Total Blood Vessel Research Articles

The relationship between total homocysteine levels and small blood vessel disease in patients with white matter changes

The relationship between total homocysteine levels and small blood vessel disease in patients with white matter changes

Hemorrhage risk prediction after computed tomography-guided lung biopsy: Clinical parameters and quantitative pulmonary vascular analysis

Background/purposeWe evaluated the utility of combining quantitative pulmonary vasculature measures with clinical factors for predicting pulmonary hemorrhage after computed tomography (CT)-guided lung biopsy. MethodsPatients who underwent CT-guided lung biopsy were retrospectively included in this study. Clinical and radiographic vasculature variables were evaluated as predictors of pulmonary hemorrhage. The radiographic pulmonary vascular analysis included vessel count, density, diameter, and area, and also blood volume in small vessels with a cross-sectional area ≤5 mm2 (BV5) and total blood vessel volume (TBV) in the lungs. Univariate and multivariate logistic regressions were used to identify the independent risk factors of higher-grade pulmonary hemorrhage and establish the prediction model presented as a nomogram. ResultsThe study included 126 patients; discovery cohort n = 103, and validation cohort n = 23. All pulmonary hemorrhage, higher-grade (grade ≥2) pulmonary hemorrhage, and hemoptysis occurred in 42.9%, 15.9%, and 3.2% of patients who underwent CT-guided lung biopsies. In the discovery cohort, patients with larger lesion depth (p = 0.013), higher vessel density (p = 0.033), and higher BV5 (p = 0.039) were more likely to experience higher-grade hemorrhage. The nomogram prediction model for higher-grade hemorrhage built by the discovery cohort showed similar performance in the validation cohort. ConclusionsHigher-grade pulmonary hemorrhage may occur after CT-guided lung biopsy. Lesion depth, vessel density, and BV5 are independent risk factors for higher-grade pulmonary hemorrhage. Nomograms integrating clinical parameters and radiographic pulmonary vasculature measures offer enhanced capability for assessing hemorrhage risk following CT-guided lung biopsy, thereby facilitating improved patient clinical care.

CT quantification of pulmonary vessels in lung aging

To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging. A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed. The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age. The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function.

Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation

Adding dental pulp stem cells (DPSCs) to vascular endothelial cell–formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-β1), in stabilizing blood vessels in vitro and in vivo. A 3-dimensional coculture spheroid sprouting assay was conducted to compare the functions of E-DPSCs and T-DPSCs in vitro. Dental pulp angiogenesis in the severe combined immunodeficiency (SCID) mouse model was used to explore the roles of E-DPSCs and T-DPSCs in vascularization in vivo. The results demonstrated that both E-DPSCs and T-DPSCs possess smooth muscle cell–like cell properties, exhibiting higher expression of the mural cell–specific markers and the suppression of HUVEC sprouting. E-DPSCs and T-DPSCs inhibited HUVEC sprouting by activating TEK tyrosine kinase (Tie2) signaling, upregulating vascular endothelial (VE)–cadherin, and downregulating vascular endothelial growth factor receptor 2 (VEGFR2). In vivo study revealed more perfused and total blood vessels in the HUVEC + E-DPSC group, HUVEC + T-DPSC group, angiopoietin 1 (Ang1) pretreated group, and vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor pretreated group, compared to HUVEC + DPSC group. In conclusion, these data indicated that E-DPSCs and T-DPSCs could stabilize the newly formed blood vessels and accelerate their perfusion. The critical regulating pathways are Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling.

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Local Adenoviral Delivery of Vascular Endothelial Growth Factor C Induces Lymphangiogenesis in the Conjunctiva in Rabbits

