Vascular Wall Thickness Research Articles

Systematic and endothelial inflammation and endothelial progenitor cell levels in emphysematous rats exposed to intermittent hypoxia.

This study aimed to develop an overlap syndrome rat model with intermittent hypoxia (IH) exposure as seen in obstructive sleep apnea, on a base of preexisting emphysema caused by 16 wk of smoke exposure to determine whether IH and emphysema existing simultaneously play overlapped roles on systematic/endothelial inflammation and endothelial damage. Sixty male Wistar rats were divided into 4 groups of 15 each, labeled according to exposure conditions as control, IH, emphysema, and overlap groups. In these animals, electroencephalogram monitoring and preliminary experiments to obtain arterial blood gas values were performed. Serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6, TNF-α and IL-6 concentrations in the culture medium, Ras homology A mRNA expression levels of endothelial cells from right common carotid artery, and ratio of carotid intima-media thickness of whole thickness of vascular wall expressed in percent (C-IMT) (%) values were evaluated. Subsequently, circulating endothelial progenitor cells (EPCs) within rat peripheral blood and bone marrow were measured with flow cytometry. The serum and endothelial concentrations of TNF-α and IL-6 and the levels of endothelial Ras homology A mRNA have statistically significant results described as overlap>emphysema>IH>control. The levels of EPCs in rat peripheral blood and bone marrow have statistically significant results described as overlap>IH>emphysema>control. C-IMT (%) values from right common carotid artery are the highest in the overlap group and the lowest in the control group. There is no statistical difference when comparing the IH and the emphysema groups. Regardless of whether IH and emphysema exposure are mechanistically synergistic, this overlap elicits a more severe systematic/endothelial inflammation and endothelial damage; meanwhile, a robust mobilization of EPCs is demonstrated, which is not to mean a robust adherent and repairing capability.

Effect of angioprotectors on morphological changes in the lungs in COPD model

The aim of this study was to investigate morphological changes in the bronchi and the pulmonary arteries in the natural course of COPD and under treatment with angioprotective agents. Methods. COPD was modelled in rats by intermittent nitrogen dioxide inhalations for 60 days. Agents with angioprotective activity, such as rosuvastatin or sulodexide, were administered after the 30 th day of the exposure. Histological examination included morphometry. Results. The vascular wall thickness due to the media and the intima area enlargement was seen during COPD development without change in the vessel lumen. The Intima / media index also increased that is a typical sign of atherosclerotic lesion of the vascular wall. Pulmonary arteries diameter and the lumen size reduced under the treatment with sulodexide and rosuvastatin without any change in the vascular wall thickness but the intima / media index approached to the normal value. Conclusion. Ventilatory disorder progression in COPD is thought to be due to bronchial wall and lung remodeling such as sclerosis of the bronchial smooth muscle layer and occurrence of panacinar emphysema. Rosuvastatin improved pulmonary circulation and reduced lymphocytic infiltration of the large bronchi wall and the interalveolar septae. Positive effect of sulodexide on the pulmonary artery wall could be related to the presence of highly active heparin fraction in the drug structure that can improve the endothelial cell function. Agents with antithrombotic and angioprotective activity could slow COPD progression and of severe complication development.

Effects of chrysin (5,7-dihydroxyflavone) on vascular remodeling in hypoxia-induced pulmonary hypertension in rats.

