Vessel Luminal Area Research Articles

The effect of heart rate variability on the choroidal vascularity of the optical coherence tomography and angiography in central serous chorioretinopathy.

To investigate the correlation between the autonomic nervous system and choroidal vascularity in patients with central serous chorioretinopathy (CSC), using heart rate variability (HRV) analysis, optical coherence tomography (OCT) and OCT angiography (OCTA). We retrospectively analyzed data of 25 patients with unilateral CSC (50 eyes, including the unaffected fellow eyes) and 25 healthy controls. The assessment involved a 5-minute HRV analysis encompassing both frequency and time domains, especially low frequency (LF), high frequency (HF), and LF/HF ratio. In OCT (12 × 9mm) and en-face OCTA (3 × 3mm) scans, we measured parameters including choroidal vascularity index (CVI), choroidal vessel density in the middle and deep layers, and choriocapillaris flow void. Regression analysis was conducted to elucidate the associations between HRV parameters and OCT/OCTA measurements. Normalized LF(LFnorm) and LF/HF ratios were higher in patients with CSC than in healthy controls. LFnorm and the log-transformed ratio of LF to HF [log(LF/HF)] demonstrated a significant and borderline correlation with CVI in the linear regression analysis (P = 0.040, R2 = 0.171, and P = 0.059, R2 = 0.147, respectively). Both CVI and deep choroid vessel density showed a more significant association with LFnorm and log (LF/HF) in the non-linear quadratic regression analysis than in the linear analysis (all, P < 0.04, R2 > 0.25). The frequency-domain parameters of HRV, including LFnorm and log (LF/HF), demonstrated a significant association with indicators reflective of large choroidal vessel luminal area on macular OCT/OCTA scans. This observation implies complicated modulation of choroidal blood flow by the autonomic nervous system in CSC.

IVUS determination of normal left main stem artery size and plaque burden, and correlation with body surface area in an Indian population.

There is a scarcity of data regarding the normal size of the left main stem coronary artery (LMS) in the Indian population; further data are needed to help determine the optimal device size during percutaneous coronary intervention (PCI). The aim of our study was to determine the normal size of the LMS and to calculate the mean plaque burden (PB) in the left main arteries which are angiographically normal or insignificantly diseased, using intravascular ultrasound (IVUS). We hoped to establish a correlation between LMS size and body surface area (BSA). We collected demographic and coronary artery data from 140 patients who underwent IVUS-guided PCI in the left anterior descending and circumflex arteries over a 2-year period from 2019 to 2020, where a pullback sequence of the LMS was available. The reference and luminal vessel diameters, the reference and luminal vessel areas and the mean plaque burden (PB) were obtained. Regression analysis was used to develop a correlation between BSA and LMS diameter. The IVUS-determined mean reference diameter of the LMS was 5.53±0.63 mm and the mean luminal diameter was 4.62±0.65 mm. The mean reference vessel area was 24.79±5.5 mm2 and the luminal vessel area was 17.19±4.89 mm2. The mean PB was found to be 29.21% in patients with an angiographically normal left main and 32.29% in patients with angiographically insignificant left main stenosis. A linear correlation was noted between the left main reference and luminal vessel diameters; the correlation equations derived were 3.57+1.01 BSA and 2.95+0.87 BSA, respectively. The mean reference and luminal diameters of LMS in the Indian population are on par with the size of LMS in other ethnicities. The vessel compensates for up to 40% PB with vessel remodelling. Hence, a PB of 40% is a good landing zone for stent deployment.

Controlling the Phenotype of Tumor-Infiltrating Macrophages via the PHD-HIF Axis Inhibits Tumor Growth in a Mouse Model.

