Ultrastructural Study of Platelet Behavior and Interrelationship in Sprouting and Intussusceptive Angiogenesis during Arterial Intimal Thickening Formation.

Platelets in atherosclerosis, bypass stenosis, and restenosis have been extensively assessed. However, a sequential ultrastructural study of platelets in angiogenesis during the early phases of these lesions has received less attention. Our objective was the study of platelets in angiogenesis and vessel regression during intimal thickening (IT) formation, a precursor process of these occlusive vascular diseases. For this purpose, we used an experimental model of rat occluded arteries and procedures for ultrastructural observation. The results show (a) the absence of platelet adhesion in the de-endothelialized occluded arterial segment isolated from the circulation, (b) that intraarterial myriad platelets contributed from neovessels originated by sprouting angiogenesis from the periarterial microvasculature, (c) the association of platelets with blood components (fibrin, neutrophils, macrophages, and eosinophils) and non-polarized endothelial cells (ECs) forming aggregates (spheroids) in the arterial lumen, (d) the establishment of peg-and-socket junctions between platelets and polarized Ecs during intussusceptive angiogenesis originated from the EC aggregates, with the initial formation of IT, and (e) the aggregation of platelets in regressing neovessels ('transitory paracrine organoid') and IT increases. In conclusion, in sprouting and intussusceptive angiogenesis and vessel regression during IT formation, we contribute sequential ultrastructural findings on platelet behavior and relationships, which can be the basis for further studies using other procedures.

Some segmental morphological and morphometrical features of the intima and media of the aortic wall in Chinchilla lanigera.

BACKGROUND: The aim of this study is to describe the morphology, morphometry and ultrastructure of segments of the thoracic and abdominal aorta portions in Chinchilla lanigera. Thickness measurements of the tunica intima and media complex of the aorta were taken. MATERIALS AND METHODS: In all observed specimens, the thickness values for the tunica intima and media complex of the cranial thoracic aorta were significantly higher (mean: 702.19 µm) when compared to the values of other analysed aortic segments (means: 354.18 µm; 243.55 µm). Complex statistical methods were used to assess the differences between various aortic segments. RESULTS AND CONCLUSIONS: The components of the vessel walls show variations in structure and thickness, presumably due to an adaptation to functional demand.

Histochemical, immunohistochemical and ultrastructural analysis of aortic wall in neonatal coarctation.

The neonatal type of coarctation is characterized by the presence of the ductal sling and coarctational shelf placed proximally in relation to the ductal orifice. Those morphological features are not described in detail yet from immunohistochemical and transmission electron microscopy (TEM) aspects, so the aim of this study was to investigate the smooth muscle cells (SMCs) phenotype in aortic intimal thickening, presence of inflammatory cells and contents of intimal and medial, and adventitial connective tissue. We examined samples of coarctation segments excised at surgery after end-to-end anastomosis from 30 patients, ages from 14 days to three months, histochemicaly, immunocytochemically and by TEM. In all samples, it is noticed focal intimal thickening on the posterior aortic wall, with accumulation of SMCs, which show immunoreactivity on alpha-smooth muscle actin (α-SMA) and vimentin (but not on desmin) and also expressed proliferating cell nuclear antigen (PCNA) and S-100 protein. At TEM analysis, those SMCs show a fibroblast-like morphology, so their functions could be to proliferate and secrete extracellular matrix (ECM) components (a synthetic phenotype). In all studied samples of the coarctation, on the posterior wall, the immunocytochemical and TEM examination revealed the presence of SMCs of the synthetic phenotype. Results also showed an increase of the cell number in intima of this part of aortic wall, followed by proliferated SMCs in inner media and absence of inflammatory cells. This finding suggests that proliferation of the SMCs, their synthetic activity and increase of the cell number could lead to formation of the intimal thickening on the posterior wall.

Cross talk between TGF beta and TNF alfa in regression of myointimal hyperplasia.

