Structural Changes In Blood Vessels Research Articles

Condition of the cardiovascular system in Wistar rats with experimental renal dysfunction

The aim: to evaluate functional and structural changes in blood vessels and myocardium in Wistar rats at different stages of the formation of experimental kidney dysfunction.Materials and Methods. Four groups of animals were studied. The first two groups consisted of rats subjected to 5/6 nephrectomy (NE). The period after NE is 2 or 4 months. The third and fourth groups included sham-operated (SO) animals of a similar observation period. After the end of the experiment, blood pressure was measured in rats, the left ventricular mass index (LVMI) was calculated, a biochemical blood test, histological, immunohistochemical and electron microscopic examination of the myocardium were performed, and the contractile activity of the portal vein was recorded for a period of 2 months (in vitro).Results. 2 months after NE, an increase in blood pressure, LVMI, and a decrease in the autorhythmic contractile activity of the portal vein were detected in rats. At the histological level, thickening of cardiomyocytes and arterial vessel walls and the presence of perivascular fibrosis were noted. After 4 months, in rats with NE, the increase in blood pressure, cardiomyocyte hypertrophy and perivascular fibrosis progressed. The thickness of cardiomyocytes was 14.1±3.11 μm, which was significantly greater than in the group with NE for 2 months (12.5±1.5 μm; p=0.008). At this period of observation, electron microscopic examination revealed deintegration of myofibrils, disruption of myofibril stacking and z-disk structure, and changes in the shape of mitochondria. 2 months after NE, an increase in the area of open capillaries was detected in rats (1902.8±202.9 μm²) compared to the corresponding LO animals (730.4±58.2 μm²; p=0.000). As renal dysfunction develops, the capillary area tends to increase (2139.1±396.5 μm²; p =0.120).Conclusion. In Wistar rats with renal dysfunction, changes were detected not only in the level of blood pressure, but also in the functional activity of the intravenous fluid, as well as in the structural components of the myocardium – cardiomyocytes, stroma and blood vessels. The increase in myocardial mass at the histological level was manifested by a significant increase in the thickness of cardiomyocytes, the volume of connective tissue, and the thickness of the wall of arterial vessels, reaching a maximum value at a longer period after NE.

Intra-Cranial Arterial Calcifications in Hemodialysis Patients.

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

Enlarged perivascular spaces are associated with white matter injury and cognition in an autosomal dominant vascular neurodegenerative disease (CADASIL)

AbstractBackgroundEnlarged perivascular spaces (EPVS), quantified on brain imaging, can reflect structural changes of blood vessels or of the surrounding fluid filled spaces. EPVS measures are emerging as promising biomarkers of cerebral small vessel disease, especially in dementia research. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a vascular neurodegenerative disease (VNDD) caused by mutations in the NOTCH3 gene. CADASIL involves disease of small vessels and presents with headaches, early onset strokes, and progressive neuropsychiatric dysfunction. We asked whether “burden” of EPVS is associated with clinical outcomes in CADASIL.MethodBrain MRIs were obtained in a CADASIL cohort (n = 27) and age/sex matched controls (n = 27). EPVS and WMH (white matter hyperintensity, measure of injury) were quantified with a semi‐ automated pipeline, using T1/T2 and FLAIR images, respectively. Participants underwent clinical and neuropsychological tests measuring executive function. Linear regression models were built to test associations between EPVS with WMH (a classical biomarker in CADASIL) and executive function. All models were adjusted for age and sex.ResultWe found no group differences in total EPVS volumes between CADASIL and the control group (β = 0.04, p = 0.73). Age was significantly associated with EPVS only in the control group (β = 0.018, p &lt; 0.05). We found a significant inverse association of EPVS with executive function in CADASIL (β = ‐0.11, p &lt; 0.05) and a positive association of EPVS with WMH (β = 0.28, p = 0.05).ConclusionCADASIL, a vasculo‐centric neurodegenerative disease includes prominent SVD pathology that may be driving total EPVS volumes. This may represent an accelerated vascular aging phenotype. Associations with cognition and MRI measure of white matter injury (WMH) in CADASIL confirm that EPVS may be a relevant biomarker to track in CADASIL. Longitudinal studies will be of great value in determining the utility of EPVS as a disease‐relevant biomarker in future therapeutic trials in CADASIL.

