Vascular Intima Research Articles

Atherosclerosis: nexus of vascular dynamics and cellular cross talks.

Cardiovascular diseases (CVDs) are the foremost cause of mortality worldwide. Atherosclerosis is the underlying pathology behind CVDs. Atherosclerosis is manifested predominantly by lipid deposition, plaque formation, and inflammation in vascular intima. Initiation and progression of plaque require many years. With aging, atherosclerotic plaques become vulnerable. Localization of these plaques in the coronary artery leads to myocardial infarction. A complete understanding of the pathophysiology of this multifaceted disease is necessary to achieve the clinical goal to provide early diagnosis and the best therapeutics. The triggering factors of atherosclerosis are biomechanical forces, hyperlipidemia, and chronic inflammatory response. The current review focuses on crucial determinants involved in the disease, such as location, hemodynamic factors, oxidation of low-density lipoproteins, and the role of endothelial cells, vascular smooth muscle cells, and immune cells, and better therapeutic targets.

Removal of Shield Needles from Graphene Oxide Thrombus and Preparation

Atherosclerosis is a chronic inflammatory disease commonly seen in clinical practice. It can lead to thickening of vascular intima, occlusion of lumen stenosis and thrombosis, leading to angina pectoris, hypertension, myocardial infarction and other diseases, posing a serious threat to human life and health. This study provides a method for removing shield needles from graphene oxide thrombus and its preparation. The graphene oxide shield needle mainly includes flexible rotating shaft, radial flexible rod, rotating needle, adsorption main pipe and dosing main pipe, laser measuring device, high definition camera and other structures, which has the following advantages:firstly, it achieves multi-angle rotation grinding thrombosis, precise rotation grinding, avoids vascular damage and infection; secondly, thrombolytic drugs can be applied in the process of rotary grinding and small thrombus can be adsorbed to effectively avoid secondary embolization of blood vessels; thirdly, it a coating of graphene oxide on a rotating needle, which protects against bacteria and infection. This study has practical reference value for the development of thrombotherapy and the application of graphene in the medical field.

Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review.

Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.

Corilagin ameliorates atherosclerosis by regulating MMP-1, -2, and -9 expression in vitro and in vivo

Corilagin is a polyphenol has been identified anti-inflammatory properties. However, the anti-atherosclerotic effects of corilagin are not well understood. Here, we evaluated the anti-atherosclerotic effects and the underlying mechanisms of corilagin. We also verified whether corilagin can reverse atherosclerosis by regulating matrix metalloproteinase (MMP)-1, -2, and -9 in vitro and in vivo. An atherosclerosis model was established by feeding minipigs a high-fat diet combined with balloon injury, and the effects of different concentrations of corilagin on common carotid artery atherosclerosis in minipigs were monitored. Murine RAW264.7 macrophages were cultured and induced with oxidized low-density lipoprotein; fluorescence microscopy revealed the nuclear translocation of NF-κB. Furthermore, MMP-1, -2, and -9 expression in common carotid artery plaques and cellular models was detected by immunohistochemistry, western blotting, and RT-PCR. The pathological results suggested that the vascular intima of the model control group was significantly thickened, a large amount of collagen fibers was deposited, endothelial cells were damaged and detached, and plaque and foam cell formation occurred to varying degrees on the arterial wall, with lipid deposition. Corilagin treatment significantly reduced the degree of injury in the common carotid artery and decreased the number of lipid plaques and foam cells. Additionally, corilagin downregulated MMP-1, -2, and -9 expression in the common carotid artery plaques and cellular model. Moreover, corilagin significantly inhibited NF-κB nuclear translocation in vitro. Overall, corilagin exerted substantial therapeutic effects on experimental atherosclerotic minipigs via the downregulation of MMP-1, -2, and -9 expression.

Factors Affecting the Re-Endothelialization of Endothelial Progenitor Cell.