BACKGROUND: The phenomena involved in regression of arterial myointimal hyperplasia have not been analyzed in detail. MATERIALS AND METHODS: In 24 Lewis rats, a 1-cm-long venous graft, obtained from syngenic Lewis rats, was implanted in the infrarenal aorta. After 4 wk, the grafts were removed and analyzed using scanning electron microscopy and histochemistry. The grafts showed evidence of myointimal hyperplasia; 16 of these explanted grafts were reimplanted in the vein circulation of syngenic Lewis rats. These grafts were harvested 2 wk (8 animals) and 8 wk (8 animals) later, showing complete regression of myointimal hyperplasia. RESULTS: Regression of experimental myointimal hyperplasia was correlated with the simultaneous and complementary action of Transforming Growth Factor beta and Tumor Necrosis Factor alfa. Inflammatory cytokines (IL1, IL2, and IL6) inhibit Tumor Necrosis Factor alfa-induced apoptosis. CONCLUSIONS: Regression of myointimal hyperplasia is an active process, which implies the action of several inhibitory factors. The analysis of these phenomena can lead to new therapeutic approaches to prevent myointimal hyperplasia progression.

Focal induction of ROS-release to trigger local vascular degeneration.

Reactive oxygen species (ROS) play an important role in the process of cardiovascular degeneration. We evaluated the potential of a controlled, local induction of ROS-release by application of rose bengal (RB) and photo energy to induce atherosclerosis-like focal vascular degeneration in vivo. After injection of RB, rats fed with a pro-degenerative diet underwent focal irradiation of the abdominal aorta by a green laser (ROS group), while the controls received irradiation without RB. Aortic tissue was analyzed by histology and immunohistochemistry at 0, 2, 4, 8, 28 and 56 days (n = 5). The intimal surface topography was analyzed by scanning electron microscopy. In the ROS group, an initial thrombus formation had disappeared by day 8. Similarly, ROS-derived products displayed the highest concentrations at day 0. Relative matrix metalloproteinase (MMP) activity achieved a maximum after 8 days (ROS group vs. CONTROL GROUP: 1.60 ± 0.11 vs. 0.98 ± 0.01; p < 0.001). After 28 days, no significant differences in any aspect were found between the ROS group and the controls. However, after 56 days, the aortic tissue of ROS animals exhibited relative media-pronounced thickening (ROS vs. CONTROL: 2.15 ± 0.19 vs. 0.87 ± 0.10; p < 0.001) with focal calcification and reduced expression of alpha smooth muscle actin (aSMA). The ROS-releasing application of RB and photo energy allowed for the induction of vascular degeneration in a rodent model. This protocol may be used for the focal induction of vascular disease without systemic side effects and can thereby elucidate the role of ROS in the multifactorial processes of vessel degeneration and atherogenesis.

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function.

Arterial reconstruction, whether angioplasty or bypass surgery, involves iatrogenic trauma causing endothelial disruption and vascular smooth muscle cell (VSMC) proliferation. Common murine models study small vessels such as the carotid and femoral arteries. Herein we describe an in vivo system in which both VSMC proliferation and endothelial barrier function can be simultaneously assessed in a large vessel. We studied the infrarenal aortic response to injury in C57BL/6 mice. The aorta was injured from the left renal vein to the aortic bifurcation by 30 transmural crushes of 5-seconds duration with a cotton-tipped applicator. Morphological changes were assessed with conventional histology. Aorta wall thickness was measured from the luminal surface to the adventitia. EdU integration and counter staining with DAPI and alpha-actin was used to demonstrate VSMC proliferation. Activation of ERK1/2, a known moderator of intimal hyperplasia formation, was determined by Western Blot analysis. The effect of inflammation was determined by immunohistochemistry for B-cells, T-cells, and macrophages. En face sections of endothelium were visualized with scanning electron microscopy (SEM). Endothelial barrier function was determined with Evans Blue staining. Transmural injury resulted in aortic wall thickening. This injury induced VSMC proliferation, most prominently at 3 days after injury, and early activation of ERK1/2 and decreased p27kip1 expression. Injury did not result in increased B-cells, T-cells, or macrophages infiltration in the vessel wall. Injury caused partial endothelial cell denudation and loss of cell-cell contact. Injury resulted in a significant loss of endothelial barrier function, which returned to baseline after seven days. The murine transmural blunt aortic injury model provides an efficient system to simultaneously study both VSMC proliferation and endothelial barrier function in a large vessel.

Ultrastructure of Pericystic or Intracystic Blood Vessels in Epidermoid Cysts-A Transmission Electron Microscopy Study: Laboratory Investigation.