The Evolution of an Intramural Haematoma in Spontaneous Brachiocephalic Artery Dissection based on MRI Data

Dissection of the internal carotid (ICA) and vertebral arteries (VA) is one of the most common causes of ischaemic stroke in younger people. Despite wider use of modern neuroimaging techniques in clinical practice, and greater diagnostic capabilities for assessing structural changes in blood vessels, detection of spontaneous dissection remains low. The aim of the study was to identify patterns of change in the signal characteristics of an intramural haematoma in patients with spontaneous ICA and VA dissection on MRI and MR angiography (MRA), during the first three months after onset of clinical symptoms, as well as to create an optimal scan protocol. Based on changes in the K value and a visual assessment of the signal characteristics of the intramural haematoma, the study found that the signal intensity from the haematoma depends on the time of the examination. In the acute and chronic stages of dissection, the K value approaches 1 under Т1 FS and time-of-flight (TOF) MRA modes, and the intramural hematoma “merges” with the surrounding soft tissues, making it difficult to detect during these periods. Between 7 days and 2 months, the haematoma has a hyperintense signal and the K value is >1 under Т1 FS and TOF-MRA modes (p < 0.05). A comparison of K value data from different time periods made us add the T1 FS mode to the scan protocol for patients with suspected spontaneous dissection, in addition to the standard TOF-MRA, in order to improve the intramural haematoma imaging.

Characteristics of cerebral hemodynamics in patients with chronic brain ischemia

Background. Literature sources report conflicting results regarding the severity of clinical symptoms of hydrocephalus (HC) and their association with cerebral arterial blood flow (CABF); most studies do not show a direct relationship, while some suggest a link between clinical severity and progressive decrease in CABF. The study of hemodynamic changes in the brain of patients with chronic brain ischemia (CBI), elucidation of their relationship with cognitive impairments helps to improve diagnostic approaches and optimize the prognosis of the disease. The purpose of this study is to investigate the state of cerebral hemodynamics and to establish its relationship with changes in cognitive functions in patients with CBI and HC. Materials and Methods. A comprehensive examination of 110 patients with CBI and HC was performed. The localization of the HC and results of Montreal Cognitive Test (MoCA scale) were taken into account. Computed tomography of the brain was performed with subsequent determination of morphometric parameters and indices. The state of cerebral blood flow and structural changes of blood vessels were studied using transcranial color-coded duplex ultrasonography (TCCS) of intracranial vessels and extracranial divisions. Microsoft Excel 2011 and Statistica were used for statistical processing of the results. Results. It was found that there was a significantly larger diameter of both common carotid arteries (CCA), thickness of complex intima\media (CIM), maximum systolic velocity (Vs), velocity at the end of the diastolic cycle (Vd), as well as peripheral resistance (IR) in left CCA (p &lt;0,05) in patients with CBI and HC compared with patients with CBI without HC. Significantly larger diameter of left internal carotid artery (ICA), Vs, Vd and IR was revealed; Vs and Vd in the right ICA; Vd in the extracranial devision of vertebral artery (VA) in patients with HC. A significant relationship was found between the following blood flow parameters and the values of the MoCA scale: Vs MCA/MoCA (r = 0,45, p &lt;0,05), Vs ACA/MoCA (r = 0,38, p &lt;0.05), ICA diameter/MoCA (r = -0,51, p &lt;0,05). It was found that the diameter of CCA and the thickness of CIM were significantly larger in patients with CBI with internal HC in comparison with patients with CBI with external HC (p &lt;0,01). Vs and Vd in patients with internal hydrocephalus were significantly lower, and IR was significantly higher compared with patients with external hydrocephalus (p &lt;0,01). The diameter of ICA and IR in patients with CBI with internal HC was significantly higher, and Vs was significantly lower compared with patients with CBI and external HC (p &lt;0,01). Significantly different values were found in Vs and IR meanings in middle cerebral artery (MCA) and Vs in anterior cerebral artery (ACA) in patients with CBI with internal HC compared with patients with CBI with external HC.Conclusions. Functional parameters of blood flow and structural changes of cerebral arteries in patients with CBI with concomitant hydrocephalus differed significantly from those in patients without hydrocephalus and depended on the type and severity of hydrocephalus. ICA occlusion, ICA stenosis &gt;50%, and intracranial venous stasis were significantly more common in patients with severe and moderate HC compared with those with mild HC. A weak relationship was found between the structure of carotid arteries and blood flow in intracranial arteries in patients with CBI and HC. There was a significant relationship between blood flow indices and the values of the MoCA scale, which indicated the effect of changes in the vessels of the anterior circular basin on the cognitive functions and the lack of such connection with blood flow indices in vertebrobasilar basin.