The vascular endothelium, which plays an essential role in maintaining the normal shape and function of blood vessels, is a natural barrier between the circulating blood and the vascular wall tissue. The endothelial damage can cause vascular lesions, such as atherosclerosis and restenosis. After the vascular intima injury, the body starts the endothelial repair (re-endothelialization) to inhibit the neointimal hyperplasia. Endothelial progenitor cell is the precursor of endothelial cells and plays an important role in the vascular re-endothelialization. However, re-endothelialization is inevitably affected in vivo and in vitro by factors, which can be divided into two types, namely, promotion and inhibition, and act on different links of the vascular re-endothelialization. This article reviews these factors and related mechanisms.

Gout-induced endothelial impairment: The role of SREBP2 transactivation of YAP.

Gout is a multifaceted inflammatory disease involving vascular impairments induced by hyperuricemia. Experiments using human umbilical vein endothelial cells treated with uric acid (UA), monosodium urate (MSU), or serum from gout patients showed increased expression of pro-inflammatory genes (ie, VCAM1, ICAM1, CYR61, CCNA1, and E2F1) with attendant increase in monocyte adhesion. Mechanistically, UA- or MSU-induced SREBP2 expression and its transcriptional activity. RNA sequencing analysis and real-time PCR showed the induction of YAP signaling and pro-inflammatory pathways in HUVECs transfected with adenovirus-SREBP2. The SREBP2 knockdown by siRNA partially abolished UA- or MSU-induced YAP activity, pro-inflammatory gene expression, and monocytes adhesion. Vascular intima from transgenic mice overexpressing SREBP2 in endothelium or mice with hyperuricemia exhibited activated YAP signaling and increased expression of pro-inflammatory genes. Betulin, an SREBP pharmacological inhibitor, attenuated the UA-, MSU-, or gout serum-induced endothelial cell inflammation and dysfunction. In the human study, endothelial cell function, assessed by EndoPAT, was negatively correlated with serum UA level among gouty patients and healthy controls. Collectively, UA or MSU causes endothelial dysfunction via SREBP2 transactivation of YAP. Betulin inhibition of SREBP2 may restrain gout-induced endothelial dysfunction.

Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy.

Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.

EXTENSIVE ANTERIOR WALL ST ELEVATED MYOCARDIAL INFARCTION FOLLOWING STEERING WHEEL IMPACT AND BLUNT CHEST TRAUMA IN A ROAD TRAFFIC ACCIDENT: A RARE CASE REPROT

Background: Blunt trauma chest may rarely lead to acute myocardial infarction. Shear force generated from trauma causes tearing, laceration of coronary vascular intima and results in intraluminal thrombosis. Left anterior descending (LAD) artery is the most common to be involved secondary to its proximity to anterior chest wall. Case Presentation: We report a case of 38year old hypertensive male presented in emergency room with complaints of left sided chest pain &amp; diaphoresis for one hour following trauma to his chest from steering wheel following a collision between two four wheeler. During primary survey as per ATLS guideline 12 ECG revealed acute extensive anterior wall STEMI. Other associated injuries were left frontal non hemorrhagic contusion, bilateral minimal pneumothorax, multiple bilateral rib fractures, mild hemoperitoneum with small hematoma in retroperitoneum and serosal surface of stomach. Urgent coronary angiography done by cardiologist on call and patient was diagnosed with single vessel coronary artery disease involving LAD with severe systolic LV dysfunction. Percutaneous transmural coronary angioplasty (PTCA) was done by a drug eluting stent in LAD. Conclusion: An emergencyphysician should consider cardiac complications in patients with chest trauma including myocardial infarction, early diagnosis of which is critical to save the myocardium.Any delay in diagnosis can be detrimental. What we already know? There are quite a few case reports that already mentioned about possibility of acute myocardial infarction after blunt chest trauma following road traffic accident secondary to intimal laceration of coronary artery and intraluminal thrombosis. Most coomonly left anterior descending artery is involved. What this paper adds?This is rare case report of acute &amp; extensive anterior wall myocardial infarction secondary to single vessle coronary artery involvement after blunt chest trauma by steering wheel in a road traffic accident. We specifically points towards the fact that noobvious Clinical guideline to manage these kind of cases mentioned in literature.Hence proper clinical guidelines to manage such kind of cases. Also, in acute myocardial infarction post blunt trauma chest, PCI seems to be a better option than thrombolysis keeping in mind of other injuries.