BackgroundChrysin (5,7-dihydroxyflavone) inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation and arterial intima hyperplasia. This study aims to investigate the effects of chrysin on rat pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension (PH).MethodsSprague–Dawley rats were continuously exposed to 10% O2 for 4 weeks to induce PH. The effect of chrysin (50 or 100 mg/kg/d, subcutaneous) on vascular remodeling was investigated in hypoxia-induced PH model. At the end of the experiments, the indexes for pulmonary vascular remodeling and right ventricle hypertrophy were measured by vascular medial wall thickness and the ratio of right ventricle to (left ventricle plus septum). The expressions of NOX4, collagen I, and collagen III were analyzed by immunohistochemistry, real-time PCR, or western blotting. The proliferation of cultured pulmonary artery smooth muscle cells (PASMCs) was determined by BrdU incorporation and flow cytometry. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined by thiobarbituric acid reactive substances assay and 2′7′-dichlorofluorescein diacetate method.ResultsChrysin treatment for 4 weeks significantly attenuated pulmonary vascular remodeling and improved collagen accumulation and down-regulated collagen I and collagen III expressions, accompanied by downregulation of NOX4 expression in the pulmonary artery (P = 0.012 for 50 mg/kg/d, P < 0.001 for 100 mg/kg/d) and lung tissue (P = 0.026, P < 0.001). In vitro, chrysin (1, 10, and 100 μM) remarkably attenuated PASMC proliferation (P = 0.021 for 1 μM, P < 0.001 for 10 μM, and P < 0.001 for 100 μM), collagen I expression (P = 0.035, P < 0.001, and P < 0.001), and collagen III expression (P = 0.027, P < 0.001, and P < 0.001) induced by hypoxia, and these inhibitory effects of chrysin were accompanied by inhibition of NOX4 expression (P = 0.019, P < 0.001, and P < 0.001), ROS production (P = 0.038, P < 0.001, and P < 0.001), and MDA generation (P = 0.024, P < 0.001, and P < 0.001).ConclusionsThis study demonstrated that chrysin treatment in hypoxia-induced PH in rats reversed the hypoxia-induced (1) elevations of NOX4 expression, (2) productions of ROS and MDA, (3) proliferation of PASMC, and (4) accumulation of collagen.

Establishment of a rabbit model of coronary artery bypass graft and endothelial nitric oxide synthase gene transfection.

This study established an animal model of coronary artery bypass graft (CABG) surgery. The human endothelial nitric oxide synthase (eNOS) gene was transfected into grafted arterial walls to verify transfection efficiency. Forty rabbits were randomized into the following 4 equal groups: 1) eNOS gene transfection group (eNOS group); 2) empty eNOS gene transfection group (empty gene group); 3) control group; 4) normal femoral artery group. Grafted arteries, and normal carotid and femoral artery specimens were obtained 3 weeks later. Immunohistochemistry and analyses of tissue nitric oxide (NO) levels, eNOS activity, and eNOS protein western blotting were performed. The effectiveness and efficiency of transfection were observed and confirmed. All rabbits survived. The grafted arteries retained patency. Varying degrees of adaptability changes were observed in grafted arteries in each group. The eNOS group exhibited vascular wall thickening and significantly increased eNOS protein expression. The control and empty gene groups exhibited vessel wall degeneration, and eNOS protein was weakly or not expressed (P < 0.05). The arterial wall NO concentration and total eNOS activity in the eNOS group were significantly higher than those in the other groups (P < 0.05). Western blotting demonstrated that the vascular wall eNOS protein concentration was significantly greater than that in the other groups (P < 0.05). Furthermore, the eNOS gene transfection can increase eNOS expression and activity in vessel walls, increasing local NO concentration and expression.

Histological Changes in Some Organs of The Female Rats Infected With Toxoplasma Gondii Parasite Isolated From Embryo of Aborted Sheep

The current study included identifying the lesions and the histological changes caused by the intracellular parasite Toxoplasma gondii, which was isolated from embryos of aborted ewes. Intraperitonially injected in 15 female albino rats (3 months old) with suspension containing 100 tissue cysts.Histological section showed after four months of injection a chronic infection characterized by autolysis in all sections, where the liver sections showed expansion in the central hepatic veins, congestion in sinusoidal curves with irregularity in hepatic cords, and the presence of parasites in the liver cells. The brain tissue showed vacuoles in the neurons with an increase in the number of Purkenji cells. Kidney sections were characterized by degenerative and necrotic changes in the endothelial cells of the proximal and distal convoluted tubules with Sloughing of necrotic and degenerated cells of the tubes which accumulated inside the cavity. The parasites appeared in the endothelial cells of the glomerular tufts. Ovary and the uterus showed increased vascular wall thickness, furthermore, the spleen showed autolytic changes, deposition of pigment with the presence of parasites within the cells.

Are myofibroblasts activated in idiopathic carpal tunnel syndrome? an immunohistochemical study.