SummaryThe tumor microenvironment (TME) polarizes tumor-infiltrating macrophages toward tumor support. Macrophage-abundant tumors are highly malignant and are the cause of poor prognosis and therapeutic resistance. In this study, we show that the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) inhibits tumor growth of macrophage-abundant tumors and prolongs mouse survival. FG not only normalizes tumor vessels and improves tumor oxygenation but also directly affects macrophages and activates phagocytosis through the PHD-hypoxia-inducible factor (HIF) axis. Remarkably, FG can promote phagocytic ability of the Ly6Clo subset of tumor-infiltrating macrophages, leading to tumor growth inhibition. Moreover, Ly6Cneg macrophages contributed to blood vessel normalization. Using a malignant tumor mouse model, we characterized macrophage function and subsets. Altogether, our findings suggest that the PHD inhibitor can promote the anti-tumor potential of macrophages to improve cancer therapy.

Coronary CT angiography versus intravascular ultrasound for estimation of coronary stenosis and atherosclerotic plaque burden: A meta-analysis

BackgroundNumerous studies have compared coronary CT angiography (CTA) with quantitativecoronary angiography. However, the ability of coronary CTA to identify atherosclerosis and to accurately measure plaque and coronary area and volume measurements as compared with intravascular ultrasound (IVUS) has not been fully defined. ObjectiveWe sought to assess the ability of coronary CTA to quantify coronary and plaque measurements commonly performed with IVUS. MethodsWe searched multiple databases for diagnostic studies that directly compared coronary CTA and IVUS for coronary plaque detection, vessel luminal area, percentage of area stenosis, plaque area, and plaque volume. We used a bivariate mixed-effects binomial regression model to pool test sensitivity and specificity for detection of any coronary plaque. ResultsForty-two studies that evaluated 1360 patients (75% men; mean age, 59 years) were identified. No significant difference was found between coronary CTA and IVUS measurements of vessel lumen cross-sectional area, plaque area, percentage of area stenosis, or plaque volume within the overall cohort and no difference for the measurement of cross-sectional area (n = 5 studies) and plaque volume (n = 8 studies) among a subgroup that used automated or semiautomated measurement techniques. Sensitivity and specificity of coronary CTA to detect any plaque compared with IVUS were 93% and 92%, respectively, with an area under the receiver-operating curve of 0.97. ConclusionsCompared with IVUS, coronary CTA appears to be highly accurate for estimation of luminal area, percentage of area stenosis, plaque volume, and plaque area and for detection of plaque. The use of automated vessel and stenosis measurements appears promising in limited studies to date.

Effects of Topical Copper Tripeptide Complex on Wound Healing in an Irradiated Rat Model

To evaluate clinical and immunohistopathological effects of topical glycyl-histidyl-lysine-copper (GHK-Cu) on in vivo irradiated rat wounds. Animal model. Academic institution. After dorsal irradiation and a 28-day recovery period, 2 × 8 cm cranially based dorsal flaps were created in Sprague-Dawley rats. Twice daily GHK-Cu gel (test) or aquaphilic ointment (control) was applied for 10 days. Animals were euthanized, digital images of flaps were taken, and harvested tissues were immunohistochemically stained for a vascular endothelium marker, caveolin-1, and vascular endothelial growth factor (VEGF). Digital image analysis was used for outcome measures. Unpaired t-tests were used for statistical analyses; significance of P < .01 accounted for multiple comparisons. By digital analysis of clinical images, 13 test and 10 control animals showed mean ischemic areas of 5.0 cm(2) (SD = 0.9) for tests and 3.8 cm(2) (SD = 1.1; P = .011) for controls. Whole slide digitized images allowed quantification of caveolin-1-stained blood vessels and VEGF expression in fibroblasts at the interface of healing flaps. Caveolin-1 analyses showed a mean of 209.0 vessels (SD = 111.1) and a mean vessel luminal area of 525.7 um(2) (SD = 191.0) in tests and 207.4 vessels (SD = 109.4; P = .973) and 422.8 um(2) (SD = 109.7; P = .118) in controls. VEGF quantified as the percentage of pixels exceeding a colorimetric threshold, with higher fractions of positive pixels indicating more intense staining, showed a mean intensity score of 0.34 (SD = 0.19) in tests and 0.54 (SD = 0.41; P = .169) in controls. Irradiated dorsal rat flaps treated with topical GHK-Cu gel demonstrated no difference in flap ischemia, blood vessel number or area, or VEGF expression compared to controls.