Introduction: The purpose of this study was to determine if conjunctival lymphangiogenesis can be induced using adenoviral delivery of vascular endothelial growth factor C (VEGF-C). Methods: Seventeen New Zealand white rabbits received a subconjunctival injection containing 3.5 × 107 plaque-forming units of an adenoviral vector containing the gene-encoding VEGF-C (Ad-VEGF-C). The contralateral eye was used for control experiment (the same volume of either saline or an empty vector). After 2 weeks, the animals were examined with trypan blue conjunctival lymphangiography, and the eyes were harvested for histology and immunohistochemistry (podoplanin and CD31). Results: Trypan blue conjunctival lymphangiography revealed significantly more extensive conjunctival vessel network in the Ad-VEGF-C group compared with control: 1.35 ± 0.67 versus 0.28 ± 0.17 vessel length/analysed area (p = <0.0001). This finding was confirmed with immunohistochemistry, where a significant increase in the number of lymphatic vessels was found compared to control; 34 ± 9 per mm2 versus 13 ± 8 per mm2 (p = 0.0019). Furthermore, there was a significant increase in lymphatic cross-sectional area; 32,500 ± 7,900 µm2 per mm2 versus 17,600 ± 9,700 µm2 per mm2 (p = 0.0149). Quantification of blood vessels revealed no significant difference in blood vessel density between Ad-VEGF-C and control; 19 ± 9 per mm2 versus 14 ± 8 per mm2 (p = 0.1971). There was no significant difference in total blood vessel area; 13,200 ± 7,600 µm2 per mm2 versus 7,100 ± 3,000 µm2 per mm2 (p = 0.0715). Eyes treated with an adenoviral vector (VEGF-C or empty vector) responded with a reactive cellular response, predominantly lymphocytes, towards the vector. Conclusion: The study demonstrates the feasibility of inducing conjunctival lymphangiogenesis with a single subconjunctival injection of Ad-VEGF-C. Future studies will explore how this can be used with a therapeutic purpose.

Possible involvement of pro-angiogenic activities in the traditional use of the stembark of Oenocarpus bacaba Mart. (Arecaceae) for wound healing in the Republic of Suriname (South America)

Angiogenesis is an important part of the wound healing process. In this study, the aqueous extracts from seven plant species that are used for wound care in the Republic of Suriname (South America), were evaluated at sub-toxic concentrations for their stimulatory effects on the closure of scratch-wounds in cultured human umbilical vein endothelial cells (HUVECs), the formation of capillary-like structures by these cells, and the growth of sub-intestinal blood vessels in developing Tg (fli1a: EGFP) y1/+ zebrafish embryos. Sub-toxic extract concentrations were about one-third of IC50 values in HUVECs which were established using a sulforhodamine B assay after a 3-day exposure period. Data were expressed relatively to those found with untreated controls and considered statistically significantly different from each other when p values &lt; 0.05 (ANOVA). When compared to untreated controls, the Oenocarpus bacaba stembark extract decreased HUVEC scratch-wound areas by about 30%; increased tube length, number of branching points, and number of loops formed by HUVECs by 50-70%, and increased total sub-intestinal blood vessel length in the zebrafish embryos by about 30%. The extracts from Morinda citrifolia (leaf), Luffa acutangula (fruit juice), Momordica charantia (leaf), Psidium guajava (leaf), Cecropia peltata (branch tops), and Spondias mombin (leaf) had no statistically significant effect on any of these variables. These observations suggest that the O. bacaba sample, unlike the other samples, possessed pro-angiogenic properties which may be involved in its beneficial effects in wound healing. Future studies should more elaborately evaluate these plants in order to definitely establish their therapeutic value in wound healing.

Pulmonary arterial pruning is associated with CT-derived bronchiectasis progression in smokers

Loss of small pulmonary arteries measured as the ratio of blood vessel volume in arteries <5 mm2 in cross-section to total arterial blood vessel volume (BV5a/TBVa), with lower values indicating more pruning, was associated with 5-yr progressing CT-derived bronchiectasis in smokers (Odds Ratio (OR) [95% Confidence interval], 1.28 [1.07–1.53] per 5% lower BV5a/TBVa, P = 0.007). Corresponding results in smokers with COPD were: OR 1.45 [1.11–1.89] per 5% lower BV5a/TBVa, P = 0.007. The results support a vascular factor for structural progression of bronchiectasis.