This study aims to investigate whether myofibroblasts participate in the fibrotic process of idiopathic carpal tunnel syndrome (CTS). Forty patients (12 males, 28 females; median age 50.85 ± 11.2 years; range 30 to 71 years) who were operated in our clinic between March 2010 and August 2010 were included in the study. Twenty-five idiopathic CTS patients were assigned to the study group, and 15 trauma patients were assigned to the control group. Samples were taken from both transverse carpal ligament and subsynovial connective tissue (SSCT) of participants and they were analyzed by immunohistochemical method. Four immunohistochemical markers were used to analyze myofibroblast existence and vascular wall thickness (alpha smooth muscle actin [α-SMA]), collagen type IV antibodies, and T (CD3) and B (CD20) lymphocytes. The existence of myofibroblasts (α-SMA) in SSCT of patients who were in early phase of idiopathic CTS was shown through the positive reaction of their antibodies with fibroblasts. A significantly increased reaction of α-SMA and collagen antibodies in vascular structure of SSCT demonstrated increased vascular wall thickness and vascularity in the study group (p<0.01). No significant difference was detected between the two groups in terms of T and B lymphocyte antibody reaction (inflammation). The findings of this study indicate a potential for myofibroblasts to be activated during the early phase of the disease and contribute to the onset of disease. Further studies with larger sample sizes would be of great assistance in determining the role of myofibroblasts in idiopathic CTS.

S34 Bmpr-ii Deficiency Leads To An Increase In Lung Egg Deposition, Pulmonary Vascular Remodelling And An Abnormal Liver Vasculature In Mice Chronically Infected With S. Mansoni

Rationale and objectives Schistosomiasis is the world-wide leading cause of pulmonary arterial hypertension (PAH) and is particularly prevalent in developing countries. More than 80% of patients with familial PAH in the western-world have a mutation in bone morphogenetic protein type-II receptor (BMPR-II), which is a member of the transforming growth receptor-beta (TGF-b) superfamily and is important in cell proliferation and differentiation. The aim of the study was to determine if mice with a heterozygous null mutation in BMPR-II are more susceptible to pulmonary vascular remodelling induced by S. mansoni infection, compared with wild-type littermates. Methods Wild-type (BMPR-II+/+) and BMPR-II heterozygous (BMPR-II+/-) C57/BL6 mice were infected percutaneously with S. mansoni . Seventeen weeks post-infection right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), liver and lung egg counts were measured. Pulmonary vascular remodelling and liver histology were assessed by morphometry, following immunohistochemistry. Lung, liver and serum cytokines were also measured. A macrophage phagocytosis assay and in vivo bead assay were also performed. Measurements and main results At 17 weeks post-infection there was a significant increase in pulmonary vascular remodelling associated with a significant increase in egg deposition and cytokines in the lung, in BMPR-II+/- mice. Furthermore, there was a positive correlation between lung egg deposition and pulmonary vascular wall thickness. Additionally, there was a significant dilatation of the central hepatic vein in the BMPR-II+/- infected mice compared with the BMPR-II+/+ infected mice. However, no differences in RVSP, RVH or liver egg deposition were found. Conclusions This study has shown that mice deficient in BMPR-II are more susceptible to pulmonary vascular remodelling induced by S. mansoni which is directly correlated to an increase in egg burden in these mice. Additionally, we have shown that BMPR-II+/- mice have an abnormal liver vasculature, which may be responsible for increased egg shunting into the lungs.

Cardiovascular effects of aerobic exercise training in formerly preeclamptic women and healthy parous control subjects