Enhancement of Nanozyme Permeation by Endovascular Interventional Treatment to Prevent Vascular Restenosis via Macrophage Polarization Modulation

AbstractThe long‐term prognosis of vascular restenosis after endovascular interventional treatment is a critical challenge in a clinical setting. Over‐production of reactive oxygen species (ROS) is a major factor to aggravate vascular restenosis. Current clinical pharmacological interventions for vascular restenosis are still unsatisfactory. Based on the intrinsic ROS scavenging properties, nanozymes have been widely applied in the treatment of inflammatory‐related diseases. However, the vascular endothelial cell barrier hinder the delivery efficiency of intravenously injected nanomaterials in most diseases. Herein, an effective therapeutic strategy for vascular restenosis is developed based on endothelial cells exfoliation by endovascular interventional treatment through vascular balloon injury, which provides an opportunity to enhance nanozyme passive permeation into the vascular intima and uptake by macrophages to alleviate long‐term vascular restenosis in vivo. Moreover, the macrophages polarization modulation mechanism of vascular restenosis prevention is further investigated. This interesting discovery that endothelial cells exfoliation enhanced nanoparticle vascular permeation by endovascular interventional treatment may provide applicative perspectives in the treatment of other disease by nanomaterials.

Features of immune regulation and specific sensitization in children of the Northern Siberia

This paper highlights the features of immune regulation and specific hypersensitivity in children residing in the Northern Siberia being exposed to the extreme climatic and exogenous chemical risk factors. An immunological diagnostic examination of 255 children permanently residing in the region of exogenous hapten exposure was conducted. The control group consisted of 130 children residing on the territory not being exposed to exogenous chemical factors. Level of serum class G, A, M immunoglobulins was assessed by using a Mancini radial immunodiffusion reaction. Amount of total serum IgE, neuron-specific enolase, and VEGF was measured by using the ELISA. Changes in level of IgG specific to phenol and copper as well as IgE specific to nickel and benz(a)pyrene were measured by using enzyme-linked allergosorbent test. Peripheral blood lymphocyte subsets were analyzed by using membrane-bound immunofluorescence with a panel of labeled specific monoclonal antibodies. High-quality statistical data analysis was performed by using Microsoft® Office Excel 2003 software as well as Statistica 6.0 application software package (StatSoft, USA). Statistical significance was determined by using Student’s t-test. Relation between signs was estimated by using correlation and regression analysis as well as Fisher’s test. Immunological study demonstrated that immunogram parameters were significantly changed in the observation group by containing increased percentage of CD16+ effector cells absolute and relative CD19+ cell count (p ≤ 0.05), relative and absolute count of CD25+ lymphocytes (p ≤ 0.05) as well as CD95+T cells as compared to the reference values and control group (p ≤ 0.05). Moreover, level of neuron-specific enolase and VEGF (vascular endothelial growth factor) was increased compared to control group (p ≤ 0.05). It points that regulatory mediators potentially mapped to the glia and vascular intima in children from the observation group were extremely activated. The level of both total (total IgE) and specific sensitization was significantly increased by assessing immunoglobulin G specific to phenol as well as immunoglobulin E specific to nickel and benz(a)pyrene (p 0.05). Parameters of programmed cell death were significantly altered that was paralleled with simultaneous activation of general and specific sensitization highlighting features of the immunological status in children examined distinguished by excessive stress of immune regulatory arms in case of combined exposure to climate-geographic as well as exogenous chemical risk factors.

