorphisms (SNPs) have been associated with the interindividual variability of lycopene, lutein and β-carotene bioavailability, with six genes consistently shared between the three carotenoids, and in particular one SNP in ELOVL fatty acid elongase 2. The effects of the genetic variants taken separately are relatively low, that is each variant is usually associated with only a few percentage of the variability but multivariate analyses suggest that the additive effect of several genetic variants can explain a significant fraction of tomato carotenoid bioavailability. Additional studies are needed to improve our knowledge of the genetic determinants of tomato carotenoid bioavailability but progress in this field could one day allow nutritionists to provide more personalized dietary recommendations.

Endothelial Transcytosis of Lipoproteins in Atherosclerosis.

Seminal studies from Nikolai Anichckov identified the accumulation of cholesterol in the arteries as the initial event that lead to the formation of atherosclerotic plaques. Further studies by Gofman and colleagues demonstrated that high levels of circulating low-density lipoprotein cholesterol (LDL-C) was responsible for the accelerated atherosclerosis observed in humans. These findings were confirmed by numerous epidemiological studies which identified elevated LDL-C levels as a major risk factor for cardiovascular disease. LDL infiltrates in the arterial wall and interacts with the proteoglycan matrix promoting the retention and modification of LDL to a toxic form, which results in endothelial cell (EC) activation and vascular inflammation. Despite the relevance of LDL transport across the endothelium during atherogenesis, the molecular mechanism that control this process is still not fully understood. A number of studies have recently demonstrated that low density lipoprotein (LDL) transcytosis across the endothelium is dependent on the function of caveolae, scavenger receptor B1 (SR-B1), activin receptor-like kinase 1 (ALK1), and LDL receptor (LDLR), whereas high-density lipoproteins (HDL) and its major protein component apolipoprotein AI transcytose ECs through SR-B1, ATP-Binding cassette transporter A1 (ABCA1) and ABCG1. In this review article, we briefly summarize the function of the EC barrier in regulating lipoprotein transport, and its relevance during the progression of atherosclerosis. A better understanding of the mechanisms that mediate lipoprotein transcytosis across ECs will help to develop therapies targeting the early events of atherosclerosis and thus exert potential benefits for treating atherosclerotic vascular disease.

Emerging Roles of Vascular Endothelium in Metabolic Homeostasis.

Our understanding of the role of the vascular endothelium has evolved over the past 2 decades, with the recognition that it is a dynamically regulated organ and that it plays a nodal role in a variety of physiological and pathological processes. Endothelial cells (ECs) are not only a barrier between the circulation and peripheral tissues, but also actively regulate vascular tone, blood flow, and platelet function. Dysregulation of ECs contributes to pathological conditions such as vascular inflammation, atherosclerosis, hypertension, cardiomyopathy, retinopathy, neuropathy, and cancer. The close anatomic relationship between vascular endothelium and highly vascularized metabolic organs/tissues suggests that the crosstalk between ECs and these organs is vital for both vascular and metabolic homeostasis. Numerous reports support that hyperlipidemia, hyperglycemia, and other metabolic stresses result in endothelial dysfunction and vascular complications. However, how ECs may regulate metabolic homeostasis remains poorly understood. Emerging data suggest that the vascular endothelium plays an unexpected role in the regulation of metabolic homeostasis and that endothelial dysregulation directly contributes to the development of metabolic disorders. Here, we review recent studies about the pivotal role of ECs in glucose and lipid homeostasis. In particular, we introduce the concept that the endothelium adjusts its barrier function to control the transendothelial transport of fatty acids, lipoproteins, LPLs (lipoprotein lipases), glucose, and insulin. In addition, we summarize reports that ECs communicate with metabolic cells through EC-secreted factors and we discuss how endothelial dysregulation contributes directly to the development of obesity, insulin resistance, dyslipidemia, diabetes mellitus, cognitive defects, and fatty liver disease.