Women who have had preeclampsia demonstrate higher prevalence of metabolic syndrome (MetS), impaired vascular function, and increased sympathetic activity and are at increased risk of cardiovascular disease. The aim of this study was to assess the effects of 12 weeks of exercise training (70-80% maximum volume of oxygen utilization) in women who had had preeclampsia on physical fitness, components of MetS, vasculature, and autonomic functions compared with healthy control subjects. Our prospective case-control study included 24 normotensive women who had had preeclampsia and 20 control subjects who were matched for age and postpartum interval (all 6-12 months after delivery). Before and after training, we measured all components of MetS (ie, BP, lipids, glucose/insulin, and albuminuria), carotid intima media thickness (IMT) and brachial and superficial femoral artery endothelial function that used flow-mediated dilation (FMD). Autonomic activity was quantified with power spectral analysis (low-frequency/high-frequency power [LF/HF] ratio). At baseline, women who had had preeclampsia demonstrated higher values of most components of MetS. Compared with the control subjects, women who had had preeclampsia had increased IMT (580 ± 92 μm vs 477 ± 65 μm, respectively), impaired endothelial function (FMD brachial artery, 5.3% ± 2.2% vs 10.8% ± 3.5%, respectively; FMD superficial femoral artery, 4.9% ± 2.1% vs 8.7% ± 3.2%, respectively) and increased LF/HF power ratio (2.2 ± 1.0 vs 1.3 ± 0.4, respectively; all P < .05). In both groups, exercise training decreased values of most components of MetS and IMT, improved FMD, and concurrently reduced LF/HF. Despite these improvements, vascular and autonomic variables did not normalize by 12 weeks of training in women who had had preeclampsia. This study demonstrates that exercise training in women who had had preeclampsia and control subjects improves components of MetS, endothelial function, vascular wall thickness, and autonomic control. Nonetheless, trained women who had had preeclampsia only reached a cardiovascular status that is comparable with sedentary healthy control subjects.

Mechanisms of the Inward Remodeling Process in Resistance Vessels: Is the Actin Cytoskeleton Involved?

The resistance arteries and arterioles are the vascular components of the circulatory system where the greatest drop in blood pressure takes place. Consequently, these vessels play a preponderant role in the regulation of blood flow and the modulation of blood pressure. For this reason, the inward remodeling process of the resistance vasculature, as it occurs in hypertension, has profound consequences on the incidence of life-threatening cardiovascular events. In this manuscript, we review some of the most prominent characteristics of inwardly remodeled resistance arteries including their changes in vascular passive diameter, wall thickness, and elastic properties. Then, we explore the known contribution of the different components of the vascular wall to the characteristics of inwardly remodeled vessels, and pay particular attention to the role the vascular smooth muscle actin cytoskeleton may play on the initial stages of the remodeling process. We end by proposing potential ways by which many of the factors and mechanisms known to participate in the inward remodeling process may be associated with cytoskeletal modifications and participate in reducing the passive diameter of resistance vessels.

Pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow

Objective To study the pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow. Methods Sixty-five male or female Sprague-Dawley rats (180-230 g) were used and randomly divided into 3 groups: normal group(n=20); sham group(n=20), only exposing the abdominal aorta and inferior vena cava about 10-20 minutes; model group(n=25), rats in this group were subjected to an abdominal aorta-inferior vena cava shunt to create animal models of high pulmonary.After operation, all the rats were reared under the same conditions for 11 weeks.Then, the systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) of every rat were determined by means of homemade right heart catheterization.After that, the right ventricle (RV) was separated from the left ventricle (LV) and septum (S), then weighed.And right ventricular hypertrophy index (RVHI) was measured by the ratio of RV to LV+ S [RV/(LV+ S)]. In addition, the morphological changes of pulmonary interstitial of rats were observed under optical microscope by means of hematoxylin-eosin (HE) staining.In the end, single pulmonary artery smooth muscle cell (PASMC) was isolated through acute enzyme separation.Then membrane capacitance (Cm) was recorded through in the method of patch clamp technique. Results 1.Compared with sham group and normal group, the sPAP, mPAP and RVHI of model group increased significantly(F= 17.293, 16.259, 12.878, all P<0.01).2.In contrast to sham group and normal group, arterial wall area/vessel area(W/V) and arterial wall thickness/vessel external diameter(T/D) in model group increased significantly(F=85.717, 22.795, all P<0.01).3.The membrane capacitance of model group was bigger than that of sham group and normal group(F=8.704, P<0.01).4.mPAP was positively correlated with W/V, T/D and Cm(r=0.669, 0.662, 0.663, all P<0.01). Conclusions Shunts from abdominal aorta-inferior vena cava in SD rats caused high pulmonary blood flow-induced pulmonary hypertension, and these rats appeared with pulmonary smooth muscle cells hypertrophy, pulmonary vascular wall thickening and inflammatory cells infiltration. Key words: High pulmonary blood flow; Pulmonary arterial hypertension; Pulmonary interstitial

Wall shear stress in the stented superficial femoral artery in peripheral arterial disease

