Tunica Media Of Arteries Research Articles

Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis.

BackgroundLong non-coding RNAs (lncRNAs) have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT), and evaluated its role and predicting ability in atherosclerotic development.MethodsAPPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP) or myocardial infarction (MI). Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI.ResultsAPPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT.ConclusionsThis study revealed that circulating lncRNA-APPAT may perform an important function and have some indicating ability on the development of atherosclerosis.

A cell-based mechanical model of coronary artery tunica media.

A three-dimensional cell-based mechanical model of coronary artery tunica media is proposed. The model is composed of spherical cells forming a hexagonal close-packed lattice. Tissue anisotropy is taken into account by varying interaction forces with the direction of intercellular connection. Several cell-centre interaction potentials for repulsion and attraction are considered, including the Hertz contact model and its neo-Hookean extension, the Johnson-Kendall-Roberts model of adhesive contact, and a wormlike chain model. The model is validated against data from in vitro uni-axial tension tests performed on dissected strips of tunica media. The wormlike chain potential in combination with the neo-Hookean Hertz contact model produces stress-stretch curves which represent the experimental data very well.

Elucidation of mechanism of blood-brain barrier damage for prevention and treatment of vascular dementia.

It is well-known that the blood-brain barrier (BBB) plays significant roles in transporting intravascular substances into the brain. The BBB in cerebral capillaries essentially impedes the influx of intravascular compounds from the blood to the brain, while nutritive substances, such as glucose, can be selectively transported through several types of influx transporters in endothelial cells. In the choroid plexus, intravascular substances can invade the parenchyma as fenestrations exist in endothelial cells of capillaries. However, the substances cannot invade the ventricles easily as there are tight junctions between epithelial cells in the choroid plexus. This restricted movement of the substances across the cytoplasm of the epithelial cells constitutes a blood-cerebrospinal fluid barrier (BCSFB). In the brain, there are circumventricular organs, in which the barrier function is imperfect in capillaries. Accordingly, it is reasonable to consider that intravascular substances can move in and around the parenchyma of the organs. Actually, it was reported in mice that intravascular substances moved in the corpus callosum, medial portions of the hippocampus, and periventricular areas via the subfornical organs or the choroid plexus. Regarding pathways of intracerebral interstitial and cerebrospinal fluids to the outside of the brain, two representative drainage pathways, or perivascular drainage and glymphatic pathways, are being established. The first is the pathway in a retrograde direction to the blood flow through the basement membrane in walls of cerebral capillaries, the tunica media of arteries, and the vessels walls of the internal carotid artery. The second is in an anterograde direction to blood flow through the para-arterial routes, aquaporin 4-dependent transport through the astroglial cytoplasm, and para-venous routes, and then the fluids drain into the subarachnoid CSF. These fluids are finally considered to drain into the cervical lymph nodes or veins. These clearance pathways may play a role in maintenance of the barrier in the entire brain. Obstruction of the passage of fluids through the perivascular drainage and glymphatic pathways as well as damage of the BBB and BCSFB may induce several kinds of brain disorders, such as vascular dementia. In this review, we focus on the relationship between damage of the barriers and the pathogenesis of vascular dementia and introduce recent findings including our experimental data using animal models.

Bridging the gaps at the physics-chemistry-biology interface.

It is commonly agreed that the most challenging problems in modern science and engineering involve the concurrent and nonlinear interaction of multiple phenomena, acting on a broad and disparate spectrum of scales in space and time. It is also understood that such phenomena lie at the interface

How many Layers has the Adventitia? - Structure of the Arterial Tunica Externa Revisited.

Tunica adventitia or tunica externa is the outer layer of the blood vessel wall. It consists of connective tissue with vasa and nervi vasorum and plays a key role in vascular health. The aim of our study was to compare the wall layers beyond tunica media in arteries of different type and location. The following arteries of pig, dog and cat were processed histologically and analysed by light microscopy: aorta ascendens, arcus aortae, aorta thoracica, aorta abdominalis, arteria (a.) femoralis, a.tibialis cranialis, a.carotis communis, a.lingualis, a.basilaris, a.cerebralis media, a.testicularis and aa.jejunales. We found two layers of connective tissue outside the media: (1) a compact layer with many elastic fibres in muscular and few in elastic arteries and (2) an outer layer of loose connective tissue. The compact layer was missing in aorta ascendens, arcus aortae and intracranial vessels. Adventitial stripping removed only the loose connective tissue layer. In spite of the still present compact layer, stripped arteries were very flimsy. We suggest using the term 'tunica externa' for the compact connective tissue layer and 'tunica adventitia' for the outermost loose connective tissue layer as in other organs. The presence of the tunica externa differs between species, arteries and arterial side, as well as the removability of tunica adventitia and tunica externa by anatomical dissection.

Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer’s disease, drug delivery to the brain and the concept of the Virchow–Robin space are discussed.

Matrix Gla-Protein (MGP) Not Only Inhibits Calcification in Large Arteries But Also May Be Renoprotective: Connecting the Dots

Matrix Gla-Protein (MGP) Not Only Inhibits Calcification in Large Arteries But Also May Be Renoprotective: Connecting the Dots

Radiographic manifestations of Mönckeberg arteriosclerosis in the head and neck region

Mönckeberg sclerosis is a disease of unknown etiology, characterized by dystrophic calcification within the arterial tunica media of the lower extremities leading to reduced arterial compliance. Medial calcinosis does not obstruct the lumina of the arteries, and therefore does not lead to symptoms or signs of limb or organ ischemia. Mönckeberg sclerosis most commonly occurs in aged and diabetic individuals and in patients on dialysis. Mönckeberg arteriosclerosis is frequently observed in the visceral arteries, and it can occur in the head and neck region as well. This report describes a remarkable case of Mönckeberg arteriosclerosis in the head and neck region as detected on dental imaging studies. To the best of our knowledge, this is the first case that has been reported in which this condition presented in the facial vasculature. The aim of this report was to define the radiographic characteristics of Mönckeberg arteriosclerosis in an effort to assist health care providers in diagnosing and managing this condition.

The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis

Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/− and TLR4−/− mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α (INF-α) secretion and increases cytotoxic activity of CD4+ T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease.

Frequência e fatores relacionados ao índice tornozelo-braquial aberrante em diabéticos

ResumoContextoO índice tornozelo-braquial (ITB) é um exame de rastreamento da doença arterial obstrutiva periférica, sendo também utilizado para avaliar o risco cardiovascular. Em diabéticos, a interpretação do exame é difícil pela possibilidade de índice aberrante devido à calcificação da camada média arterial.ObjetivoEncontrar a frequência de ITB aberrante em diabéticos e verificar sua associação com variáveis sociodemográficas.MétodosEstudo descritivo com entrevista e aferição de ITB de 309 pacientes diabéticos tipo 2, acompanhados no centro de referência Centro de Diabetes e Endocrinologia da Bahia (CEDEBA), Salvador, BA, Brasil. Foi estudada a frequência e a relação entre o ITB aberrante e variáveis sociodemográficas, como sexo, idade e renda familiar. Utilizou-se um ponto de corte para ITB aberrante de 1,3. As variáveis contínuas foram dicotomizadas. Para a análise estatística, utilizou-se o teste do qui-quadrado, considerando significante um p ≤ 0,05.ResultadosEntre os 309 pacientes entrevistados, 65% eram mulheres, 26% haviam cursado ensino médio completo e 77% tinham renda familiar igual ou menor que três salários mínimos. A frequência de ITB aberrante ≥ 1,3 foi 16,5%. Não foram encontradas correlações estatisticamente significantes nas análises bivariadas entre o ITB aberrante (≥ 1,3) e as variáveis sociodemográficas estudadas (sexo, idade, tempo de duração de diabetes melito, renda familiar e escolaridade).ConclusõesA frequência de ITB aberrante entre diabéticos foi de 16,5%. Não encontramos correlação entre as variáveis sociodemográficas (sexo, idade, tempo de DM, escolaridade e renda familiar) e a ocorrência de ITB aberrante.

Estudo comparativo do Índice Tornozelo-Braquial em diabéticos e não diabéticos com isquemia crítica

Resumo Contexto A calcificação da camada média arterial pode tornar o Índice Tornozelo-Braquial (ITB) falsamente elevado em diabéticos, dificultando a avaliação da doença arterial. Objetivo Comparar os valores do ITB de diabéticos e não diabéticos com isquemia crítica. Métodos Foram incluídos 140 pacientes (60% de diabéticos) acompanhados no Serviço de Cirurgia Vascular do Complexo Hospitalar Universitário Professor Edgard Santos com isquemia crítica por DAOP infra-inguinal. Comparou-se a média dos valores do ITB dos dois grupos de pacientes, correlacionando o ITB com a gravidade da isquemia, segundo a Classificação de Rutherford. A análise estatística foi realizada pelo EPI-INFO. Resultados A maioria dos 140 pacientes (77%) se encontrava na Categoria 5 da Classificação de Rutherford, 6% na 4 e 17% na 6. Nove diabéticos (11%) e um não diabético (2%) apresentaram ITB > 1,15 (p = 0,02), sendo excluídos da análise das médias do ITB. Considerando os 130 pacientes, os 75 doentes diabéticos apresentaram média do ITB na artéria tibial posterior de 0,26 versus 0,28 dos 55 doentes não diabéticos (p = 0,6); e no ITB da artéria pediosa aqueles apresentaram média de 0,32 versus 0,23 desses (p = 0,06). Estratificando os doentes nas categorias da Classificação de Rutherford, não houve diferença nas médias do ITB nas categorias 4 e 5. Apenas em relação à artéria pediosa e em pacientes na Categoria 6, a média do ITB foi significativamente maior em diabéticos (0,44 versus 0,16; p = 0,03). Conclusão Os diabéticos apresentaram maior prevalência de ITB falsamente elevado. Porém, excluindo-se esses casos, a média dos valores de ITB são semelhantes aos não diabéticos, exceto na artéria pediosa, nos pacientes com isquemia na categoria 6.