ROLE OF TRPV4 CHANNEL SIGNALING IN SHEAR STRESS RESPONSES

Shear stress along the vascular intima promotes blood flow and preserves vascular wall structure, providing vital protection against progressive cardiovascular disease. Indeed, obstructive cardiovascular disease states such as atherosclerosis are associated with early shear stress disruption that leads to endothelial dysfunction and vascular remodeling. A key feature of shear stress action is a rapid and sustained increase in dynamic (spatially and temporally) Ca2+ signals within the endothelium, which promotes vasodilation and opposes inflammation. Although specific mechanisms remain unclear, recent studies have implicated mechanosensitive TRPV4 cation channels in shear stress mediated Ca2+ entry. We hypothesize that shear stress‐induced endothelial Ca2+ signals arise from graded recruitment of TRPV4 Ca2+ transients. We performed Ca2+ imaging studies on arteries isolated from wild type and genetically altered TRPV4 knockout mice. Carotid arteries were isolated, opened, and mounted in specialized flow chambers. The chambers were connected to a peristaltic pump and placed on the stage of a microscope adapted for high‐speed confocal imaging (488 nm ex, 510 nm emission; 8 frames/s). Endothelial Ca2+ dynamics were recorded at increasing flow rates (shear stress 0, 12, 52, 75, and 102 dynes/cm2). Image analysis was performed using ImageJ and custom software (LC_Pro) designed to discern distinct profiles of signal frequency, amplitude, duration and spatial spread. Artery segments were also subjected to immunostaining to assess relative expression and distribution of TRPV4 channels. We found that the wild type and TRPV4 knockouts both responded to shear stress. The TRPV4 knockout exhibited a reduced Ca2+ event frequency and shorter event durations compared to wild type controls in response to physiologic elevations in shear stress. Future experiments will focus on expounding upon the flow response, particularly the importance of TRPV4 channels in the time‐course of Ca2+ signal patterning changes under chronic low flow conditions.Support or Funding InformationSponsored by Mark Taylor and David Weber, Ph.D., Department of Physiology/Cell Biology, University of South Alabama College of Medicine, Mobile, AL. Summer Medical Student Research Program

Bioinspired, Artificial, Small-Diameter Vascular Grafts with Selective and Rapid Endothelialization Based on an Amniotic Membrane-Derived Hydrogel.

Clinical application of the amniotic membrane (AM) in vascular reconstruction was limited by poor processability, rapid biodegradation, and insufficient hemocompatibility. In this work, decellularized AM was digested to a thermosensitive hydrogel and densely cross-linked in the nanoscale as "enhanced" collagenous fibers. Via N-(3-dimehylaminopropyl)-N'-ethylcarbodiimide and N-hydroxysuccinimide (EDC/NHS) catalysis, REDV was further grafted to simulate anticoagulant substances on naturally derived blood vessels. This modification approach endowed AM with rapid endothelialization and rare vascular restenosis. Through adjusting the fixation condition, the pore size and mechanical stability of the fiber network were approximate to those of natural tissues and precisely designed to fit for cell adhesion. AM was synchronously fixed by alginate dialdehyde (ADA) and EDC/NHS, forming a "double-cross-linked" stable structure with significantly improved mechanical strength and resistance against enzymic degradation. The hemolytic and platelet adhesion test indicated that ADA/REDV-AM could inhibit hemolysis and coagulation. It also exhibited excellent cytocompatibility. It selectively accelerated adsorption and migration of endothelial cells (ECs) while impeding adhesion and proliferation of smooth muscle cells (SMCs). It maintained EC superiority in competitive growth and avoided thrombosis in vivo. Furthermore, its property of promoting reconstruction and repair of blood vessels was proved in an animal experiment. Overall, the present study demonstrates that ADA/REDV-AM has potential application as a small-diameter artificial vascular intima with rapid endothelialization and reduced SMC/platelet adhesion.

The atheroprotective roles of heart-protecting musk pills against atherosclerosis development in apolipoprotein E-deficient mice.