Hyperlipidemia modifies HDL-mirna profile and enhances endothelial delivery of HDL- MIR126-3P/-5P through a SRB-1-dependent mechanism

Aim: High-density lipoproteins (HDLs) transport endogenous miRNAs and deliver them to recipient cells with functional targeting capabilities. The impact of high-cholesterol levels on HDL-miRNA signature remains unknown. We investigated the effect of hypercholesterolemia on HDL-miRNA profile and miRNA delivery to endothelial cells.

Differerential and antagonistic regulation of transendothelial transport of HDL and LDL by sphingosine-1-phosphate receptors 1 and 3

Aim: Sphingosine-1-phosphate (S1P) preserves the endothelial barrier and is transported by both HDL and LDL. This raises the question, how S1P and its cognate receptors S1P1 and S1P3 regulate the transendothelial transport of lipoproteins.

Reticulon 3 regulates very low density lipoprotein secretion by controlling very low density lipoprotein transport vesicle biogenesis.

Secretion of very low density lipoprotein (VLDL) by the liver is an important physiological process; however, the rate of VLDL secretion is determined by its transport from the endoplasmic reticulum (ER) to the Golgi. This transport event is facilitated by a specialized ER-derived vesicle, the VLDL transport vesicle (VTV). We have reported earlier a detailed VTV proteome, which revealed that reticulon 3 (RTN3) is uniquely present in the VTV. Our immunoblotting and electron microscopic data demonstrate that RTN3 is enriched in the VTV; however, other ER-derived vesicles do not contain RTN3. Co-immunoprecipitation data coupled with confocal microscopic analyses strongly suggest that RTN3 interacts with VLDL core protein, apoB100, at the ER level. Our data show that either blocking of RTN3 using specific antibodies or RTN3 knockdown resulted in significant reduction in VTV biogenesis from hepatic ER membranes. Additionally, VLDL secretion from hepatocytes was significantly decreased when RTN3 was silenced by RTN3 siRNA. We conclude that RTN3 regulates VLDL secretion by controlling VTV-mediated ER-to-Golgi transport of nascent VLDL.

Abstract 576: LDL-Trafficked Small RNAs Promote Atherosclerosis through TLR Signaling in Macrophages

Atherosclerosis is a chronic inflammatory disease, and despite resounding success in lipid management to reduce cardiovascular events, most heart attacks in the US occur in patients with clinically normal LDL-C levels. The next generation of therapies for cardiovascular disease (CVD) will include inflammation-based targets; however, systemic immune suppression has limitations. Thus, the critical barrier for successful targeting of inflammation in CVD is the identification of vascular ligands that drive immune cell activation. Previously, we demonstrated that low-density lipoproteins (LDL) transport microRNAs. Here, we report that LDL traffic a wide-diversity of small non-coding RNAs (sRNA) in circulation, many of which are derived from exogenous species, e.g. bacteria and fungi. Moreover, using high-throughput sRNA sequencing, we found that LDL-sRNA signatures are influenced primarily by environmental microbiota, as opposed to commensal bacteria in the gut microbiome. Using a mouse model of compromised mucosal immunity, we identified a process by which LDL accumulates bacterial sRNAs. Next, we demonstrated that native LDL potently stimulated cytokine release from macrophages through activation of single-stranded RNA (ssRNA)-sensing toll-like receptor (TLR) signaling, which was blunted by partial silencing of ssRNA-sensing TLRs in macrophages. Most importantly, preliminary results in mice suggest that targeting ssRNA-sensing TLRs is a potential strategy to suppress atherosclerosis. Taken together, we put forth a novel paradigm in which, LDL scavenge microbial sRNAs to promote clearance during health, yet serve as TLR-ligands that propagate macrophage inflammation in hypercholesterolemia, which likely contributes to the underlying inflammation in the pathogenesis of CVD.

Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins

We aim to examine if circulating micro-RNA and cytokine levels associate with dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines were quantified using microfluidic RT-qPCR and multiplex solid-phase immunoassays, respectively. Micro-RNA and cytokine profiling were examined for associations with dementia diagnoses in a longitudinal registry study or with cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were detected consistently. Micro-RNA profiles associate with diagnoses and cognitive scores at statistically significant levels while cytokine only showed trends pointing at chronic inflammation in twins having or developing dementia. The most notable findings were decreased miR-106a and miR-210, and increased miR-106b expression in twins with a dementia diagnosis. This pioneering evaluation of micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

Hepatic Overexpression of Endothelial Lipase Lowers High-Density Lipoprotein but Maintains Reverse Cholesterol Transport in Mice: Role of Scavenger Receptor Class B Type I/ATP-Binding Cassette Transporter A1-Dependent Pathways.

Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways.

Gene-gene interactions among coding genes of iron-homeostasis proteins and APOE-alleles in cognitive impairment diseases

Cognitive impairments of different aetiology share alterations in iron and lipid homeostasis with mutual relationships. Since iron and cholesterol accumulation impact on neurodegenerative disease, the associated gene variants are appealing candidate targets for risk and disease progression assessment. In this light, we explored the role of common single nucleotide polymorphisms (SNPs) in the main iron homeostasis genes and in the main lipoprotein transporter gene (APOE) in a cohort of 765 patients with dementia of different origin: Alzheimer’s disease (AD) n = 276; vascular dementia (VaD), n = 255; mild cognitive impairment (MCI), n = 234; and in normal controls (n = 1086). In details, four genes of iron homeostasis (Hemochromatosis (HFE: C282Y, H63D), Ferroportin (FPN1: -8CG), Hepcidin (HAMP: -582AG), Transferrin (TF: P570S)), and the three major alleles of APOE (APOE2, APOE3, APOE4) were analyzed to explore causative interactions and synergies. In single analysis, HFE 282Y allele yielded a 3-fold risk reduction in the whole cohort of patients (P<0.0001), confirmed in AD and VaD, reaching a 5-fold risk reduction in MCI (P = 0.0019). The other iron SNPs slightly associated with risk reduction whereas APOE4 allele resulted in increased risk, reaching more than 7-fold increased risk in AD homozygotes (P = 0.001), confirmed to a lower extent in VaD and MCI (P = 0.038 and P = 0.013 respectively) as well as in the whole group (P<0.0001). Comparisons of Mini Mental State Examination (MMSE) among AD showed appreciable lowering in APOE4 carriers (P = 0.038), confirmed in the whole cohort of patients (P = 0.018). In interaction analysis, the HFE 282Y allele completely extinguished the APOE4 allele associated risk. Conversely, the coexistence in patients of a substantial number of iron SNPs accrued the APOE4 detrimental effect on MMSE. Overall, the analysis highlighted how a specific iron-allele burden, defined as different combinations of iron gene variants, might have different effects on cognitive impairment and might modulate the effects of established genetic risk factors such as APOE4. Our results suggest that established genetic risk factors might be affected by specific genetic backgrounds, making patients differently suited to manage iron accumulation adding new genetic insights in neurodegeneration. The recently recognized interconnections between iron and lipids, suggest that these pathways might share more than expected. We therefore extended to additional iron gene variants the newly proposed influencing mechanisms that HFE gene has on cholesterol metabolism. Our results have a strong translational potential promoting new pharmacogenetics studies on therapeutic target identification aimed at optimally tuning brain iron levels.

Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis: Re-Examining Lipoprotein Transport Mechanisms Among Diverse Gram-Negative Bacteria While Exploring New Discoveries and Questions.

The Gram-negative outer membrane (OM) is a potent permeability barrier against antibiotics, limiting clinical options amid mounting rates of resistance. The Lol transport pathway delivers lipoproteins to the OM. All the OM assembly machines require one or more OM lipoprotein to function, making the Lol pathway central for all aspects of OM biogenesis. The Lol pathways of many medically important species clearly deviate from the Escherichia coli paradigm, perhaps with implications for efforts to develop novel antibiotics. Moreover, recent work reveals the existence of an undiscovered alternate route for bringing lipoproteins to the OM. Here, lipoprotein transport mechanisms, and the quality control systems that underpin them, is re-examined in context of their diversity.