Presence and Distribution of the Vascularisation of Aortic Media in Some Mammals

It is well known that the large caliber vessels, the nutrition of the wall differs in the internal part in comparison to the external one. In the present study we assessed the presence and distribution of vascularisation of aortic media in 3 species: lamb, rabbit and chinchilla. Samples were harvested from a group of 3 animals for each species. After histological processing, we stained the sections and assessed the presence and distribution of vasa vasorum. In lamb, blood vessels were present in the media of the first aortic segments (with a larger caliber), and starting with abdominal descending aorta they were absent. In rabbit and chinchilla, blood vessels were not present in tunica media. The present study shows that vasa vasorum are present only in tunica media of arteries exceeding a certain caliber.

Thromboxane promotes smooth muscle phenotype commitment but not remodeling of hypoxic neonatal pulmonary artery.

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is characterized by vasoconstriction and pulmonary vascular remodeling. Remodeling is believed to be a response to physical or chemical stimuli including pro-mitotic inflammatory mediators such as thromboxane. Our objective was to examine the effects of hypoxia and thromboxane signaling ex vivo and in vitro on phenotype commitment, cell cycle entry, and proliferation of PPHN and control neonatal pulmonary artery (PA) myocytes in tissue culture.MethodsTo examine concurrent effects of hypoxia and thromboxane on myocyte growth, serum-fed first-passage newborn porcine PA myocytes were randomized into normoxic (21 % O2) or hypoxic (10 % O2) culture for 3 days, with daily addition of thromboxane mimetic U46619 (10−9 to 10−5 M) or diluent. Cell survival was detected by MTT assay. To determine the effect of chronic thromboxane exposure (versus whole serum) on activation of arterial remodeling, PPHN was induced in newborn piglets by a 3-day hypoxic exposure (FiO2 0.10); controls were 3 day-old normoxic and day 0 piglets. Third-generation PA were segmented and cultured for 3 days in physiologic buffer, Ham’s F-12 media (in the presence or absence of 10 % fetal calf serum), or media with 10−6 M U46619. DNA synthesis was measured by 3H-thymidine uptake, protein synthesis by 3H-leucine uptake, and proliferation by immunostaining for Ki67. Cell cycle entry was studied by laser scanning cytometry of nuclei in arterial tunica media after propidium iodide staining. Phenotype commitment was determined by immunostaining tunica media for myosin heavy chain and desmin, quantified by laser scanning cytometry.ResultsContractile and synthetic myocyte subpopulations had differing responses to thromboxane challenge. U46619 decreased proliferation of synthetic and contractile myocytes. PPHN arteries exhibited decreased protein synthesis under all culture conditions. Serum-supplemented PA treated with U46619 had decreased G1/G0 phase myocytes and an increase in S and G2/M. When serum-deprived, PPHN PA incubated with U46619 showed arrested cell cycle entry (increased G0/G1, decreased S and G2/M) and increased abundance of contractile phenotype markers.ConclusionsWe conclude that thromboxane does not initiate phenotypic dedifferentiation and proliferative activation in PPHN PA. Exposure to thromboxane triggers cell cycle exit and myocyte commitment to contractile phenotype.

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

Clearance of beta-amyloid in the brain.