ObjectiveLocal changes in wall shear stress (WSS) contribute to vascular wall thickening and subsequent stenosis. Restenosis after stenting is a major concern, especially in the superficial femoral artery (SFA) of patients with peripheral arterial disease (PAD). Local alterations in WSS after stenting might contribute to restenosis/reocclusion. To test the hypothesis that WSS is impaired along the stented SFA segment, we studied the profile of WSS along the femoro-popliteal axis after stent placement in a cross-sectional design. MethodsEighty-seven patients with PAD (89 limbs) were included one day after stenting of the SFA. Flow velocities (peak and mean) and vessel diameter were measured by duplex ultrasound in five predefined segments along the femoro-popliteal axis, at rest and after exercise (30 toe raises); WSS (peak and mean) was calculated from flow velocities, vessel diameter and whole blood viscosity. ResultsWSS progressively declined along the stented segment at rest (peak WSS, p < 0.0001; mean WSS, p < 0.05); after exercise, WSS increased in all segments (all p < 0.001), but, again, progressively declined along the stent (peak WSS, p < 0.0001; mean WSS, p < 0.05). The internal vessel diameter remained unchanged after exercise in the stented and in the non-stented parts of the femoro-popliteal axis (all p > 0.05). ConclusionIn PAD patients with SFA stenting WSS is impaired along the femoro-popliteal axis. The consequences of this finding in terms of local effects on the vessel wall that might favor restenosis/reocclusion needs further investigation.

The effect of copper on vasospastic femoral artery in rats.

The aim of this study was to investigate the effect of copper, which is the cofactor and regulator of the superoxide dysmutase enzyme, on preventing experimental peripheral vasospasm in rats through antioxidative mechanisms. Twenty-four female Wistar-Albino rats were divided into 3 groups: group 1 (n=8), control group; group 2 (n=8), vasospasm group; and group 3 (n=8), vasospasm + copper treatment group. Morphometric measurements of wall thickness and lumen diameter of femoral arteries were performed. Statistical comparison of groups 1 and 2, regarding thickness of vascular walls, revealed a significant increase in group 2 (p=0.037) and regarding lumen diameters, revealed a significant decrease in group 2 (p=0.043). Comparison of diameters of the vascular lumen of groups 1 and 3 showed no significant difference (p=0.19), whereas the comparison of the thicknesses of the vascular walls displayed a significant increase in group 3 (p=0.028). Comparison of groups 2 and 3 regarding diameter of vascular lumens showed a significant decrease in group 2 (p=0.042), whereas group 3 displayed a significant decrease, in terms of thickness of the vascular walls (p=0.029). This study showed quantitatively that copper could prevent the development of experimental peripheral vasospasm in rats.

Vascular and antioxidant effects of an aqueous Mentha cordifolia extract in experimental N(G)-nitro-L-arginine methyl ester-induced hypertension.

The effect of an aqueous Mentha cordifolia (MC) extract on the haemodynamic status, vascular remodeling, function, and oxidative status in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was investigated. Male Sprague-Dawley rats were given L-NAME [50 mg/(kg body weight (BW) d)] in their drinking water for 5 weeks and were treated by intragastric administration with the MC extract [200 mg/(kgBWd)] for 2 consecutive weeks. Quercetin [25 mg/(kg BW d)] was used as a positive control. The effects of the MC extract on the haemodynamic status, thoracic aortic wall thickness, and oxidative stress markers were determined, and the vasorelaxant activity of the MC extract was tested in isolated mesenteric vascular beds in rats. Significant increases in the mean arterial pressure (MAP), heart rate (HR), hind limb vascular resistance (HVR), wall thickness, and cross-sectional area of the thoracic aorta, as well as oxidative stress markers were found in the L-NAME-treated group compared to the control (P < 0.05). MAP, HVR, wall thickness, cross-sectional area of the thoracic aorta, plasma malondialdehyde (MDA), and vascular superoxide anion production were significantly reduced in L-NAME hypersensitive rats treated with the MC extract or quercetin. Furthermore, the MC extract induced vasorelaxation in the pre-constricted mesenteric vascular bed with intact and denuded endothelium of normotensive and hypertensive rats. Our results suggest that the MC extract exhibits an antihypertensive effect via its antioxidant capacity, vasodilator property, and reduced vascular remodeling.