Smooth Muscle Specific Deletion of Ndst1 Leads to Decreased Vessel Luminal Area and No Change in Blood Pressure in Conscious Mice

Heparan sulfate proteoglycans are abundant matrix and membrane molecules. Smooth muscle specific deletion of one heparan sulfate biosynthetic enzyme, N-deacetylase-N-sulfotransferase1 leads to decreased vascular smooth muscle cell proliferation, and vascular wall thickness. We hypothesized that this may lead to changes in blood pressure in conscious mice. Blood pressure was measured via telemetry in SM22αCre(+)Ndst1(-/-)(n = 4) and wild type (n = 8) mice. Aorta and thoracodorsal artery luminal area is significantly smaller in SM22αCre(+)Ndst1(-/-) (n = 4-8, P = 0.02, P = 0.0002) compared to wild type (n = 7) mice. Diurnal differences were observed in both cohorts for systolic, diastolic, mean arterial blood pressure, and heart rate (P < 0.001 from T test). No significant differences were found in the above parameters between the cohorts in either light or dark times using a linear mixed model. In conclusion, deletion of N-deacetylase-N-sulfotransferase1 in smooth muscle did not influence any of the blood pressure parameters measured despite significant decrease in aorta and thoracodorsal artery luminal area.

Wall Shear Stress Measurement Using Phase Contrast Magnetic Resonance Imaging with Phase Contrast Magnetic Resonance Angiography in Arteriovenous Polytetrafluoroethylene Grafts

The purpose of the present article was to determine the changes in luminal vessel area, blood flow, and wall shear stress in both the inflow artery and the venous stenosis of arteriovenous polytetrafluoroethylene (PTFE) grafts. Polytetrafluoroethylene grafts were placed from the carotid artery to the ipsilateral jugular vein in 8 castrated juvenile male pigs. Contrast-enhanced magnetic resonance angiography (MRA) with cine phase-contrast magnetic resonance imaging (MRI) was performed 2 weeks after graft placement. The mean wall shear stress at the venous stenosis was 4 times higher than the control vein, while the inflow artery was only 2-fold higher. By day 14, venous stenosis had formed, which was characterized by narrowed area and elevated blood flow. By day 14, there is venous stenosis formation in porcine arteriovenous PTFE grafts with increased shear stress with decreased area when compared to control vein.

FN13762 Murine Breast Cancer: Region-by-Region Correlation of First-Pass Perfusion CT Indexes with Histologic Vascular Parameters

To investigate the correlation between first-pass perfusion computed tomographic (CT) indexes and histologic vascular parameters in FN13762 breast cancer in rats by using region-by-region correlation methods. The Animal Care and Use Committee approved this study. FN13762 murine breast cancer cells were implanted in 14 female Fischer 344 rats, and first-pass perfusion CT was performed. CT perfusion maps depicting blood flow, blood volume, mean transit time (MTT), and permeability-surface area (PSA) product were generated by using commercial perfusion software. The entire tumor area was divided into six separate regions on perfusion maps, and the regional perfusion indexes were quantified. Histologic vascular parameters, including microvessel density (MVD), luminal vessel number, luminal vessel area, and luminal vessel perimeter, were measured in the histologic region corresponding to the perfusion maps. Correlation analysis was performed between regional tumor perfusion indexes and histologic vascular parameters of the corresponding tumor region. Additionally, mean perfusion values of the entire tumor were correlated with histologic vascular parameters of the hot spot within the tumor. Among 14 rats, four were excluded from the analysis, and results were based on a final total of 10 rats. In tumors, blood flow, blood volume, and PSA product were significantly higher and MTT was significantly shorter (P < .05 for all) than these values in normal neck muscles. At region-by-region correlation, regional blood flow (r = 0.476), blood volume (r = 0.348), and MTT (r = -0.506) were significantly correlated with MVD in the corresponding tumor region (P < .01 for all). After adjustment for biologic variability between rats, regional blood flow (r = 0.614), blood volume (r = 0.515), MTT (r = -0.524), and PSA product (r = 0.228) remained significantly correlated with MVD in the corresponding tumor region. Correlation analysis between CT perfusion indexes of the entire tumor and histologic vascular parameters of the hot spot did not show significant correlations (P > .05). Regional blood flow, blood volume, and MTT are significantly correlated with MVD in the corresponding tumor region.