Intravascular substances invade extracellular spaces in the brain via endothelial cells in the sites without bloodbrain barrier (BBB) and move not only in the cerebrospinal fluid (CSF) but also in the interstitial fluid (ISF) of brain parenchyma adjacent to non-BBB sites. It is likely that CSF drains directly into the blood via arachnoid villi and granulations and also to lymph nodes via subarachnoid spaces in the brain and nasal lymphatics, whereas ISF drains to cervical lymph nodes through pathways along vascular wall of capillaries and arteries. As the supposed pathways of fluids seem to be critical for the maintenance of normal brain function, it is reasonable to suspect that an obstacle to the passage of fluids through these pathways likely induces some kinds of brain dysfunction such as Alzheimer's disease. According to assumed pathways for the elimination of amyloid-β (Aβ) from the brain, Aβ peptides produced mainly in neurons are degraded by peptidases, flow out of the brain parenchyma into the blood through efflux transporters located in cerebral vessels, drain through perivascular pathways into the cervical lymph nodes, or are taken up by some kinds of cells in the brain. As for the perivascular pathways, ISF including Aβ peptides diffuses in the extracellular spaces of the brain parenchyma, enters basement membranes of capillaries, passes into the tunica media of arteries, and drains out of the brain. In this review, these pathways for the clearance of fluids including Aβ from the brain into the blood are briefly reviewed and the relationship between dysfunction of these pathways and brain diseases is discussed.

Mechanisms of Medial Arterial Calcification in Diabetes

Medial artery calcification (MAC) is a characteristic feature of diabetes. MAC represents a concentric calcification that proceeds via matrix vesicle-nucleated mineralization accompanied with apatitic calcium phosphate deposits in the arterial tunica media in the absence of atheroma and neointima. Multiple factors contribute to the induction and progression of diabetic MAC including inflammation, oxidative stress, adiposity, insulin resistance, advanced glycation end-products, and hyperphosphatemia. Osteoblast-like cells form in the vessel wall from vascular smooth muscle cells and multipotent vascular mesenchymal progenitors. These mineralizing cells as well as the recruitment of undifferentiated progenitors to the osteochondrocyte lineage play a critical role in the calcification process. Important transcription factors such as Msx 2, Osterix, and RUNX2 are crucial in the programming of osteogenesis. Currently, no therapy is available to reverse vascular calcification. Available therapies can only reduce and slow the progression of vascular calcification. Targeting regulatory proteins and enzymes directly involved in osteochondrogenesis and hydroxyapatite accumulation in the vascular wall may be beneficial for generating new efficient anti-calcific drugs.

Cor triatriatum sinister e hipertensão arterial pulmonar secundária em cão

This paper describes the occurrence of cor triatriatum sinister, a rare cardiac malformation in dogs, associated with pulmonary edema and pulmonary hypertension in a 5-year-old Poodle female with history of acute dyspnea and cyanosis. The animal presented acute respiratory failure, heart failure with low cardiac output, progressing to acute tubular necrosis and death. The diagnosis was made posmortem due to the clinical instability of the dog. This malformation was diagnosed by the subdivision of the left atrium into two compartments separated by an abnormal fibromuscular membrane, absence of structural abnormalities of the mitral valve and thickening of pulmonary artery tunica media associated with renal tubular degeneration. The occurrence of cor triatriatum in dogs is most common in the right atrium, defined as cor triatriatum dexter. Additionally, pulmonary arterial hypertension associated with this malformation is described only in humans with this heart defect.

Segmentation features and structural organization of the intrapulmonary artery of the yak

This study aims to systematically investigate intrapulmonary artery segmentation, blood vessel wall characteristics and structure organization, and the interrelation between intrapulmonary artery structure and plateau hypoxia adaptation in yak. The normal intrapulmonary artery structure of the yak had been studied using histological methods and transmission electron microscopy. The intrapulmonary artery of the yak was also examined using morphometric analysis and angiography. Results showed that the elastic intrapulmonary artery is divided into two types, namely, classical and transitional elastic segments. The muscular intrapulmonary artery is divided into three types, namely, transitional, classical muscular, and muscular arteriole segments. In the transitional elastic artery, elastic fibers and smooth muscles are linked through three models of ends, lateral branches, and branch tops. Two phenomena are possible for the transition from the elastic intrapulmonary artery to the muscular artery. One phenomenon postulates that a less elastic membrane is first increased and then suddenly decreased, and another supposes that the elastic membrane is gradually reduced and assembled in one to two layers before entering the transitional muscular artery. The smooth muscle of the intrapulmonary artery tunica media had more apophysis; it was physically connected with elastic membrane or fiber and composed of functionally resilient unit of the intrapulmonary arterial wall. Glycogenosomes increased in the muscular intrapulmonary artery smooth muscle cells. It exist one to two layers intact smooth muscle in intrapulmonary arteriole, the presence of intact smooth muscle in the intrapulmonary arteriole of the yak is a kind of structure adaptation to low-oxygen environment.

Circulation Research Thematic Synopsis

<i>Circulation Research</i> Thematic Synopsis

Circulation Research Thematic Synopsis

<i>Circulation Research</i> Thematic Synopsis