Doppler ultrasound detection of preclinical changes in foot arteries in early stage of type 2 diabetes.

SummaryBackgroundThere are few reports regarding the changes within the vessels in the initial stage of type 2 diabetes. The aim of this study was to estimate the hemodynamic and morphological parameters in foot arteries in type 2 diabetes subjects and to compare these parameters to those obtained in a control group of healthy volunteers.Material/MethodsUltrasound B-mode, color Doppler and pulse wave Doppler imaging of foot arteries was conducted in 37 diabetic patients and 36 non-diabetic subjects to determine their morphological (total vascular diameter and flow lumen diameter) and functional parameters (spectral analysis).ResultsIn diabetic patients, the overall vascular diameter and wall thickness were statistically significantly larger when compared to the control group in the right dorsalis pedis artery (P=0.01; P=0.001), left dorsalis pedis artery (P=0.007; P=0.006), right posterior tibial artery (P=0.005; P=0.0005), and left posterior tibial artery (P=0.007; P=0.0002). No significant differences were observed in both groups in flow lumen diameters and blood flow parameters (PSV, EDV, PI, RI). In the diabetic group, the level of HbA1c positively correlated with flow resistance index in the right dorsalis pedis artery (r=0.38; P=0.02), right posterior tibial artery (r=0.38; P=0.02) and left posterior tibial artery (r=0.42; P=0.009). The pulsatility index within the dorsalis pedis artery decreased with increased trophic skin changes (r=–0.431, P=0.009).ConclusionsIn the diabetic group, overall artery diameters larger than and flow lumina comparable to the control group suggest vessel wall thickening occurring in the early stage of diabetes. Doppler flow parameters are comparable in both groups. In the diabetic group, the level of HbA1c positively correlated with flow resistance index and negative correlation was observed between the intensity of trophic skin changes and the pulsatility index.

ACE I/D Gene Polymorphism in Children with Family History of Premature Coronary Disease.

Letter to the editor regarding the article by de Albuquerque et al: Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. I read with interest the recent review article by de Albuquerque et al1 published in the Arquivos Brasileiros de Cardiologia entitled “Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.” They showed that the DD genotype of Angiotensin-converting enzyme (ACE) gene polymorphism was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile1. Atherosclerosis, the major cause of CAD, manifests clinically in adulthood. However, this disease begins very early in life, often during childhood. Genetic and environmental factors, gene–environment interaction effects also come into play in the development of atherosclerosis. Family history is the most significant independent risk factor for CAD. In our study, we included a total of 140 children, 72 males and 68 females between the ages of 4.9 and 15.7 years. Among these children, 73 had a parental history of premature CAD (parents have been diagnosed with the CAD by coronary angiographic study, ages below 55 for men and 65 for women) and the rest of 67 belonged to our control group (parents have shown normal coronary angiographic study). The participants were screened for the mutations ACE I/D gene polymorphisms. The genotypes of ACE I/D were significantly different between the study and control groups (p = 0.01). The frequency of D/D genotype was significantly higher in the study group than the control group (respectively, 20/73 vs. 3/67, p = 0.01) (Table 1). The frequency of the D allele was slightly higher in study group (0.52) than in control group (0.27) (p = 0.005). Table 1 The frequencies of the ACE I/D gene polymorphisms in study group and control group, and the odds ratios with 95% CI The angiotensin converting enzyme is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. The ACE insertion/deletion (I/D) polymorphism results from the absence or presence of an alu repeat located in intron 16 of the ACE gene. The D allele of an insertion/deletion (I/D) polymorphism of the gene encoding ACE is associated with higher plasma ACE concentrations2. Many studies have investigated the association between the DD genotype of ACE gene I/D polymorphic variant and CAD3,4. However, these outcomes have not been supported by the other studies5. In present study, the frequencies of D/D genotype and D allel of ACE gene considerably higher in children with parental history of premature CAD than control group. We showed that the frequencies of the DD genotype and the D allel of ACE I/D gene polymorphism are higher in children with parental history of premature CAD. This results may be associated with an increased risk for development of atherosclerosis. It may be contribute to the detection of the risk of children with a parental history of CAD. Thus, further large population studies must be done to confirm this results. The study protocol was approved by the Local Ethical Committee of Celal Bayar University, and informed written consent was obtained from all participants. This study was funded by Celal Bayar University.