Digoxin may provide protection against vasospasm in subarachnoid haemorrhage

Vasospasm is a significant reason for poor clinical outcome in subarachnoid haemorrhage (SAH). One of the possible causes of vasospasm is attributed to the inhibition of Na(+)/K(+)-ATPase and increased intracellular calcium. Although digoxin, a cardiac glycoside (CG), inhibits the Na(+)/K(+)-ATPase, diverse and contradictory biological actions of CGs have also been reported. This study aimed to investigate the effect of digoxin on an experimental vasospasm after subarachnoid haemorrhage (SAH) in rats. The rats used in the study were divided into normal, saline, SAH, and drug groups. A double-haemorrhage method was applied for the SAH groups. Normal saline or blood samples were injected into the cisterna magna. No surgical procedures were performed on the normal group. For the drug groups, daily digoxin was administered intraperitoneally after saline or blood injections. On days 3 and 7 after injections, the brains and basilar artery sections of all the groups were prepared for light-microscopic examination. The wall thickness and luminal area of the basilar artery were calculated by using medical imaging software. Increased wall thickness and reduced vessel luminal area were conspicuously significant in the SAH groups which did not receive digoxin. In SAH groups after digoxin administration, the vessel wall thickness decreased, and no significant change was found in vessel wall thickness when compared with the normal and saline groups. The vessel luminal area was not reduced in SAH after digoxin administration. These results suggest that digoxin administration in experimental SAH may have a beneficial effect on the protection against vasospasm. If further investigations support our results, the present study may offer a new insight into the treatment of SAH.

In vive MR evaluation of the vessel wall shear stress in the common carotid artery

Objective To apply a non-invasive and feasible method for the quantification of local wall shear stress (WSS) in vivo using magnetic resonance imaging. Methods The fight common carotid artery of a young healthy male volunteer was examined using cine phase-contrast MR sequence. The cross- sectional area, average flow velocity, maximum velocity and flow rate were obtained. Three dimensional paraboloid model was applied to measure WSS value at common carotid artery. Results The mean/peak WSS was (0.75±0.41)N/m2 for the common carotid artery; The mean (range) velocity was (23.4± 12.0) cm/s; The mean (range) luminal vessel area was (32.2±2.9) mm2; The blood flow rate was (7.8±4. 6) ml/s; Conclusion WSS's magnitude, distribution and changes can be determined by MR imaging combining with the three-dimensional paraboloid method. Key words: Magnetic resonance imaging; Carotid arteries

Assessment of wall shear stress in the common carotid artery of healthy subjects using 3.0-tesla magnetic resonance

Wall shear stress (WSS) has been proven to play a critical role in the formation and development of atherosclerotic plaques. Measurement of WSS in vivo is significant for the clinical assessment of atherosclerosis. To assess the magnitude and distribution of local WSS in the common carotid artery (CCA) in vivo using 3.0T magnetic resonance (MR). The common carotid artery of eight healthy volunteers was studied using a cine phase-contrast MR sequence. A three-dimensional paraboloid model was applied to fit the velocity profiles, and the WSS values were calculated. The cross-sectional area, average flow velocity, maximum velocity, and flow rate were also obtained. Mean WSS was 0.850 +/- 0.195 (range 0.132-3.464) N/m(2) for the common carotid arteries; the spatial and temporal distribution and change of WSS were displayed. During a cardiac cycle, the mean velocity was 22.8 +/- 3.5 (16.9-28.3) cm/s, blood flow rate 8.03+/-1.45 (5.73-10.72) ml/s, and luminal vessel area 34.94+/-7.06 (24.25-49.01) mm(2). Local WSS values in CCAs can be measured using 3.0T MR imaging combined with image-processing techniques. Intersubject variations were found in the distribution and magnitude of wall shear stress as well as in the flow profile pattern in CCAs, which may be caused by different vessel morphologies.