OBJECTIVES: Recently, we reported a tendency toward spontaneous hemorrhage in both the preoperative and postoperative periods in patients with intracranial epidermoid cyst (EC). According to our experience, this tendency for spontaneous hemorrhage was partly caused by the pathologic blood vessels adjacent to the EC. This study was designed to testify this hypothesis. METHODS: Twenty-three removable pericystic or intracystic blood vessels from 17 patients with EC were collected during surgery and were then examined by transmission electron microscopy. The microvascular structure in gliomas was chosen as the control. RESULTS: Under electron microscopy, variant pathologic changes of vessels were found in all patients with EC. In the tunicae intima, we found vacuolization, apoptosis, necrosis, and intralumenal protrusion of endothelial cells, as well as swollen basement and highly flexed and discontinued elastic plate. In the tunicae media, vacuolization and swollen mitochondria were found in muscular cells. In the tunicae adventitia, extravascular erythrocytes, edema or apoptosis of pericytes, collagen predominance, and inflammatory cell infiltration and destruction were found. Neuron denature and necrosis were found in the peripheral brain tissue. In the microvascular structure of 5 glioma specimens, we found enlargement and hyperplasia of endothelial cells, swollen basement membrane, swollen pericytes, and astrocytic hyperplasia and neuron denature in adjacent brain tissues. CONCLUSIONS: Our findings provide strong evidence for the hypothesis that intracystic or pericystic vascular degeneration or destruction accounts for the spontaneous hemorrhage tendency before and after surgical resection of ECs.

Evaluation of synthetic vascular grafts in a mouse carotid grafting model.

Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

Bioinspired One-Dimensional Nano-Wrinkles Guide Liquid Behaviors at the Liquid-Solid Interfaces.

Learning from nature concerning how nanostructured surfaces interact with liquids may provide insight into better understanding of inside living biological interfaces bearing these nanostructures and further development of innovative materials contacting water. Here we investigate the dynamic behaviour of water droplet interacting with one-dimensional nano-wrinkles of different size on polydimethylsiloxane (PDMS) surface. The structure design of the variationally one-dimensional nano-wrinkles is inspired by in vivo responding topographic changes in aortic intima, which was characterized with liquid-phase atomic force microscopy. We show here that increasing the amplitude of the wrinkles promotes the spreading and energy dissipation of liquid droplets on the wrinkled interfaces. This result suggests a possible bio-protection mechanism of blood vessels via its structural changes on the aortic intima against elevated flowing blood, and provides a basis for tuning interfacial nanostructure of optimal durability against wearing by the liquid behaviors.

Effect of residual stress on peak cap stress in arteries.

Vulnerable plaques are a subset of atherosclerotic plaques that are prone to rupture when high stresses occur in the cap. The roles of residual stress, plaque morphology, and cap stiffness on the cap stress are not completely understood. Here, arteries are modeled within the framework of nonlinear elasticity as incompressible cylindrical structures that are residually stressed through differential growth. These structures are assumed to have a nonlinear, anisotropic, hyperelastic response to stresses in the media and adventitia layers and an isotropic response in the intima and necrotic layers. The effect of differential growth on the peak stress is explored in a simple, concentric geometry and it is shown that axial differential growth decreases the peak stress in the inner layer. Furthermore, morphological risk factors are explored. The peak stress in residually stressed cylinders is not greatly affected by changing the thickness of the intima. The thickness of the necrotic layer is shown to be the most important morphological feature that affects the peak stress in a residually stressed vessel.

Sildenafil stimulates and dexamethasone inhibits pulmonary vascular development in congenital diaphragmatic hernia rat lungs.

BACKGROUND: A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension. OBJECTIVE: To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs. METHODS: We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT). RESULTS: We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT. CONCLUSIONS: PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.

Internal mammary artery atherosclerosis: an ultrastructural study of two cases.