QS16. The Effects of Variations in the Skin Surface Temperature on Capillary Blood Flow Using Video-capillaroscopy

Purpose: Video-capillaroscopy (VC) can be used to evaluate real-time flow of red blood cells in capillaries at a depth of 1-mm from the skin surface. Therefore, this device could be used in microsurgery to assess the perfusion of flaps, replanted fingers, skin grafts, and keloids. The details of capillary changes during skin cooling under VC observations are not known. By investigating the adaptations of capillaries after cooling using VC, we determined the effects of temperature on skin capillaries with those at room temperature, establishing temperature criteria for future VC applications. Therefore, we observed and compared VC findings on skin areas often used for flap harvest at a normal and lower body temperature. Methods: Twenty healthy Japanese adults were included. Skin capillaries were observed at the lateral thigh, forearm, mid-axillary line, abdomen, and fingertip using VC (GOKO Bscan-Z). Ice packs were used to lower the skin temperature to less than 35°C. The VC findings were recorded for three minutes before and after cooling. By means of the ImageJ software, we measured the total blood vessel area (pixels) as a percentage of the total area of the visual field (pixels). Also, we measured the blood flow velocity (μm/s) using GOKO-VIP software and the results for both temperatures (normal and after cooling) were then compared. Results: The average age and BMI were 37.5±9.72 years and 22.4±2.45 kg/m2 respectively. The mean arterial pressure was 89.4±3.1 mmHg. In accordance with the Fitzpatrick phenotype, eleven patients were type II, five were type III, and four were type IV. The average skin temperature before and after cooling were 36.4±0.2°C and 34.7±0.8°, respectively. The blood vessel areas were significantly different before and after cooling in all anatomical areas (p <.001). The average reduction rate of the vessel area after cooling was 63% for the thigh, 30% for the forearm, 43.3% for the mid-axillary line, 35% for the abdomen, and 65% for fingertips. The mean reduction rate of the vessel area was significantly different among anatomic regions (p <.001). The average blood flow velocities were significantly different before and after cooling in all anatomical areas (p <.001). The average blood flow velocity reduction rate after cooling was 75.7% for the thigh, 55.3% for the forearm, 68.9% for the mid-axillary line, 61.6% for the abdomen, and 79.2% for fingertips. The average blood flow velocity reduction rate after cooling was significantly different among anatomic regions (p <.001). Conclusion: Decrease in skin surface temperature resulted in capillary vasoconstriction and a decrease of capillary blood flow velocity in all areas. When VC is used for flap monitoring, it is important to keep the observation area warm since decreasing the temperature in the monitored area might result in the false diagnosis of arterial occlusion.

Automated lung vessel segmentation reveals blood vessel volume redistribution in viral pneumonia

PurposeIt is known from histology studies that lung vessels are affected in viral pneumonia. However, their diagnostic potential as a chest CT imaging parameter has only rarely been exploited. The purpose of this study is to develop a robust method for automated lung vessel segmentation and morphology analysis and apply it to a large chest CT dataset. MethodsIn total, 509 non-enhanced chest CTs (NECTs) and 563 CT pulmonary angiograms (CTPAs) were included. Sub-groups were patients with healthy lungs (group_NORM, n = 634) and those RT-PCR-positive for Influenza A/B (group_INF, n = 159) and SARS-CoV-2 (group_COV, n = 279). A lung vessel segmentation algorithm (LVSA) based on traditional image processing was developed, validated with a point-of-interest approach, and applied to a large clinical dataset. Total blood vessel volume in lung (TBV) and the blood vessel volume percentage (BV%) of three blood vessel size types were calculated and compared between groups: small (BV5%, cross-sectional area < 5 mm2), medium (BV5-10%, 5–10 mm2) and large (BV10%, >10 mm2). ResultsSensitivity of the LVSA was 84.6% (95 %CI: 73.9–95.3) for NECTs and 92.8% (95 %CI: 90.8–94.7) for CTPAs. In viral pneumonia, besides an increased TBV, the main finding was a significantly decreased BV5% in group_COV (n = 14%) and group_INF (n = 15%) compared to group_NORM (n = 18%) [p < 0.001]. At the same time, BV10% was increased (group_COV n = 15% and group_INF n = 14% vs. group_NORM n = 11%; p < 0.001). ConclusionIn COVID-19 and Influenza, the blood vessel volume is redistributed from small to large vessels in the lung. Automated LSVA allows researchers and clinicians to derive imaging parameters for large amounts of CTs. This can enhance the understanding of vascular changes, particularly in infectious lung diseases.