The impact of harmful industrial factors on the reproductive health of workers in chemical production

In order to solve the demographic problems of the Russian Federation, the urgent task is to develop medical and preventive technologies for managing the reproductive health risks of chemical workers, and to reduce the risk of male and female infertility. 82 workers of chemical industries were examined. The indicators of specific hormonal status, immunological, genetic, parameters of functional studies, including the reproductive system, were studied. Class of working conditions by chemical factor 3.1 («harmful» with degree of harmfulness 1). In the structure of somatic diseases in women, endocrine pathology predominated (60 % of women in the observation group and 24 % of the comparison group), in men), inflammatory diseases of the genitourinary system (41.1 % and 46.6 %, respectively). Gynecological pathology in workers exposed to harmful chemicals was found 2 times more often than in the comparison group. Workers in the observation group revealed polymorphism of genes responsible for reproductive function. When exposed to a chemical factor, immunological disorders are formed in the form of a decrease in activation markers CD95 +, CD25 + (p &lt; 0.05); disorders of neuroendocrine regulation, hormonal dysfunction (decreased FSH in women and decreased testosterone, antisperm antibodies in men); increased content of tumor markers (CA-125 and CA-153); functional changes in the thyroid gland, structural changes in blood vessels, impaired reproductive function. Thus, exposure to production chemical factors of even low intensity contributes to the formation of hormonal and endocrine disorders, is an additional risk factor for miscarriage and the development of secondary infertility.

The Protective Role of Pentoxifylline on Diabetes-Induced Vasculopathy in the Male Albino Rat

Background: Diabetes mellitus is one of the chronic metabolic diseases, which affects about 450 million people in the world with one of them dies every 6 seconds from diabetic related macro and micro-vascular complications as cerebrovascular disease and nephropathy Aim of the work: This study was designed to investigate the protective effects of pentoxifylline (PTX) on macro-vascular complications as in aorta and renal artery in a streptozotocin induced diabetic rat model. Material and methods: Forty male albino rats randomly allocated into four groups ten rats each; group I(control group), group II (PTX group), group III (Diabetic group) and group IV (Diabetic + PTX group). Experimental diabetes was induced by single dose of streptozotocin (50 mg/kg) intraperitoneally. PTX and Diabetic + PTX groups received PTX in a single daily dose of (100 mg/kg) in the drinking water. At the end of the study, rats were anaesthetized and aorta and renal artery were extracted for H&E, Orecin and immunohistochemical stains to be examined by light microscope. Results: The main histological alterations in diabetic rat aorta and renal arteries were high significant thickening in the tunica media, smooth muscle proliferation, vacuolation, disruption of elastic fibers in aorta, strong positive reaction of tunica media by anti-NF-κb, and increased thickness of smooth muscle fibers by anti-α-SMA. The Diabetic group treated with pentoxifylline showed significant decrease in these findings. Conclusion: Pentoxifylline can ameliorate the structural changes in blood vessels resulting from diabetes mellitus.

