Assessment Of Vascular Density Research Articles

CT Assessment of Vascular Density at Limbus Area after Excimer Laser Refractive Surgery in Myopic Patients

Purpose: to assess the indicators of vascular network density at limbus area in patients with myopia and myopic astigmatism before and after excimer laser refractive surgery.Material and methods. A total of 22 patients aged 18 to 37 years with myopia and myopic astigmatism of varying degrees, who previously underwent excimer laser refractive surgery, were examined. Additionally, the vascular network density at limbus area was assessed quantitatively in the preoperative and early postoperative periods using the Nidek RS-3000 AngioScan OCT device and utilizing a module for scanning the anterior segment of the eye.Results. One hour after excimer laser refraction surgery, there was a decrease in vascular network density at limbus area in all four analyzed sectors (upper, lower, temporal, nasal). One day after surgery, there was an increase in this indicator, tending to preoperative values. We were unable to identify the dependence of the degree of vascular network density on the method of corneal flap formation.Conclusion. OCT-angiography makes it possible to assess the indicators of vascular density at limbus area. The estimated indicators varied depending on the time passed after excimer laser refractive surgery.

Quantitative assessment of vascular density in diabetic retinopathy subtypes with optical coherence tomography angiography

BackgroundQuantitative assessment of vascular density (VD) of retinal and choriocapillaris (CC) in various stages of diabetic retinopathy (DR) using spectral domain optical coherence tomography angiography (SD OCTA).Methods188 eyes of 97 participants were recruited in this cross-sectional study. The macular OCTA (3x3mm) scan was performed and the computer algorithm assessed VD at the level of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC.ResultsAll measured parameters were decreased in retinal VD at the more extreme stages of DR, with the exception of SCP foveal VD. There was a constant pattern of decrease in VD of CC from normal cases to cases of NDR and NPDR and then a slight increase occurred in the PDR stage but never touching the normal quantities. Age, fasting blood sugar, and years of diabetes mellitus were correlated with reduced VD in different segments. Multivariate linear regression analysis showed that best-corrected visual acuity (BCVA) was positively correlated with parafoveal VD at SCP and VD of foveal area at CC. VD of all subfields of macular area except foveal DCP VD showed reduced levels in diabetic macular edema (DME) patients compared to those without DME.ConclusionsThe findings of the study endorse retina VD changes as a potential biomarker for DR development before retinopathy becomes clinically evident. It seems that parafoveal VD of SCP and foveal VD of CC are good biomarkers to predict VA in the diabetic patients.

Abstract P034: Vasculature Remodeling In Two Models Of Reduced Renal Mass

Remnant kidney models of chronic kidney disease include the 1/3 nephrectomy (1/3Nx), and 5/6 nephrectomy rats. The 1/3Nx remnant kidney spontaneously atrophies with time, and the 5/6Nx hypertrophies. This disparate remodeling must occur with commensurate vascular changes, examination of which may reveal important molecular pathways and mechanisms underlying changes in renal function. The first step toward realizing this, and the aim of this study, was to characterize the renal vasculature from 1/3Nx, 5/6Nx, and sham Nx rats. Methods: The vasculature was examined in rats 10 weeks following surgery. To-date, these renal vasculatures have been quantified by (1) assessment of vascular density by analysis of bisected, renal vascular casts, and (2) renal blood flow doppler ultrasound. Data: Avg±SEM. Results: 1/3Nx remnant kidney atrophied and 5/6Nx hypertrophied (cross-sectional area: sham n=9; 241±7. 5/6Nx, n=9; 247±8. 1/3Nx, n=12; 132±11: mm 2 ). Despite this, kidney height (intact kidney long axis) to width (short axis) ratio was similar between the remnant models (5/6Nx; 0.8±0.04. 1/3Nx; 0.9±0.04). Sham kidney vascular density was significantly greater than that of 1/3Nx remnant kidneys, which exceeded that of 5/6Nx rats. Cortex vascular density was significantly different between all groups (sham; 95±2%. 1/3Nx; 57±9%. 5/6Nx; 25±11%). The statistical mode of the arterial blood flow distribution was not different between the groups, but mode venous flow was (sham; 100±6. 1/3Nx; 118±9. 5/6Nx; 136±8. Relative units.). Homogeneity of flow was quantified by expressing flow-direction boundaries as a percent of flow area. Sham flow was significantly more homogenous (1.8±0.2) than 1/3Nx (3.7±0.5), and 5/6Nx rats (3.9±0.3). Conclusion: These data demonstrate changes in vascular anatomy and function in both remnant kidney models. Interrogation of anatomical changes and molecular pathways may reveal novel treatment approaches.