Relationship Between Carotid Artery Angle and Plaque Morphology in Acute Cerebral Infarction Patients.

Background:High-resolution magnetic resonance imaging (HRMRI) can be used to clearly distinguish the luminal structure of the carotid artery (CA); measure the lumen, vessel wall, and total blood vessel area; and accurately describe the morphologic features of plaques.Methods:This study used HRMRI to investigate the relationship between geometric features and volume and composition of carotid atherosclerotic plaques. Patients (n=81) who had experienced acute cerebral infarction (CI) within 7±3 days before admission to the Neurology Department of Beijing Tiantan Hospital between November 2011 and June 2012 were enrolled in the study. CA HRMRI was performed to analyze the geometry and morphology of plaques in 160 blood vessels.Results:The median left and right internal carotid artery angles (ICAAs) were 32.79 and 31.00 degrees, respectively. Aside from the nonplanar external CA angle, plaque volume and angles did not differ significantly between the left and right sides. Age (B=3.77; P=0.03) and nonplanar ICAA (B=4.70; P=0.01) were predictors of left but not right carotid plaque volume. ICAA and bifurcation angle did not predict plaque volume.Conclusions:In this study, CA morphology in acute stroke patients is not associated with plaque volume or composition, but age and nonplanar ICAA can predict left carotid plaque volume.

The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community.

Cardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear. We examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing. We investigated the association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (D LCO) with the primary outcome of peak oxygen uptake (V'O2 ) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peak V'O2 . We found lower FEV1, FVC and D LCO were associated with lower peak V'O2 . For example, a 1 L lower FEV1 and FVC was associated with a 7.1% (95% CI 5.1-9.1%) and 6.0% (95% CI 4.3-7.7%) lower peak V'O2 , respectively. By contrast, FEV1/FVC was not associated with peak V'O2 . Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope, V'O2 at anaerobic threshold (AT), minute ventilation (V'E) at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V'O2 . In a large, community-based cohort of adults, we found lower FEV1, FVC and D LCO were associated with lower exercise capacity, as well as oxygen uptake efficiency slope and ventilatory efficiency. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V'O2 . These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.

Abstract P009: Correlation between immune modulation of macrophage recruitment and new blood vessel formation in a subcutaneous murine mouse model of colorectal cancer

Abstract Purpose: Colorectal cancer is the fourth most common cancer in the United States, accounting for more than 50,000 deaths annually1. The standard treatment is 5-fluorouracil (5-FU)-based chemotherapy, but emerging methods of immunotherapy have gained the attention of investigators and clinicians. A specific cytokine-based strategy for immunotherapy is the blockade of CCL2/MCP-1 (monocyte chemoattractant protein-1)2. CCL2 is a chemotactic cytokine that recruits circulating monocytes to the tumor microenvironment2. These monocytes differentiate into tumor-associated macrophages (TAMs), which promote pro-tumor functions including tumor growth, immunosuppression, and angiogenesis. CCL2 blockade in certain mouse models of cancer has been shown to reduce tumor burden but had not been studied in colorectal cancer. In this study, we examine how cytokine-targeted anti-CCL2 immunotherapy affects tumor-associated macrophage recruitment as well as the promotion of angiogenesis as a standalone and in combination with 5-FU. Methods: Nine-week-old Balb/c mice (n=13) were acclimated for a week in the Small Animal Facility at the University of Arkansas. CT26 cells, a murine colon carcinoma cell line, were cultured in RPMI-1640 media, supplemented with 10% bovine serum, 0.2% amphotericin B/gentamicin, and 1% antibiotic antimycotic solution. 1 × 106 CT26 cells were subcutaneously injected into the left flank of Balb/c mice (10 weeks old). The tumors grew to 75 mm3, upon which Balb/c mice were randomly divided into saline control, immunotherapy, chemotherapy, and combination (immunotherapy + chemotherapy) groups. The immunotherapy and chemotherapy groups were intraperitoneally injected with a 28G insulin syringe with anti-CCL2 and 5-FU at a concentration of 5.0 mg/kg/dose and 15mg/kg/dose, respectively. The control group was injected with an equal volume of sterile saline on days while the combination group received a dose of anti-CCL2 and 5-FU. Tumor-associated macrophages were quantified via immunohistochemistry using anti-CD68 and tumor vasculature was quantified using anti-CD31. Correlation plots were also created to determine a relationship between macrophage recruitment and new blood vessel formation. Results: There was a decrease in the total number of tumor-associated macrophages from Day 3 to 7 (33% decrease) when tumors were treated with anti-CCL2 and 5-FU. The area of vasculature in the combination group showed a slight decrease from Day 3 to Day 7 (29% decrease). There was a slight positive correlation between total macrophage recruitment and new blood vessel formation (R2 = 0.3041). Conclusion: Overall, we have demonstrated that anti-CCL2 in combination with 5-FU has modestly slowed tumor growth, reduced the area of vasculature, and decreased the number of recruited tumor-associated macrophages in a murine model of colorectal cancer. Acknowledgments: This material is based on work supported by the National Institutes of Health (1R15CA202662- 01), National Science Foundation CAREER award (CBET 1751554), and the Arkansas Biosciences Institute. Citation Format: Shelby N. Bess, Timothy J. Muldoon. Correlation between immune modulation of macrophage recruitment and new blood vessel formation in a subcutaneous murine mouse model of colorectal cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P009.