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Venous injury and subsequent venous stenosis formation are responsible for hemodialysis graft failure. Our hypothesis is that these pathological changes are in part related to changes in wall shear stress (WSS) that results in the activation of matrix regulatory proteins causing subsequent venous stenosis formation. In the present study, we examined the serial changes in WSS, blood flow, and luminal vessel area that occur subsequent to the placement of a hemodialysis graft in a porcine model of chronic renal insufficiency. We then determined the corresponding histological, morphometric, and kinetic changes of several matrix regulatory proteins including VEGF-A, its receptors, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal vessel area by performing phase-contrast MRI with magnetic resonance angiography in 21 animals at 1 day after graft placement and prior to death on day 3 (n = 7), day 7 (n = 7), and day 14 (n = 7). At all time points, the mean WSS at the vein-to-graft anastomosis was significantly higher than that at the control vein (P < 0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a significant reduction in WSS by day 14 (P < 0.05 compared with day 7) and a decrease in luminal vessel area compared with control vessels. By day 3, there was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7, increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 (P < 0.05) and, by day 14, increased VEGFR-1 and TIMP-1 (P < 0.05) at the vein-to-graft anastomosis compared with control vessels. Over time, the neointima thickened and was composed primarily of alpha-smooth muscle actin-positive cells with increased cellular proliferation. Our data suggest that hemodialysis graft placement leads to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to the development of venous stenosis.

Early and Late Pathogenic Events of Newborn Mice Encephalitis Experimentally Induced by Itacaiunas and Curionópolis Bracorhabdoviruses Infection

In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share many pathological and clinical features present in other rhabdoviruses but distinct virulence and glial targets in newborn albino Swiss mice brain.

Why does menopausal hormone therapy lead to irregular uterine bleeding? Changes to endometrial blood vessels

Abnormal bleeding is common in hormone therapy (HT) users. We aimed to determine how HT alters endometrial blood vessels and stromal factors known to regulate vascular growth and integrity. Prospective observational study of 165 post-menopausal women in Western Australia. The following were measured in endometrial biopsies: vascular density (vessels/mm(2)), total vessel area (total area enclosed by peripheral vascular immunostaining for perivascular pericytes in mm(2)), total luminal area (mm(2)) and vessel wall area (total vessel area minus luminal area), stromal expression of matrix metalloproteinases (MMP) -1, -3, -9 and -14, their tissue inhibitors (TIMPs) -1-4 and vascular endothelial growth factor (VEGF) by immunohistochemistry. Total vessel area was greater during bleeding compared with HT users with no bleeding (P = 0.028) or with a prior irregular bleeding (P = 0.039). Total vessel area was greater in non-HT users compared with HT users with no bleeding (P = 0.021). In HT users, vessel luminal area was greater during bleeding compared with HT users with no bleeding (P = 0.030) and vessel wall area was also increased (P = 0.025). During bleeding there was an increase in stromal TIMP-2 staining (P = 0.044). No significant changes in endometrial MMP or VEGF were seen. Abnormal bleeding in HT users is associated with changes in endometrial vessel size and in stromal expression of factors known to regulate vascular growth and integrity. These changes may contribute to abnormal bleeding.

Assessment of Wall Shear Stress Changes in Arteries and Veins of Arteriovenous Polytetrafluoroethylene Grafts Using Magnetic Resonance Imaging

The purpose of the study was to determine simultaneously the temporal changes in luminal vessel area, blood flow, and wall shear stress (WSS) in both the anastomosed artery (AA) and vein (AV) of arteriovenous polytetrafluoroethylene (PTFE) grafts. PTFE grafts were placed from the iliac artery to the ipsilateral iliac vein in 12 castrated juvenile male pigs. Contrast-enhanced magnetic resonance angiography with cine phase-contrast magnetic resonance imaging was performed. Luminal vessel area, blood flow, and WSS in the aorta, AA, AV, and inferior vena cava were determined at 3 days (D3), 7 days (D7), and 14 days (D14) after graft placement. Elastin von Gieson staining of the AV was performed. The average WSS of the AA was highest at D3 and then decreased by D7 and D14. In contrast, the average WSS and intima-to-media ratio of the AV increased from D3 to D7 and peaked by D14. Similarly, the average area of the AA was highest by D7 and began to approximate the control artery by D14. The average area of the AV had decreased to its lowest by D7. High blood flows through the AA causes a decrease in average WSS and increase in the average luminal vessel area, whereas at the AV, the average WSS and intima-to-media ratio both increase while the average luminal vessel area decreases.