Atherosclerosis of the internal mammary artery (IMA) is generally regarded as a rare (but existent) pathological entity with only a few cases reported in the most recent literature. The only study which to our knowledge has investigated the ultrastructural features of IMA atherosclerosis, demonstrate the presence of endothelial cells loss, defects of internal elastic lamina with no evidence of lipid accumulation. In the present study, we describe two cases of IMA atherosclerosis in which ultrastructural analysis revealed the presence of a typical atherosclerotic plaque morphology with infiltration of inflammatory cells, formation of intraplaque lipid pools, and accumulation of lipid-laden foam cells throughout the thickened intima, never described in this rare lesion before. Microscopically, the lesions were also characterized by intimal thickening, invagination of endothelial cells, migration of smooth muscle cells with splitting, fenestration and/or fragmentation of the elastic sheets. Our observations add new data to the scarce and contradictory literature and to this largely understudied vascular disorder.

Morphometric study of aortic wall parameters evolution in newborn and child.

The largest artery in the human body, intimately connected to the heart, aorta is usually regarded as the major source of oxygenated blood for the circulatory system. The three concentric layers, which surround the aortic lumen-the tunics intima, media and adventitia, transform the aorta in a large elastic duct, which is irregular calibrated according to its segments. The special aortic distensibility is facilitated by its elastic circumferential lamellar complex. Any disturbance of its structural components is able to interfere with its normal and vital activity. Our study intends to reveal that the development of elastic lamellae should be regarded not only as an indispensable step for the aortic wall configuration, but also like a process in a firm connection with the rest of aortic wall components. The transition from intrauterine life to a new stage of life, childhood, has to determine an adequate adaptation of almost all the components of aortic wall, in order to sustain a consistent pulsatile blood flow. Stereological quantitative analysis of thoracic aortic fragments prelevated from newborns and children was performed in order to estimate the dynamic of vascular wall increase. We first estimated the general configuration of the thoracic aortic wall, quantifying the principal constituents; the connective tissue profile, investigated through its main elements, collagen and elastic fibers, supports the idea that each type of fiber has a distinct evolution in different groups of ages and has to be correlated with their involvement in maintaining of the aortic wall mechanical properties. Elastic fibers percentage volume was increased in both examined groups, with a small difference reported in children aorta, while collagen fibers exhibit a slow increase in children aorta. Our morphometric quantitative assessment suggests that further studies have to draw of in a precisely manner the outline of the secretory well defined function of vascular smooth muscle cells; the elucidation of the manner in which the secretory pathway for each type of fiber becomes fully adapted to every stage of aortic development will allow a new perspective in aortic pathology.

Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs.

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n = 26) versus 0 % (IR, 0; n = 12), p < 0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.

Changes of lysosomes in the earliest stages of the development of atherosclerosis.

One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the 'normal intima-initial lesion-fatty streak' sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease.

Histomorphometric study of intracranial internal carotid artery in man

The incidence of cerebrovascular diseases in man is on an increase. Atherosclerotic lesions in intracranial vessels are the usual cause. The normal parameters and histological changes in the intracranial internal carotid arteries, one of the feeder vessels to the brain, were studied in apparently healthy young adults of the Indian population. Gross and histomorphometric features of the intracavernous part of the internal carotid artery (ICA) were studied in the Indian population, in order to determine normal parameters, and observe structural changes in healthy young individuals. Length and outer diameter of ICA were taken in 100 autopsy cases. Cases were grouped according to age – Group I: <20 years, Group II: 20-40 years, and Group III: >40 years. Thirty pairs of vessels were processed for paraffin sectioning (young adults: 20-40 years). Seven-micrometers-thick transverse sections were stained with Hematoxylin and Eosin, Masson’s Trichrome and Verhoeff’s Stains. The length was found to be significantly greater on the left side in Groups II and III. The outer diameter was found to be significantly longer in the left side Group III. The mean thickness of tunica intima was found to be greater on the right side. Preatherosclerotic ageing changes were observed in the third decade of life in apparently healthy young individuals (AU)

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Increased shedding of microvesicles from intimal smooth muscle cells in athero-prone areas of the human aorta: implications for understanding of the predisease stage.

OBJECTIVE: This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage. METHODS: Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta. RESULTS: The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001). CONCLUSION: The present study supports the concept that alterations of the arterial intima occur at the predisease stage.

Ultrastructural features of human atherosclerosis.