Mechanisms behind Retinal Ganglion Cell Loss in Diabetes and Therapeutic Approach.

Diabetes produces several changes in the body triggered by high glycemia. Some of these changes include altered metabolism, structural changes in blood vessels and chronic inflammation. The eye and particularly the retinal ganglion cells (RGCs) are not spared, and the changes eventually lead to cell loss and visual function impairment. Understanding the mechanisms resulting in RGC damage and loss from diabetic retinopathy is essential to find an effective treatment. This review focuses mainly on the signaling pathways and molecules involved in RGC loss and the potential therapeutic approaches for the prevention of this cell death. Throughout the manuscript it became evident that multiple factors of different kind are responsible for RGC damage. This shows that new therapeutic agents targeting several factors at the same time are needed. Alpha-1 antitrypsin as an anti-inflammatory agent may become a suitable option for the treatment of RGC loss because of its beneficial interaction with several signaling pathways involved in RGC injury and inflammation. In conclusion, alpha-1 antitrypsin may become a potential therapeutic agent for the treatment of RGC loss and processes behind diabetic retinopathy.

Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications.

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ). The integrity of these bands would reflect the health of photoreceptors and retinal pigment epithelium. Moreover, we describe how the vascular plexuses vary in different regions of the healthy human and mice retina, using OCTA and immunohistochemistry. In humans, four, three, two or one plexuses can be observed depending on the distance from the fovea. Also, specific structures such as vascular loops in the intermediate capillary plexus, or spider-like structures of interconnected capillaries in the deep capillary plexus are found. In mice, three vascular plexuses occupy the whole retina, except in the most peripheral retina where only two plexuses are found. These morphological issues should be considered when assessing a pathology, as some retinal diseases are associated with structural changes in blood vessels. Therefore, the analysis of OCT bands and OCTA vascular plexuses may be complementary for the diagnosis and prognosis of retinal degenerative processes, useful to assess therapeutic approaches, and it is usually correlated to visual acuity.

AGE-RELATED MORPHOMETRIC CHARACTERISTICS OF REMODELING OF ARTERIAL BED OF HIND LIMBS IN WHITE RATS WITH EXPERIMENTAL HYPERCHOLESTEROLEMIA

Background. The human organism is constantly affected by metabolic risk factors. All of them for a long time are asymptomatic and often form in early childhood long before clinical manifestations. However, morphogenesis and morphofunctional features of age-related structural changes in blood vessels of different sites are poorly studied.Objective. To evaluate the morphometric characteristics of arterial bed remodeling of hind limbs in white rats of PRA and RA with experimentally induced hypercholesterolemia.Methods. The tissues biopsies from femoral, knee and shin areas were studied by means of histological and morphometric methods.Results. Experimental hypercholesterolemia caused remodeling of vessels with increasing thickness of medial and endothelial layer of vessels in the investigated parts of the rats’ body. In this case, the external diameter of vessels increased only in femoral area in the reproductive group of rats. In the group of pre-productive animals, the external diameter of the vessels studied was more or less unaffected. Thus, increased thickness of intima and media led to a decrease in arteries capacity. The depth of vascular lesions and the decrease in functional capacity of blood vessels were directly proportional to the duration of the experiment. In the group of reproductive rats, the changes in vascular bed were more evident.Conclusions. Objective study of the processes allows providing a scientific basis for further research and understanding of the pathomorphism of vascular diseases in humans.

Mineralocorticoid receptor: a critical player in vascular remodeling.