Mechanical loading alleviated the inhibition of β2-adrenergic receptor agonist terbutaline on bone regeneration.

The long-term use of adrenergic medication in treating various conditions, such as asthma, increases the chances of bone fracture. Dynamic mechanical loading at a specific time is a method for improving bone quality and promoting healing. Therefore, we hypothesized that precisely controlling the mechanical environment can contribute to the alleviation of the negative effects of chronic treatment with the common asthma drug terbutaline, which is a β2-adrenergic receptor agonist that facilitates bone homeostasis and defect repair through its anabolic effect on osteogenic cells. Our in vitro results showed that terbutaline can directly inhibit osteogenesis by impairing osteogenic differentiation and mineralization. Chronic treatment in vivo was simulated by administering terbutaline to C57BL/6J mice for 4weeks before bone defect surgery and mechanical loading. We utilized a stabilized tibial defect model, which allowed the application of anabolic mechanical loading. During homeostasis, chronic terbutaline treatment reduced the bone formation rate, the fracture toughness of long bones, and the concentrations of bone formation markers in the sera. During defect repair, terbutaline decreased the bone volume, type H vessel, and total blood vessel volume. Terbutaline treatment reduced the number of osteogenic cells. Periostin, which was secreted mainly by Prrx1+ osteoprogenitors and F4/80+ macrophages, was inhibited by treating the bone defect with terbutaline. Interestingly, controlled mechanical loading facilitated the recovery of bone volume and periostin expression and the number of osteogenic cells within the defect. In conclusion, mechanical loading can rescue negative effects on new bone accrual and repair induced by chronic terbutaline treatment.

Antiangiogenic Effect of Ficus Carica Linn Leaf Extract on Total Blood Vessels, Matrix Metalloproteinase-9 Expression and Macrophages in the Chick Embryo Chorioallantoic Membrane

Background and Aim: Inhibiting angiogenesis is suppose to be more effective in preventing potential cell metastases. Antiangiogenic substances inhibit the supply of nutrients and oxygen to cancer cells so that the development of protooncogens can be inhibited. This study aimed to evaluate the effect of Ficus carica Linn leaf extract as antiangiogenic on total blood vessels, matrix metalloproteinase-9 (MMP-9) expression and total macrophages on chorioalantoic membranes of chicken embryos. Materials and Methods: A total of 25 chicken embryos were randomly assigned to 5 treatment groups, i.e. (C-) induced by Tris-HCl and 2% DMSO solvent; (C +) induced 60 ng of bFGF and Tris-HCl solvent; (T1) induced 60 ng of bFGF and 20 µg of celecoxib; (T2) induced 90 ng of bFGF and 90 µg of F. carica L. extract in 2% DMSO; (T3) was induced by 60 ng of bFGF and 110 µg of F. carica L. leaf extract in 2% DMSO. The total blood vessels observed macroscopically were counted on the main blood vessel branches around the paper disc. Total macrophages were observed on HE staining and MMP-9 expression on IHC staining. Data were analyzed by ANOVA test followed by Tukey's test (p