Arterial stiffness of peripheral vasculature in patients with chronic obstructive pulmonary disease and its association with arterial hypertension

Aim. To study the structural and functional state of vascular wall, arterial stiffness of large peripheral arteries (common carotid arteries, renal arteries) in patients with severe chronic obstructive pulmonary disease and its association with arterial hypertension. Methods. The study included 67 patients of working age, mainly males, having chronic obstructive pulmonary disease. Among them, 52 patients had severe chronic obstructive pulmonary disease (defined by GOLD III, 2011), 15 had concomitant arterial hypertension of I and II stage. Structural and functional status of common carotid arteries, renal arteries was assessed by measurement of intima-media thickness, arterial stiffness indexes were calculated. Arterial elasticity indices: arterial compliance, elastic index, Young’s elastic modulus were calculated based on the results of ultrasonography of main arterial wall parameters (diameter, arterial wall thickness) and blood pressure measurement. Results. A decrease in common carotid arteries and renal arteries wall elasticity was revealed in patients with chronic obstructive pulmonary disease. Increase of stiffness index in patients with severe chronic obstructive pulmonary disease associated with arterial hypertension, marking the decreased arterial wall elasticity, was registered both in common carotid arteries and renal arteries. Conclusion. In common carotid arteries vascular wall thickness contribute the most in vascular wall stiffness increase, compared to altered hemodynamics in renal arteries. Development of arterial hypertension in these patients is a predicting factor for further large vessel remodeling associated with hypoxia.

ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

Abstract Background Chronic treatment with fetal bovine serum (FBS) causes gradual vasoconstriction, vascular wall thickening, and contractility reduction in organ-cultured vascular tissues. We have previously demonstrated that Rho-associated kinase (ROCK) inhibitors prevent the functional alterations of small arteries in response to the FBS treatment. Here, we tested a further hypothesis that the chronic inhibition of ROCK has a protective effect on FBS-induced structural alterations. Methods To verify the new hypothesis, the rabbit mesenteric arterial rings were cultured in FBS-supplemented culture medium with or without Y-27632, a reversible ROCK inhibitor and then western blot, immunohistochemistry, apoptosis assay, and electron microscopy were performed using organ-cultured arterial rings. Results Chronic treatment with Y-27632 maintained the arterial diameter by preventing FBS-induced gradual arterial constriction during organ culture. Y-27632 also reduced the apoptosis and the loss of contractile myosin and actin filaments of smooth muscle cells. In addition, Y-27632 protected the morphological integrity between the endothelial cell layer and smooth muscle cell layer by preventing endothelial cell detachment and platelet endothelial cell adhesion molecule (PECAM) expression decrement. Conclusions Chronic ROCK inhibition provides protective effects against FBS-stimulated structural in addition to functional alterations of vascular smooth muscle cells and endothelial cells. These results strongly suggest that the RhoA/ROCK signaling is crucial for maintaining the structural and functional phenotypes of vasculature, and hence, chronic ROCK inhibition may provide protective effects on excessive growth factor-related vascular diseases including hypertension and atherosclerosis.

Aquaporin-4 antibody-positive myelitis initially biopsied for suspected spinal cord tumors: Diagnostic considerations

Two patients with longitudinally extensive myelopathy were initially biopsied for suspected spinal cord tumors. Both patients were later diagnosed with neuromyelitis optica spectrum disorders (NMOSD) supported by their AQP4-seropositivity. Pathological review of both biopsies revealed demyelinated lesions with thickened vessel walls and tissue rarefaction. Immunohistochemical staining demonstrated findings compatible with acute NMOSD lesions in one case while the other case exhibited findings consistent with chronic NMOSD lesions. A pre-biopsy differential diagnosis of longitudinally extensive spinal cord tumors should include NMOSD. Specific biopsy features, such as cystic changes with vascular wall thickening and astrocyte injury, should raise suspicion for NMOSD.