Vascular remodeling is a pathological condition with structural changes of blood vessels. Both inside-out and outside-in hypothesis have been put forward to describe mechanisms of vascular remodeling. An integrated model of these two hypotheses emphasizes the importance of immune cells such as monocytes/macrophages, T cells, and dendritic cells. These immune cells are at the center stage to orchestrate cellular proliferation, migration, and interactions of themselves and other vascular cells including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts. These changes on vascular wall lead to inflammation and oxidative stress that are largely responsible for vascular remodeling. Mineralocorticoid receptor (MR) is a classic nuclear receptor. MR agonist promotes inflammation and oxidative stress and therefore exacerbates vascular remodeling. Conversely, MR antagonists have the opposite effects. MR has direct roles on vascular cells through non-genomic or genomic actions to modulate inflammation and oxidative stress. Recent studies using genetic mouse models have revealed that MR in myeloid cells, VSMCs and ECs all contribute to vascular remodeling. In conclusion, data in the past years have demonstrated that MR is a critical control point in modulating vascular remodeling. Studies will continue to provide evidence with more detailed mechanisms to support this notion.

AB0630 Severity of Systemic Vasculitis in Rheumatoid Arthritis and Progressive Systemic Sclerosis – A Comparative Postmortem Study

BackgroundThe vascular system is the most important target of immunological processes, manifesting as vasculitis or characteristic structural changes of blood vessels. Vasculitis and/or structural changes of blood vessels are the...

Endothelin-1 Stimulates Connective Tissue Growth Factor Expression by Endothelial Cells,

Abstract 3265An important role for Endothelin-1 (ET-1) has been proposed in patients with sickle cell disease (SCD). We, and others, have reported that endothelin-1 (ET-1) receptor antagonists in vivo ameliorate numerous complications observed in sickle transgenic mice through mechanisms that remain unclear. ET-1 is a vasoconstrictor and important regulator of endothelial cells migration that promotes structural changes in blood vessels in response to increases in vasoactive hormones, growth factors, hypoxia, shear stress and free radicals; events commonly observed in patients with SCD. Endothelial cell activation is characterized in part by increases of cytokines and growth factors that are important in vascular maintenance and fibrogenesis such as connective tissue growth factor (CTGF). CTGF plays a role in blood vessel remodeling and fibrogenesis. Indeed, there is in vitro evidence that ET-1 stimulates the production of CTGF in smooth muscle cells. We hypothesized that increasing ET-1 would stimulate CTGF production and lead to endothelial cell activation. We studied the effects of ET-1 on the human endothelial cell line, EA.hy926 (EA), as well as in primary cultures of mouse aortic endothelial cells (MAEC). We analyzed the effects ET-1 on cytosolic Ca2+ levels by spectrofluorimetry of FURA-2AM loaded EA cells and noted that, as observed in fibroblasts, incubation with 10−8 M ET-1 led to increases in cytosolic Ca2+ levels that were blocked by pre-incubation with the ET-1 receptor B antagonist, BQ-788. We performed CTGF gene expression time course experiments (0, 2, 4, 8, 16, 24 Hr) on EA cells following incubation with 100 nM ET-1 using quantitative RT-PCR with TaqMan detection probes and GAPDH and beta-actin as endogenous controls. We observed increases of CTGF and VEGF expression between 4 and 8 hr for CTGF (1.74 fold increase vs time 0, n=6, P<0.03) and 4 hr for VEGF (2.14 fold increase vs time 0, n=3, P<0.04). Additional experiments on EA cells showed that incubation with 100 nM ET-1 for 4 hr in the presence of BQ123 and BQ788, two inhibitors of ET-1 type A and B receptors, respectively, blocked the ET-1 stimulated rises in CTGF and VEGF mRNA expression. We then performed western blot analyses and showed increases in cell-associated CTGF protein levels following incubation of EA cells with 10 nM ET-1 for 24 hr that were blocked by both BQ123 and BQ788. We then studied the effect of ET-1 on CTGF production in cell supernatants at various dose and time points by sandwich ELISA immunoassay. We observed increased levels of CTGF in cellular supernatants after 48 h of exposure that peaked at 10 nM ET-1 as compared to 24 h, 12 h and vehicle treated cells (P<0.001). To study whether the effects of ET-1 were unique to EA cells, we also analyzed the effects of ET-1 on early cultures of MAEC. Consistent with our observations in human EA cells, incubation of MAEC with 100 nM ET-1 for 4 hr was associated with increases of CTGF (1.86 fold vs vehicle, n=3, P<0.03) and was blocked by pre-incubation with BQ123 and BQ788. As CTGF has been shown to be chemotactic as well, we studied the effect of supernatants isolated from EA cells following stimulation with 10 nM ET-1 for 48 hrs on ex vivo human mononuclear cells (MNC) isolated from otherwise healthy subjects. We determined MNC transmigration by Cyquant fluorescence and observed enhanced migration of cells exposed to supernatants from ET-1-stimulated cells when compared to vehicle treatment that was significantly blunted by BQ123 and BQ788 pre-incubation. Further western blot analyses of the MNC that migrated following incubation with ET-1-stimulated supernatants showed the presence of CTGF in the MNC that otherwise do not express CTGF. Thus, we conclude that ET-1 leads to activation of endothelial cells and increases in CTGF from endothelial cells and suggest that therapies designed to block ET-1 receptors will also reduce endothelial cell activation in part by reducing CTGF production leading to alterations in cellular and tissue architecture. Disclosures:No relevant conflicts of interest to declare.