Quantitative assessment of retinal and choroidal blood vessels volume using a voxel processing of optical coherence tomography angiography images

Recently, we have proposed a voxel processing algorithm of optical coherence tomography angiography (OCTA) images to increase the accuracy of quantitative assessment of retinal and choroidal blood vessels volume. The purpose of this is to ascertain the effectiveness of the algorithm and to use it for determining the volumetric flow index ratio of the vascular network in the choroid (VChor) and the total vascular network (VAll) across the retinal and choroidal layers. Five patients (seven eyes) aged 25 to 68 years without ophthalmic pathologies and nine patients (12 eyes) aged 64 to 79 years with stage II of primary open angle glaucoma (POAG) were given diagnostic OCTA tests (Spectralis OCT2, Heidelberg Engineering, Germany), each consisting of 512 sagittal scans of the peripapillary area. Testing the feasibility of the method showed that the difference between the values of VChor / VAll ratio in two successive OCTA tests of the same patient’ eye does not exceed 5%, whereas the difference is significant between subjects without eye pathologies and patients with POAG (p < 0.05 according to Mann Whitney U test). The voxel processing algorithm proved useful in quantitative assessment of the volumetric flow index of retinal and choroidal blood vessels and in the estimation of the VChor / VAll—the share of choroidal blood vessels volume in the total blood vessels volume within the peripapillary “retina-choroid” layers.

Expression and function of FGF9 in the hypertrophied ligamentum flavum of lumbar spinal stenosis patients

BACKGROUND CONTEXTLigamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF. PURPOSETo evaluate FGF9 expression and function in human LF with and without hypertrophy. STUDY DESIGNThis study employed a basic research study design utilizing human LF tissue for histological analyses. PATIENT SAMPLESHypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery. METHODSLF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF. RESULTSHistological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients’ age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells. CONCLUSIONThe present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration. CLINICAL SIGNIFICANCEThe results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.

Angiogenesis in mammary Paget disease: histopathological analyses of blood vessel density and angiogenic factors

BackgroundWe examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging. The relationships among blood vessel density (BVD), histopathological parameters of blood flow in the nipple, and the expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were examined.MethodsWe calculated the average CD34-positive BVD and podoplanin (D2–40)-positive lymphatic vessel density (LVD) and the proportion of proliferating of endothelial cells in 14 Paget disease, 3 dermatitis biopsy, and 14 age-matched control cases. As a parameter related to blood flow in the nipple, the total CD34-positive blood vessel lumen area relative to the entire nipple area was measured in each Paget disease and control case using an automated image analysis system. Immunohistochemical expression of bFGF and VEGFA in Paget cells was also examined.ResultsThe average BVD and LVD were significantly higher in the Paget disease cases than in the dermatitis (p = 0.003) and control (p < 0.001) cases. The proportion of proliferating endothelial cells was also increased in the Paget disease cases. The ratio of the CD34-positive blood vessel lumen area to nipple area was also significantly higher in the Paget disease than control cases (p = 0.003). The average BVD was correlated with the average LVD (r = 0.734, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.692, p < 0.001). Immunohistochemical expression of bFGF was strong in all Paget disease cases, with a significantly higher expression score in the Paget disease than dermatitis (p = 0.003) and control (p < 0.001) cases. The bFGF, but not VEGFA, expression score, was strongly correlated with the average BVD (r = 0.818, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.503, p = 0.006).ConclusionThese results provide direct histopathological evidence of a marked increase in nipple blood flow in Paget disease detected by clinical imaging. bFGF is considered to play a pivotal role in angiogenesis in mammary Paget disease.