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors.

Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa) and document their effects on the blood-brain barrier (BBB) permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

Melanocortin overexpression limits diet-induced inflammation and atherosclerosis in LDLR-/- mice.

Atherosclerosis is a chronic inflammatory disease of the arteries. The disease is initiated by endothelial dysfunction that allows the transport of leukocytes and low-density lipoprotein into the vessel wall forming atherosclerotic plaques. The melanocortin system is an endogenous peptide system that regulates, for example, energy homeostasis and cardiovascular function. Melanocortin treatment with endogenous or synthetic melanocortin peptides reduces body weight, protects the endothelium and alleviates vascular inflammation, but the long-term effects of melanocortin system activation on atheroprogression remain largely unknown. In this study, we evaluated the effects of transgenic melanocortin overexpression in a mouse model of atherosclerosis. Low-density lipoprotein receptor-deficient mice overexpressing alpha- and gamma3-MSH (MSH-OE) and their wild-type littermates were fed either a regular chow or Western-style diet for 16 weeks. During this time, their metabolic parameters were monitored. The aortae were collected for functional analysis, and the plaques in the aortic root and arch were characterised by histological and immunohistochemical stainings. The aortic expression of inflammatory mediators was determined by quantitative PCR. We found that transgenic MSH-OE improved glucose tolerance and limited atherosclerotic plaque formation particularly in Western diet-fed mice. In terms of aortic vasoreactivity, MSH-OE blunted alpha1-adrenoceptor-mediated vasoconstriction and enhanced relaxation response to acetylcholine, indicating improved endothelial function. In addition, MSH-OE markedly attenuated Western diet-induced upregulation of proinflammatory cytokines (Ccl2, Ccl5 and Il6) that contribute to the pathogenesis of atherosclerosis. These results show that the activation of the melanocortin system improves glucose homeostasis and limits diet-induced vascular inflammation and atherosclerotic plaque formation.

Brinkman-Forchheimr model for fat accumulation in arterial wall

A new model based on Brinkman-Forchheimr equation on transport of low-density lipoprotein (LDL) in artery wall has been developed that includes the multi-layered model. Artery wall has been considered as homogeneous porous media, Staverman filtration and osmotic reflection coefficient has been considered. The realistic physical properties are available and have been obtained from the literature. Various models have been compared with the proposed model. The results are consistent with the other numerical and experimental studies. Effects of hypertension and pulsatile flow on LDL transport in arterial multi-layered wall have been studied in detail. Effect of pulsatile flow is imperative since blood flow in artery is a pulsatile flow. Hyperthermia is important for the treatment of cancer. Soret effect on LDL concentration distribution has been analysed for the hyperthermia condition. This model will help to better understand the effect of hypertension and hyperthermia on atherosclerotic diseases. Results reveal that LDL accumulation is directly related to the transmural pressure. For the straight artery, effect of hyperthermia is negligible for LDL accumulation due to the very thin arterial wall. Effect of pulsatile flow in LDL transport has been found negligible.

Effect of pulsatile blood flow on LDL transport in arterial layers

Considering the pulsatile nature of blood flow, the transport of low density lipoprotein (LDL) species in the arterial wall has been numerically analysed. A straight axi-symmetric arterial segment with four arterial porous layers vis. endothelium, intima, internal elastic lamina and media has been taken into consideration. These layers are considered porous in nature. For modelling the fluid flow in the lumen and the arterial wall, Navier-Stokes equation and Darcy's equation have been used respectively. The solute flow modelling in the lumen and in the arterial wall has been done by using convection-diffusion equation and convection-diffusion-reaction equation respectively. Simple pulsatile and physiological pulsatile model of blood flow have been considered in the present analysis. The present study shows that the physiological pulsatile flow is having more impact on the radial filtration velocity at lumen-endothelium interface than that of the case for simple pulsatile nature of flow. Therefore, the possibility of enhancement in solute transport in the arterial wall is more in case of physiological pulsatile nature of flow.