Healthy human arteries are composed of three layers: the intima, the media, and the adventitia. Endothelial cells, which form the tunica intima, provide the physical interface between blood and surrounding tissue, regulate nutrient and blood component traffic, and participate in many physiologic events, such as hemostasis, inflammation, and angiogenesis. Within the tunica media, smooth muscle cells and extracellular matrix proteins, such as elastin, collagen, and proteoglycans, are quantitatively the largest components of the aortic vascular wall. The structural changes with atherosclerosis are currently considered degenerative phenomena, which primarily involve a sequence of reactions within the intima and include monocyte recruitment and macrophage formation, lipid deposition, smooth muscle cell migration, proliferation, and extracellular matrix synthesis. The molecular and cellular mechanisms underlying the disease cascade have been thoroughly investigated in experimental animals and cell culture, but the question of how these models can correctly mimic the human course of the disease remains open to debate. In the present review the basic structure of healthy human arteries and the pathological events occurring during the atherosclerotic process have been examined by both transmission and scanning electron microscopy. Human atherosclerotic lesions are presented and described in the following order: initial lesions, fatty dots and streaks, intermediate lesions, atheroma and fibrofatty plaques, and complicated lesions.

[Hepatic structure remodeling after an experimental pulmonary trunk stenosis and following its operative correction].

Changes in the liver were studied in 25 puppies with experimental pulmonary trunk stenosis of 6-12 months duration and 10 animals after the elimination of this defect. Control group included 10 dogs of the corresponding age. A complex of histological, morphometric, electron microscopic and immunohistochemical methods was used. During the modeling of pulmonary trunk stenosis, the resistance of hepatic afferent vessels to hepatic blood flow was increased due to the venous-arterial and venous-venous reactions. In the arteries, the bundles of smooth myocytes (SM) of the intimal muscle were formed together with the musculo-elastic sphincters, polypoid cushions, while in the branches of the portal vein, the intimal SM bundles and the valves appeared. In the efferent veins, the muscular elevations were hypertrophied. In all the vessels the thickening of the walls was observed, and in the media of the arteries, there were signs of sclerosis and the increased expression of alpha-smooth muscle actin (alpha-SMA). Hepatocytes demonstrated marked ultrastructural changes: mitochondrial matrix swelling, partial destructions of their cristae, dilation of endoplasmic reticulum cisterns. After the elimination of the defect, previously formed vascular adaptation reactions were found to disappear, the tone of the blood vessels in the liver decreased, causing the regression of hypertrophic changes of their media. The number of the arterial blood vessels with intimal muscle, sphincters and cushions decreased. The expression of alpha-SMA in the media of the arteries was also reduced. In hepatic efferent veins, the muscular elevations became attenuated. The dystrophic changes in hepatocytes regressed at both light-microscopic and the ultrastructural level.

Implication of vitamin A deficiency on vascular injury related to inflammation and oxidative stress. Effects on the ultrastructure of rat aorta.

BACKGROUND: Vitamin A deficiency induces activation of NF-kB and impairs activities of antioxidant enzymes in aorta. AIM OF THE STUDY: We study the effect of vitamin A deficiency on the aorta histoarchitecture and the possibly contribution of its prooxidant and inflammatory effects to artery alterations. METHODS: Twenty-one-day-old Wistar male rats were fed during 3 months with vitamin A-deficient diet (-A, n = 8) or the same diet containing 8 mg of retinol palmitate/kg of diet (+A, control, n = 8). In aortas, thiobarbituric reactive substances and reduced glutathione levels were measured by spectrophotometry. Expressions of TNF-alpha, NOX-2, VCAM-1, and TGF-beta1 were assessed by RT-PCR and Western Blot. The morphology of aorta was examined by light and transmission electron microscopy. RESULTS: In -A rats, high levels of TBARS in serum and aorta and low levels of GSH in aorta were found. An increased expression of TNF-alpha, NOX-2, VCAM-1, and TGF-beta1 in aorta from -A rats was observed. Examination of the intimal layer by light microscopy indicated the presence of an irregular surface in -A aortas. TEM studies showed large vacuoles and multivesicular bodies along the endothelium and also multivesicular bodies in the subendothelial space of aortas from -A rats. Furthermore, the histological appearance of internal elastic lamina was different from control. Small vesicles in the medial layer were observed in aortas from vitamin A-deficient rats. CONCLUSIONS: Vitamin A deficiency produces histoarchitectural alterations in aorta, which can be associated, at least in part, to the oxidative stress and inflammation induced by vitamin A deficiency.