DISTAL PARENCHYMAL VASCULAR VOLUME LOSS IN CLINICAL CT IMAGING AS A PREDICTOR OF LONG-TERM OXYGEN REQUIREMENT AFTER SUBMASSIVE PULMONARY EMBOLISM

SESSION TITLE: Assessment and Outcomes in Pulmonary Thromboembolism SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: Acute pulmonary embolism is a major cause of morbidity and mortality and affects an estimated 300,000–600,000 individuals in the U.S. each year. A subset of patients in pulmonary embolism require oxygen at discharge. In this study we sought to examine the relationship between the distal parenchymal vascular volume loss as measured by computed tomography based 3-D vascular reconstruction and its relationship to home oxygen requirement after submassive pulmonary embolism. METHODS: Upon receiving IRB approval, medical records at Brigham and Women’s hospital were retrospectively searched using the RPDR system for the diagnosis of as well as the presence of terms, “RV dysfunction”, “RV Strain”, or “RV Hypokinesis” on either echo or CT report for a period spanning between 2009 and 2017 in patients diagnosed with pulmonary embolism. Subjects with available CT angiography obtained at the time of diagnosis with quality appropriate for reconstruction were selected for analysis. 3D vascular reconstruction was performed using the Chest Imaging Platform (https://chestimagingplatform.org) and visually inspected for quality and subsequently used to calculate the total blood vessel volume (TBV). Volumes of intraparenchymal blood vessels were computed for vessels with <5mm2 of cross sectional area (BV5) and normalized by the total lung volume (BV5/TBV). Discharge summaries for all patients were searched for key term “home oxygen”. Data is described as median ± IQR. Mann Whitney U test was used to compare the two groups, and a Logistical Regression model was used to build a model predictive of oxygen requirement. RESULTS: Of 46 patients identified as requiring home oxygen on discharge, 25 were excluded due to: chronic home oxygen requirement secondary to COPD, or parenchymal lung disease contributing to their hypoxia. This led to 703 patients divided into patients requiring home oxygen at discharge (n = 21), and patients not requiring home oxygen at discharge (n=682). Mann Whitney U test showed that there was a statistically significant difference between BV5/TBV for patients requiring home oxygen at discharge and patients not requiring home oxygen at discharge (0.31±0.16 vs 0.39 ± 0.19 p = 0.001). In a Logistic Regression Model adjusted for presence of RV dysfunction by echocardiogram or biomarkers (BNP and troponins), BV5/TBV was a statistically significant predictor of the requirement for home oxygen post discharge (p = 0.002). CONCLUSIONS: Distal Parenchymal Vascular Volume Loss is associated with chronic hypoxia requiring home oxygen on discharge after Submassive Pulmonary Embolism. CLINICAL IMPLICATIONS: The study of vascular perfusion may help the understanding of the nature of hypoxemia in pulmonary embolism. DISCLOSURES: No relevant relationships by Samuel Ash, source=Web Response No relevant relationships by German Gonzalez Serrano, source=Web Response No relevant relationships by Syed Moin Hassan, source=Web Response No relevant relationships by Andetta Hunsaker, source=Admin input No relevant relationships by Jasleen Minhas, source=Web Response No relevant relationships by Pietro Nardelli, source=Web Response My spouse/partner as a Employee relationship with BSC Please note: >$100000 Added 03/13/2019 by Gregory Piazza, source=Web Response, value=Salary research relationship with BMS Please note: $5001 - $20000 Added 03/13/2019 by Gregory Piazza, source=Web Response, value=Grant/Research Support research relationship with Janssen Please note: $5001 - $20000 Added 03/13/2019 by Gregory Piazza, source=Web Response, value=Grant/Research Support research relationship with BTG Please note: $5001 - $20000 Added 03/13/2019 by Gregory Piazza, source=Web Response, value=Grant/Research Support research relationship with Portola Please note: $5001 - $20000 Added 03/13/2019 by Gregory Piazza, source=Web Response, value=Grant/Research Support no disclosure on file for Farbod Rahaghi; no disclosure on file for James Chapman Ross; no disclosure on file for Raul San Jose Estepar; No relevant relationships by Ruben San Jose Estepar, source=Web Response no disclosure on file for George Washko