The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials

The inflammatory and fibrous responses in a subcutaneous rat model were evaluated around degradable polyurethane urea (PUUR; Artelon®), with titanium and tissue culture polystyrene (PS) discs having different surface chemical properties but similar surface topography. Cytokines, viability, cellular response, differentiation of cells and fibrous capsule formation and vascularization was investigated after 1, 7 and 21 days of implantation. The exudates retrieved from the pockets were analysed with respect to the total cell numbers, the proportions of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF-α) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of blood vessels, blood vessel luminal area, blood vessel distribution and the fibrous capsule thickness were analysed. The highest number of cells in the exudates around all implants was detected during the early phase of healing (1–7 days). The proportion of ED2-positive cells in the exudates increased from 2–8% at 1 day to 43–56% at 21 days. The levels of TNF-α were low with a decrease at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in particular around PUUR. This study shows that the transition from inflammation to repair (1–21 days) around PUUR, Ti and PS materials was characterized by a decrease in inflammatory cell influx, an increasing proportion of ED2-expressing macrophages, a biphasic TNF-α secretion, an increase of IL-10 and a fibrous capsule formation similar to all materials tested.

In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype: a murine model for studying placental angiogenesis

Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a complex regulator of blood vessel plasticity that plays a pivotal role in both vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A] and vessel regression (in the absence of VEGF-A). Based on the spatial and temporal expression of Ang2 throughout human gestation, we recently suggested that the Ang2 may play a pivotal role in placental angiogenesis. Further, to examine this tenet we have developed a novel murine model system in which in utero Ang2 gene delivery via a non-replicating adenoviral expression vector has the potential to manipulate the blood vessel phenotype in vivo during pregnancy. Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular extracellular matrix, subsequently promoting plasticity of the maternal and fetal vessels, which appear honeycombed due to a 2-fold increase in blood vessel luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading to vascular leakiness with perivascular oedema, which increases placental weight. These observations suggest that the Ang2 overexpression may play a key role in placental vascular remodelling. Furthermore, we suggest a novel new model to study the pathobiology of placental vascularization and the effect of placental blood vessels on fetal phenotype.

Immune mechanism of cardiac remodeling induced by antibodies against to the alpha1-adrenergic receptor