Role of Connective Tissue Growth Factor In Endothelin-Mediated Endothelial Cell Activation

AbstractAbstract 2107Endothelial cell activation and elevated levels of circulating Endothelin-1 (ET-1) have been reported in patients with atherosclerosis and sickle cell disease (SCD). ET-1 is a well-described vasoconstrictor, mitogen and regulator of endothelial cells migration that has been shown to promote structural changes in blood vessels. ET-1 is produced in response to increases in vasoactive hormones, growth factors, hypoxia, shear stress and free radicals, events that are commonly observed in patients with SCD. Endothelial cell activation is in part characterized by increases of cytokines such as monocyte chemotactic protein-1 (MCP-1) and growth factors that are important in vascular maintenance and fibrogenesis such as connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). CTGF and VEGF are important for blood vessel remodeling, fibrogenesis and angiogenesis. Indeed there is evidence that incubation of smooth muscle cells with ET-1 leads to increases in CTGF and VEGF levels. However, the relationship between ET-1 and CTGF in endothelial cell activation is unclear. We hypothesize that increasing ET-1 would stimulate CTGF production and endothelial cell activation. We studied the effects of ET-1 on the human endothelial cell line, EA.hy926 (EA), as well as in primary cultures of mouse aortic endothelial cells (MAEC). We performed gene expression time course experiments (0, 2, 4, 8, 16, 24 Hr) on EA cells following incubation with 100nM ET-1 using quantitative RT-PCR with Taqman chemistries and GAPDH and beta-actin as endogenous controls. We observed increases of CTGF and VEGF expression between 4 and 8 hr for CTGF (1.74 fold increase vs time 0, n=6, P<0.03) and 4 hr for VEGF (2.14 fold increase vs time 0, n=3, P<0.04). Additional experiments on EA cells showed that incubation with 100nM ET-1 for 4 hr in the presence of BQ123 and BQ788, two inhibitors of ET-1 type A and B receptors, respectively, blocked the ET-1 stimulated rises in CTGF and VEGF as well as MCP-1 expression. We then performed western blot analyses (Abcam-CTGF antibody ab6992; Abcam VEGF antibody ab1316) and showed increases in cell associated CTGF protein levels following incubation of EA cells with 100nM ET-1 for 24 hr. The ET-1 stimulated rise in CTGF levels were significantly blunted by pre-incubation of EA cells with both BQ788 and BQ123. To study whether the effects of ET-1 were unique to EA cells, we also analyzed the effects of ET-1 on early cultures of MAEC isolated from C57BLJ mice. Consistent with our observations in human endothelial cells, incubation of MAEC with 100nM ET-1 for 4 hr were associated with increases of CTGF and VEGF expression (1.86 fold vs vehicle, n=3, P<0.03; 1.73 fold vs vehicle, n=3 P<0.04 respectively). Furthermore, ET-1 stimulated rises in CTGF and VEGF expressions were likewise blocked by pre-incubation with BQ123 andBQ788. We conclude that addition of ET-1 leads to activation of endothelial cells and increases in CTGF and VEGF from human and mouse endothelial cells. Thus we suggest that therapies designed to block ET-1 receptors will reduce endothelial cell activation in part by reducing CTGF production leading to alterations in cellular and tissue architecture. This work was supported by NIH R01HL090632 to AR and R01HL096518 to JRR. Disclosures:No relevant conflicts of interest to declare.