Heart-protecting musk pill (HMP), derived from Chinese herbal medicines, has been found to possess protective roles against atherosclerosis-related cardiovascular diseases (CVDs), however, the anti-atherosclerotic mechanisms of HMP are still unclear. Here, we investigated the effects of HMP on alleviating atherosclerotic lesion severity in mice and explored the molecular mechanisms. Apolipoprotein E-deficient mice were fed western-type diet supplemented with HMP (25 mg/kg/day) or normal saline gavage for 20 weeks. Then histopathological staining was performed to assess the atheromatous plaque burden. Biochemical kits were used to detect levels of lipid profiles. Moreover, effector factors associated with lipid metabolism in liver and intestinal tissues were investigated by western blot and real-time PCR assays. Levels of signal molecules participating in the mitochondrial-mediated apoptosis pathway were detected by Western blot. We found that HMP notably reduced atherosclerotic lesion size (P<0.05) and improved plaque stability (P<0.05). HMP treatment decreased circulating TC (P<0.01), LDL-C (P<0.01) and TG (P<0.05) levels and increased HDL-C (P<0.05) content. HMP was found to suppress SREBP2, HMGCR and PCSK9 expressions (P<0.05), yet promote LDLR expression (P<0.05) in hepatocytes. Moreover, HMP was discovered to activate PPARα/CPT-1A cascade (P<0.05) and inhibit contents of SREBP1c and the lipogenic genes FAS and ACCα (P<0.05). The LBK1/AMPK cascade was also activated after HMP administration (P<0.05). Additionally, HMP was found to facilitate transintestinal cholesterol excretion by increasing ABCG5 and ABCG8 levels and reducing NPC1L1 content (P<0.05). In terms of vasoprotective activities, we observed that HMP decreased cleaved caspase-3 content (P<0.05) in the vascular intima, which might be due to inhibition of mitochondrial-related signaling pathway. Altogether, our study indicates that HMP plays anti-atherosclerotic roles via regulating lipid metabolism and improving vascular intimal injury.

Smooth Muscle Progenitor Cells Preserve the Erectile Function by Reducing Corporal Smooth Muscle Cell Apoptosis after Bilateral Cavernous Nerve Crush Injury in Rats.

Radical prostatectomy causes erectile dysfunction (ED) and irreversible morphologic changes, including induction of endothelial and smooth muscle cell (SMC) apoptosis in the corpus cavernosum (CC). The injection of smooth muscle progenitor cells (SPCs) thickens the vascular intima and has demonstrated therapeutic benefit in cardiovascular disease animal. Herein, we investigated the effect of SPCs on the recovery of erectile function (EF) in rat models with bilateral cavernous nerve (CN) injury. Twenty-four male Sprague-Dawley rats were randomized into sham, vehicle only, or SPC treatment groups. Rats in the SPC treatment and vehicle groups were subjected to bilateral CN injury before intracavernosal injection. Intracavernosal injections of SPCs increased all EF parameters at day 28 after injury and simultaneously reduced apoptosis of the SMCs. Ultrastructural analysis revealed that SPCs maintained the integrity of the CC by preserving the structure of the adherens junctions. Tracking transplanted SPCs labeled with EdU showed that transplanted SPCs remained in the CC 28 days after treatment. Intracavernosal SPC injection restored EF after bilateral CN injury by reducing SMC apoptosis, which favored the maintenance of the structure of adherens junctions and regulated the stability of corporal vessels. These findings demonstrate the therapeutic potential of SPCs for treating ED in humans.

Sexual Dimorphism in Obesity-Associated Endothelial ENaC Activity and Stiffening in Mice.

Obesity and insulin resistance stiffen the vasculature, with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of women with obesity and insulin resistance to arterial stiffening may explain their heightened risk for CVD. However, the cellular mechanisms by which females are more vulnerable to arterial stiffening associated with obesity and insulin resistance remain largely unknown. In this study, we provide evidence that female mice are more susceptible to Western diet-induced endothelial cell stiffening compared with age-matched males. Mechanistically, we show that the increased stiffening of the vascular intima in Western diet-fed female mice is accompanied by enhanced epithelial sodium channel (ENaC) activity in endothelial cells (EnNaC). Our data further indicate that: (i) estrogen signaling through estrogen receptor α (ERα) increases EnNaC activity to a larger extent in females compared with males, (ii) estrogen-induced activation of EnNaC is mediated by the serum/glucocorticoid inducible kinase 1 (SGK-1), and (iii) estrogen signaling stiffens endothelial cells when nitric oxide is lacking and this stiffening effect can be reduced with amiloride, an ENaC inhibitor. In aggregate, we demonstrate a sexual dimorphism in obesity-associated endothelial stiffening, whereby females are more vulnerable than males. In females, endothelial stiffening with obesity may be attributed to estrogen signaling through the ERα-SGK-1-EnNaC axis, thus establishing a putative therapeutic target for female obesity-related vascular stiffening.