To study the effects of autoantibodies against alpha1-adrenergic receptor on the cardiac remodeling and relevant mechanism. Four-week-old male Wistar rats were immunized with synthesized second extracellular loop of alpha1-adrenergic receptor and raised for one year, with spontaneously hyperetensive rats (SHRs) and no-immunized Wistar rats of the same age as controls. Every one or two months blood was collected from the caudal vein to detect the level of serum antibodies to alpha1-adrenergic receptor by ELISA and the systolic blood pressure (SBP) and heart rate were measured. One year after the rats were killed and their hearts were taken out. The heart weight/body weight ratio, cardiac muscle cell cross-sectional area (CSA), interstitial collagen volume fraction (CVF) and the ratio of perivascular collagen area to vessel luminal area (PVCA) were calculated, the expression of alpha1-adrenergic receptor, c-fos and c-Jun in heart were measured by RT-PCR, Western blotting and immunohistochemistry. During the experiment the blood pressure of the SHRs were significantly higher than those of the immunization group and normal control group (both P < 0.01) without significant difference between the 2 latter groups. The heart weight/body weight ratio, CSA, CVF and PVCA of the immobilization group were 3.32 mg/g +/- 0.25 mg/g, 231 microm(2) +/- 11 microm(2), 5.40% +/- 0.66% and 1.89 +/- 0.62 respectively, all significantly higher than those of the normal control group (3.06 mg/g +/- 0.25 mg/g, 197 microm(2) +/- 19 microm(2), 3.22% +/- 0.15% and 0.86 +/- 0.17 respectively), but still significantly lower than those of the SHR group. Since the second week after immunization, the titre of antibody against of the immunization group began increase, peaked in the second and third months, and then decreased slowly, and remained at a high level by the end of experiment. The titre of antibody was not correlated with blood pressure. Hypertrophy of cardiac muscle cells and increase of sedimentation of collagen in stroma were seen in the hearts of the immunization group. RT-PCR showed that the expression of alpha1D-adrenergic receptor mRNA of the immunization group was 0.55 +/- 0.01, significantly lower than that of the normal control group (0.88 +/- 0.08, P < 0.05); the expression of c-jun mRNA in the immunization group was 0.82 +/- 0.02, significantly higher than that in the normal control group (0.42 +/- 0.07, P < 0.05); and there were no significant differences in the expressions of heart alpha1A- and alpha1B-afrenergic receptors and c-fos mRNAs between these 2 groups. Western blotting showed that the expression of c-jun protein in the immunization group was 6.24 +/- 2.13, significantly higher than that in the normal control group (2.55 +/- 0.58, P < 0.05); and there were no significant differences in the expressions of c-fos andalpha1A-adrenergic receptor proteins between these 2 groups. The antibodies against alpha1-adrenergic receptor up-regulates the expression of c-jun in cardiac muscle cells and interstitial fibroblast, which may be an immunologic mechanism of cardiac remodeling.

Increased peripheral nerve microvessels in early experimental diabetic neuropathy: quantitative studies of nerve and dorsal root ganglia.

Microangiopathy is an important complication of diabetes mellitus and neovascularity is a feature of human diabetic retinopathy. The objective of this work was to evaluate numbers, areas and size distributions of whole nerve, endoneurial and dorsal root ganglia perfused microvessels in a detailed fashion using unfixed tissues from rats with experimental diabetes. Experimental neuropathy was studied in male Sprague-Dawley rats 12 weeks after streptozotocin or citrate buffer injection. Electrophysiological recordings of sciatic-tibial motor and caudal sensory fibers identified conduction slowing in diabetes indicating neuropathy. Diabetics had a rise in the numbers of whole nerve microvessels and endoneurial microvessels with associated rises in vessel densities and total vessel luminal areas. Increased vessel numbers in 15-30 microm diameter size ranges were particularly prominent. There was a rise in summed vascular areas in diabetics but the mean luminal area of vessels was not increased. Similar, but not significant trends were observed in a selective analysis of endoneurial vessels alone. In contrast, dorsal root ganglia microvessels were not increased in number. Early experimental diabetic neuropathy is associated with increased numbers of microvessels supplying the peripheral nerve trunk, likely representing neovascularity.

Automatic accurate non-invasive quantitation of blood flow, cross-sectional vessel area, and wall shear stress by modelling of magnetic resonance velocity data

To apply a new, automatic and non-invasive method for quantification of blood flow, dynamic cross-sectional vessel area, and wall shear stress (WSS) by in vivo magnetic resonance velocity mapping of normal subjects. Prospective, open study. Six young volunteers. A three-dimensional paraboloid model enabling automatic determination of blood flow, vessel distensibility and WSS was applied to blood velocity determinations in the common carotid artery. Blood flow was also determined by a manual edge detection method. Using the new method, the common carotid mean blood flow was 7.28 (5.61-9.63) (mean (range)) ml/s. By the manual-method blood flow was 7.21 (5.55-9.60) ml/s. Mean luminal vessel area was 26% larger in peak systole than in diastole. Mean/peak WSS was 0.82/2.28 N/m2. Manually and automatically determined flows correlated (r2 = 0.998, p < 0.0001). WSS and peak centre velocity were associated (r2 = 0.805, p < 0.0001). Blood flow, luminal vessel area dilatation, and WSS can be determined by the automatic three-dimensional paraboloid method. The hypothesis of association between peak centre velocity and WSS was not contradicted by the results of the present study.