Vascular Imaging Using Confocal Microscopy

Blood vessels are dynamic structures and capable of structural changes in response to various challenges, which is called vascular remodeling. Since vascular remodeling is important for cardiovascular pathophysiology, monitoring of structural changes of blood vessels has been drawn attention. Physiological methods allow gross vessel structure identification at physiological conditions, but technical constraints limit the analysis of detailed structure of blood vessels. For an analysis of blood vessels and its interaction to periendothelial cells, visualization of intact blood vessels with various thicknesses is critical. Recent development of confocal microscopy enables us to reveal three-dimensional structures of specimens by analyzing relatively thick specimens with optical sectioning. Especially the three-dimensional visualization combined with multi-fluorescent immunohistochemistry technique reveals the detailed structures of blood vessels as well as interactions between endothelial cells and periendothelial cells. Here we will discuss the application of confocal microscopy to imaging of blood vessels.

Pseudotumor of calcaneus: Treatment with radiotherapy and replacement therapy

American Journal of HematologyVolume 57, Issue 3 p. 263-264 Letter to the EditorFree Access Pseudotumor of calcaneus: Treatment with radiotherapy and replacement therapy Rajesh Kashyap, Corresponding Author Rajesh Kashyap Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaDepartment of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorJ.N. Sarangi, J.N. Sarangi Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorV.P. Choudhry, V.P. Choudhry Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRenu Saxena, Renu Saxena Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRajesh Malhotra, Rajesh Malhotra Department of Orthopedics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this author Rajesh Kashyap, Corresponding Author Rajesh Kashyap Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaDepartment of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorJ.N. Sarangi, J.N. Sarangi Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorV.P. Choudhry, V.P. Choudhry Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRenu Saxena, Renu Saxena Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRajesh Malhotra, Rajesh Malhotra Department of Orthopedics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1096-8652(199803)57:3<263::AID-AJH22>3.0.CO;2-ACitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Gillbert MS: Hemophilic pseudotumor. In KM Brenkhous, HC Hemuker (eds): “ Handbook of Hemophilia.” New York: Elsevier, 1975, p 435. 2 Krill CE, Mauer AM: Pseudotumors of calcaneus in christmas disease. J Pediatr 77: 848, 1970. 3 Reinhold HS: Structural changes in blood vessels. Curr Top Radiat Res Q 10: 58, 1974. 4 Castaneda VL, Parmley RT, Bozzini M, Feldmeir JJ: Radiotherapy of pseudotumors of bone in hemophiliacs with circulating inhibitors to factor VIII. Am J Hematol 36: 55, 1991. 5 Chen YF: Bilateral hemophilic pseudotumors of the calcaneus and cuboid treated by irradiation. J Bone J Surg 47A: 517, 1965. Citing Literature Volume57, Issue3March 1998Pages 263-264 ReferencesRelatedInformation