Id-1 Promotes Reendothelialization In The Early Phase After Vascular Injury Through Activation Of NFkB/survivin Signaling Pathway.

BackgroundPercutaneous coronary intervention (PCI) treatment can benefit patients, but also cause irreversible mechanical damage to the vascular endothelium, ultimately leading to restenosis of the target vessel. Thus, achieving rapid re-endothelialization and restoring the integrity of the vascular endothelium and function plays an important role in inhibiting neointimal hyperplasia and preventing restenosis. Id1 (inhibitor of DNA binding/differentiation factor 1) plays an important role in promoting cell proliferation and angiogenesis.Study objectiveThis study aims to investigate the relationship between Id1 and NFκB/survivin signaling pathways and their role in injured vascular repair by establishing a rat carotid balloon injury model.MethodsThe carotid artery model of rat balloon injury was established. The injured common carotid artery was obtained at different time points after vascular injury. RNA and protein were extracted and the mRNA and protein expression levels of Id1, NFκB and survivin were detected in vascular injury. The NFκB blocker BAY 11–7082 and survivin blocker YM155 were used and the effects of Id1, NFκB, survivin mRNA and protein expression, revascularization of blood vessels and neointimal responsiveness after vascular injury were observed in the vascular tissues of Ad-Id1 transfected balloon injury.ResultsId1, NFκB and survivin were expressed in injured rat carotid arteries. Overexpression of Id1 promoted re-endothelialization of injured vessels through NFκB/survivin signaling pathway, inhibited early vascular endometrial reactive hyperplasia; blocked NFκB the/survivin signaling pathway attenuates the re-endothelialization of Ad-Id1 and the early endothelium of Ad-Id1. Blocking the NFκB/survivin signaling pathway attenuates the re-endothelialization and early reactive hyperplasia of vascular intima of Ad-Id1.ConclusionNF-kappa B/survivin signaling pathway may play an important role in Id1 promoting vascular re-endothelialization, inhibiting neointimal hyperplasia and preventing vascular restenosis.

Potential role of Lu/BCAM in HIV-related atherosclerosis.

Atheromatous lesions are formed by macrophages and low-density lipoprotein cholesterol invading the vascular intima. Here we show that increasing cholesterol levels are associated with peripheral monocyte depletion and this imbalance is aggravated by carriage of Lu/BCAM leukocyte adhesion molecules. This is true only in HIV infection and probably explains the risk of atherosclerosis observed in HIV-positive patients.

Docosahexaenoic acid inhibits TNFα-induced ICAM-1 expression by activating PPARα and autophagy in human endothelial cells

Inflammation plays a key role in the development of cardiovascular disease (CVD), and docosahexaenoic acid (DHA) is recognized to fight against CVD. PPARα belongs to the nuclear hormone receptor superfamily and can interfere with inflammatory processes. Autophagy can degrade inflammasome proteins and counteract inflammation. Overexpression of intercellular adhesion molecule (ICAM) 1 in endothelial cells contributes to monocyte migration into the vascular intima. Here we investigated the mechanisms by which DHA inhibits TNFα-induced ICAM-1 expression in EA. hy926 endothelial cells. DHA markedly activated PPARα and suppressed TNFα-induced ICAM-1 expression, ICAM-1 promoter activity, p65 nuclear translocation, NFκB and DNA binding activity, and THP-1 cell adhesion. PPARα knockdown abolished the ability of DHA to inhibit TNFα-induced ICAM-1 expression and THP-1 cell adhesion. The PPARα antagonist GW6471 reversed the inhibitory effect of DHA on TNFα-induced ICAM-1 expression, p65 nuclear translocation, NFκB and DNA binding activity, and THP-1 cell adhesion. DHA significantly activated autophagy as evidenced by the formation of autophagosomes and increased LC3II protein expression. By contrast, wortmannin, which inhibits autophagy, abrogated DHA-induced autophagy and the inhibition of TNFα-induced ICAM-1 protein expression by DHA. Our results suggest that DHA likely inhibits TNFα-induced ICAM-1 expression by activating PPARα and autophagy.