The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia

Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis in mice. Here, we report that this is explained by an ∼60% reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein structure, lipid binding, and transport. The ApoE promoter contains a functional Zfp125-binding element that is also present in 17 other lipid-related genes repressed by Zfp125. While liver-specific knockdown of Zfp125 causes an "Alb-D2KO-like" metabolic phenotype, liver-specific normalization of Zfp125 expression in Alb-D2KO mice rescues the phenotype, restoring normal susceptibility to diet-induced obesity, liver steatosis, and hypercholesterolemia.

What is needed to make low-density lipoprotein transport in human aorta computational models suitable to explore links to atherosclerosis? Impact of initial and inflow boundary conditions

Personalized computational hemodynamics (CH) is a promising tool to clarify/predict the link between low density lipoproteins (LDL) transport in aorta, disturbed shear and atherogenesis. However, CH uses simplifying assumptions that represent sources of uncertainty. In particular, modelling blood-side to wall LDL transfer is challenged by the cumbersomeness of protocols needed to obtain reliable LDL concentration profile estimations. This paucity of data is limiting the establishment of rigorous CH protocols able to balance the trade-offs among the variety of in vivo data to be acquired, and the accuracy required by biological/clinical applications.In this study, we analyze the impact of LDL concentration initialization (initial conditions, ICs) and inflow boundary conditions (BCs) on CH models of LDL blood-to-wall transfer in aorta. Technically, in an image-based model of human aorta, two different inflow BCs are generated imposing subject-specific inflow 3D PC-MRI measured or idealized (flat) velocity profiles. For each simulated BC, four different ICs for LDL concentration are applied, imposing as IC the LDL distribution resulting from steady-state simulations with average conditions, or constant LDL concentration values.Based on CH results, we conclude that: (1) the imposition of realistic 3D velocity profiles as inflow BC reduces the uncertainty affecting the representation of LDL transfer; (2) different LDL concentration ICs lead to markedly different patterns of LDL transfer.Given that it is not possible to verify in vivo the proper LDL concentration initialization to be applied, we suggest to carefully set and unambiguously declare the imposed BCs and LDL concentration IC when modelling LDL transfer in aorta, in order to obtain reproducible and ultimately comparable results among different laboratories.

A multiphysics approach for modeling early atherosclerosis.

This work is devoted to the development of a mathematical model of the early stages of atherosclerosis incorporating processes of all time scales of the disease and to show their interactions. The cardiovascular mechanics is modeled by a fluid-structure interaction approach coupling a non-Newtonian fluid to a hyperelastic solid undergoing anisotropic growth and a change of its constitutive equation. Additionally, the transport of low-density lipoproteins and its penetration through the endothelium is considered by a coupled set of advection-diffusion-reaction equations. Thereby, the permeability of the endothelium is wall-shear stress modulated resulting in a locally varying accumulation of foam cells triggering a novel growth and remodeling formulation. The model is calibrated and applied to an murine-specific case study, and a qualitative validation of the computational results is performed. The model is utilized to further investigate the influence of the pulsatile blood flow and the compliance of the artery wall to the atherosclerotic process. The computational results imply that the pulsatile blood flow is crucial, whereas the compliance of the aorta has only a minor influence on atherosclerosis. Further, it is shown that the novel model is capable to produce a narrowing of the vessel lumen inducing an adaption of the endothelial permeability pattern.

Reverse cholesterol transport and other functions of high density lipoprotein are enhanced after bariatric surgery

Reverse cholesterol transport and other functions of high density lipoprotein are enhanced after bariatric surgery