Pseudotumor of calcaneus: Treatment with radiotherapy and replacement therapy

American Journal of HematologyVolume 57, Issue 3 p. 263-264 Letter to the EditorFree Access Pseudotumor of calcaneus: Treatment with radiotherapy and replacement therapy Rajesh Kashyap, Corresponding Author Rajesh Kashyap Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaDepartment of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorJ.N. Sarangi, J.N. Sarangi Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorV.P. Choudhry, V.P. Choudhry Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRenu Saxena, Renu Saxena Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRajesh Malhotra, Rajesh Malhotra Department of Orthopedics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this author Rajesh Kashyap, Corresponding Author Rajesh Kashyap Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaDepartment of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorJ.N. Sarangi, J.N. Sarangi Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorV.P. Choudhry, V.P. Choudhry Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRenu Saxena, Renu Saxena Department of Hematology, All India, Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this authorRajesh Malhotra, Rajesh Malhotra Department of Orthopedics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, IndiaSearch for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1096-8652(199803)57:3<263::AID-AJH22>3.0.CO;2-ACitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Gillbert MS: Hemophilic pseudotumor. In KM Brenkhous, HC Hemuker (eds): “ Handbook of Hemophilia.” New York: Elsevier, 1975, p 435. 2 Krill CE, Mauer AM: Pseudotumors of calcaneus in christmas disease. J Pediatr 77: 848, 1970. 3 Reinhold HS: Structural changes in blood vessels. Curr Top Radiat Res Q 10: 58, 1974. 4 Castaneda VL, Parmley RT, Bozzini M, Feldmeir JJ: Radiotherapy of pseudotumors of bone in hemophiliacs with circulating inhibitors to factor VIII. Am J Hematol 36: 55, 1991. 5 Chen YF: Bilateral hemophilic pseudotumors of the calcaneus and cuboid treated by irradiation. J Bone J Surg 47A: 517, 1965. Citing Literature Volume57, Issue3March 1998Pages 263-264 ReferencesRelatedInformation

Structural changes in blood vessels entering the growth plate during growth in rats.

We observed the structural changes in blood vessels entering the growth plates of the femur and tibia of rats during growth using scanning electron microscopy. The penetrating vessels had blind endings which were bulbous at a time when rats showed rapid skeletal development. With subsequent slowing of development, the density of the vessels decreased and the blind endings became short stumps. These changes were more prominent in the proximal femur than in the distal femur and proximal tibia. The present study indicates an intimate relation between endochondral ossification in the growth plate and the structure of the penetrating vessels.

Nitric oxide in vascular remodeling.

Vascular remodeling is a series of structural changes in blood vessels. Therefore, it may be conceivable that any humoral factors and physical forces acting on the vascular wall are involved in the remodeling processes. Cells in the vascular wall respond to the humoral and physical factors and may induce extracellular matrix, cell adhesion molecules and other humoral factors. They even grow so that cellular and noncellular components deviate from the normal population. We discuss the relationship among nitric oxide (NO), pressure and growth of smooth muscles. Decreased NO may be a consequence as well as a cause of high pressure. Similarly, high pressure is a cause as well as a consequence of decreased NO. Remodeling could be a consequence of both high pressure and decreased NO. Thus, vascular remodeling is a complex dynamic state, where any causes and results are influenced by each other. Interaction of NO and pressure is one such complexity.

Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats.

In humans, aging produces many structural changes in blood vessels, one of the most pronounced being arterial calcium overload. Simultaneously arteries become increasingly rigid. The slow evolution of the two processes renders it difficult to evaluate the importance of vascular calcium overload in the development of decreased compliance. To gain insight into this relationship, rapid vascular calcium overload was produced by treating young rats with vitamin D3 and nicotine. When rats were allowed 16 days or longer to recover from such treatment, analysis of plasma parameters revealed no overt toxicity, and growth rate was similar to that of controls. Pronounced calcium overload was seen primarily in compliance arteries. Changes in systemic arterial compliance, characteristic impedance, pulse-wave velocity, and carotid compliance all reflected a substantial increase in arterial rigidity. Linear regression analysis revealed significant correlations between the various indicators of arterial distensibility and arterial calcium content. In conclusion, treatment of young rats with vitamin D3 and nicotine may provide a suitable model with which to investigate how calcium overload is involved in the induration of compliance arteries.