Atorvastatin suppresses vascular hypersensitivity and remodeling induced by transient adventitial administration of lipopolysaccharide in rats.

The phenotypic transition of vascular smooth muscle cells (VSMCs) from a contractile to a proliferative state markedly affects the pathophysiology of cardiovascular diseases. The adventitial inflammation can promote neointimal formation and vascular remodeling. We used direct administration of lipopolysaccharide (LPS) into the periphery of the carotid artery to investigate the influence of transient adventitial inflammation on vascular remodeling and its potential mechanism. Male 15-week-old Wistar rats were randomly assigned to four groups with six rats in each group. The rats of groups I and II were administered distilled water, and group III and IV were treated with fasudil and atorvastatin respectively. All treatments were given daily for 11 days. On day 8, the adventitia in group I was injected with 5 µL sterile saline, and the group II-IV were injected with 5 µL sterilized LPS. The carotid blood flow and femoral blood pressure were measured in vivo, and the thickness of vascular intima and middle layer was measured in vitro. Serum interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) were determined using enzyme-linked immunosorbent assay (ELISA) assay. And the Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), myosin phosphatase target subunit 1 (MYPT1), myosin light chain (MLC), myocardin, SM-α actin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected by western blot. The comparisons were made by one-way analysis of variance with Bonferroni's post hoc test. A value of P<0.05 was considered to represent a statistically significant difference. Transient adventitial inflammation induced by LPS caused no obvious change in basal blood flow, but did lead to vascular hypersensitivity to serotonin. Morphological examinations revealed that the medial layer was the only domain affected, and showed VSMC proliferation and rearrangement. LPS increased serum IL-6 and TNFα contents, ROCK2 expression and activity, and caused changes in the expression levels of some stereotypical VSMC genes. Similar to the Rho-kinase inhibitor fasudil, atorvastatin completely restored the morphological alterations, even increased blood flow. Our study confirms the beneficial effect of atorvastatin on the vascular system in terms of morphology and function.

Giant cell arteritis without cranial manifestations caused mesenteric involvement: a case report

BackgroundGiant cell arteritis (GCA) is a granulomatous vasculitis and targets large vessels with predominance for the aortic arch and the cranial branches. GCA with cranial symptoms shows headache, jaw claudication, and ophthalmologic symptoms and thus was previously called temporal arteritis. Recently, cases of GCA without cranial manifestations and extracranial GCA have been reported.Case presentationA 76-year-old woman was referred to our hospital complaining of sudden abdominal pain and high fever. Her present history of illness did not show any cranial symptoms such as headache, visual disturbance, or stroke. CT images showed severe thickening of the small intestinal mesentery and massive ascites. She was diagnosed to have acute abdomen probably with gastrointestinal perforation and underwent the emergent laparotomy. Excisions of a 60-cm length of the jejunum including the thickening mesenteric lesion were carried out. Marked hypertrophy of the vascular intima and mild stenosis of the arterial lumen were displayed with infiltration of lymphocytes, neutrophils, and eosinophils. Scattered multinucleated giant cells on the endothelium, in the intima, media, and adventitia were demonstrated. Elastica van Gieson stain showed focal loss and fragmentation of the internal elastic lamina. Histopathological examinations showed typical GCA. Her postoperative process was uneventful without any symptoms, and she was followed as an out-patient prescribed with daily doses of 40 mg of prednisolone.ConclusionsWe hereby report a rare case of mesenteric involvement in GCA without cranial manifestations and elucidate the histopathological features of extracranial GCA in arteries as well as veins and jejunum.