The interaction of transient receptor potential melastatin 7 with macrophages promotes vascular adventitial remodeling in transverse aortic constriction rats

Transient receptor potential melastatin 7 (TRPM7), a novel channel kinase, has been recently identified in the vasculature. However, its regulation and function in vascular diseases remain poorly understood. To address this lack of knowledge, we sought to examine whether TRPM7 can mediate the vascular remodeling process induced by pressure overload in the right common carotid artery proximal to the band (RCCA-B) in male Sprague-Dawley rats with transverse aortic constriction (TAC). The contribution of TRPM7 to amplified vascular remodeling after TAC was tested using morphometric and western blot analyses. Pressure overload-induced vascular wall thickening, especially in the adventitia, was readily detected in RCCA-B. The TRPM7 level was increased with a simultaneous accumulation of macrophages in the adventitia of RCCA-B, whereas the anti-inflammatory molecule annexin-1, a TRPM7 downstream target, was decreased. After the addition of the TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB), significant reductions in macrophage accumulation as well as the expression of monocyte chemotactic protein-1, SM-22-α and collagen I were observed, whereas annexin-1 was rescued. Finally, in cultured vascular adventitial fibroblasts treated with macrophage-conditioned medium, there were marked increases in the expression of TRPM7 and SM-22-α with a concurrent reduction in annexin-1 expression; these effects were largely prevented by treatment with 2-APB and specific anti-TRPM7 small interfering RNA. Our findings provide the first demonstration of the potential regulatory roles of TRPM7 in the vascular inflammation, pressure overload-mediated vascular adventitial collagen accumulation and cell phenotypic transformation in TAC rats. The targeting of TRPM7 has potential therapeutic importance for vascular diseases.

Specific targeting of Egr-1 reduces neointimal lesions and improves RV remodeling in PAH

Purpose: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease with a high mortality and to date no curable treatment. Increased pulmonary blood flow, as in congenital heart disease, is an essential trigger for the development of neointimal lesions that are characteristic for PAH. We recently identified a flow-specific signal, Egr-1, which was activated in both experimental and human PAH. The aim of the present study was to identify the role of Egr-1 in the development of neointimal lesions in experimental PAH. Methods: In wistar rats (n=76), flow-associated PAH was created by combining monocrotaline with an aortocaval (av) shunt. Egr-1 was inhibited via chronic intravenous delivery (every 48h) of catalytic oligodeoxynucleotides (called DNAzymes) specifically targeting Egr-1 in vivo via RNA degradation. Starting at av-shunt, rats were randomized for either DNAzyme therapy (PAH\_DZ), scrambled DNAzymes (PAH\_SCR; scrambled oligonucleotides that do not recognize Egr-1 RNA) or vehicle (PAH_VEH). Sham operated rats served as control (Con). Increased flow was confirmed by echocardiography. At both 1 week and 3 weeks after increased flow animals underwent hemodynamic evaluation and were sacrificed for further histopathological analysis. Results: At 3 weeks PAH rats had increased vascular occlusion (33%±3, vs. 2±0%, p<0.001) and wall thickness (5.6μm±0.7 vs. 0.3±0.0 p<0.001), presence of neointimal lesions (36% vs. 0% of all arterioles), and subsequently increased right ventricular (RV) peak pressure (60mmHg±2 vs. 24±1, p<0.001) and hypertrophy (RV/BW ratio 1.5mg/g±0.1 vs. 0.6±0.1, p<0.001). Treatment with DNAzymes targeting Egr-1 attenuated vascular remodeling as early as 1 week after flow. At 3 weeks DNAzyme treatment significantly reduced vascular occlusion (-47%, p<0.001), wall thickness (-48%, p<0.001) and the development of neointimal lesions (-69%, p<0.001) compared to PAH\_VEH. PAH\_SCR showed no change compared to PAH\_VEH. Moreover, DNAzyme treatment significantly attenuated pulmonary vascular resistance (-27%, p<0.05), RV peak pressure (-12%, p<0.05) and RV hypertrophy (RV/body weight -27%, p<0.05) compared to PAH\_VEH and PAH_SCR. Conclusion: Here we show that RNA specific targeting of Egr-1 attenuates pulmonary vascular remodeling and disease development in a neointimal model of PAH. These data suggest that Egr-1 is an important regulator of PAH development and may possibly form a therapeutic target for future PAH treatment.