Assessment of Vascular Density, Myofibroblastic Activity and Cellular Cannibalism in Aggressive versus Non-Aggressive Central Giant Cell Granuloma of the Jaws

Assessment of Vascular Density, Myofibroblastic Activity and Cellular Cannibalism in Aggressive versus Non-Aggressive Central Giant Cell Granuloma of the Jaws

Angiogenic and pleiotropic effects of VEGF165 and HGF combined gene therapy in a rat model of myocardial infarction.

Since development of plasmid gene therapy for therapeutic angiogenesis by J. Isner this approach was an attractive option for ischemic diseases affecting large cohorts of patients. However, first placebo-controlled clinical trials showed its limited efficacy questioning further advance to practice. Thus, combined methods using delivery of several angiogenic factors got into spotlight as a way to improve outcomes. This study provides experimental proof of concept for a combined approach using simultaneous delivery of VEGF165 and HGF genes to alleviate consequences of myocardial infarction (MI). However, recent studies suggested that angiogenic growth factors have pleiotropic effects that may contribute to outcome so we expanded focus of our work to investigate potential mechanisms underlying action of VEGF165, HGF and their combination in MI. Briefly, Wistar rats underwent coronary artery ligation followed by injection of plasmid bearing VEGF165 or HGF or mixture of these. Histological assessment showed decreased size of post-MI fibrosis in both—VEGF165- or HGF-treated animals yet most prominent reduction of collagen deposition was observed in VEGF165+HGF group. Combined delivery group rats were the only to show significant increase of left ventricle (LV) wall thickness. We also found dilatation index improved in HGF or VEGF165+HGF treated animals. These effects were partially supported by our findings of c-kit+ cardiac stem cell number increase in all treated animals compared to negative control. Sporadic Ki-67+ mature cardiomyocytes were found in peri-infarct area throughout study groups with comparable effects of VEGF165, HGF and their combination. Assessment of vascular density in peri-infarct area showed efficacy of both–VEGF165 and HGF while combination of growth factors showed maximum increase of CD31+ capillary density. To our surprise arteriogenic response was limited in HGF-treated animals while VEGF165 showed potent positive influence on a-SMA+ blood vessel density. The latter hinted to evaluate infiltration of monocytes as they are known to modulate arteriogenic response in myocardium. We found that monocyte infiltration was driven by VEGF165 and reduced by HGF resulting in alleviation of VEGF-stimulated monocyte taxis after combined delivery of these 2 factors. Changes of monocyte infiltration were concordant with a-SMA+ arteriole density so we tested influence of VEGF165 or HGF on endothelial cells (EC) that mediate angiogenesis and inflammatory response. In a series of in vitro experiments we found that VEGF165 and HGF regulate production of inflammatory chemokines by human EC. In particular MCP-1 levels changed after treatment by recombinant VEGF, HGF or their combination and were concordant with NF-κB activation and monocyte infiltration in corresponding groups in vivo. We also found that both–VEGF165 and HGF upregulated IL-8 production by EC while their combination showed additive type of response reaching peak values. These changes were HIF-2 dependent and siRNA-mediated knockdown of HIF-2α abolished effects of VEGF165 and HGF on IL-8 production. To conclude, our study supports combined gene therapy by VEGF165 and HGF to treat MI and highlights neglected role of pleiotropic effects of angiogenic growth factors that may define efficacy via regulation of inflammatory response and endothelial function.

The Notch Signaling System Is Involved in the Regulation of Reparative Angiogenesis in the Zone of Stasis.

The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in the treatment group. Controls were given the same amount of solvent. Seven days after the burn, skin samples were evaluated for VEGF and Dll4 gene expressions. Immunohistochemical analysis was used for the assessment of vascular density, endothelial Dll4 expression, and apoptosis count. Histologic grading of tissue damage was performed. Circulating levels of VEGF and Dll4 were determined. VEGF and Dll4 mRNA levels were found to be simultaneously induced after the burn. In the treatment group, a significant increase in the number of vessels was observed. However, gross evaluation documented an expansion of necrosis to the zone of stasis with marked activation of apoptosis. Histologic assessment showed that the resultant vascular overgrowth was accompanied by extensive edema and abundant infiltration of leukocytes. We provide evidence for the involvement of Notch in the regulation of angiogenesis in zone of stasis burns.

Dynamic contrast‐enhanced MR perfusion imaging of head and neck tumors at 3 Tesla

Dynamic contrast-enhanced (DCE) MR perfusion imaging allows assessment of vascular density and integrity of tumors. The purpose of this study was to determine the diagnostic efficacy of time intensity curve analysis on DCE MRI for characterization of head and neck tumors. Twenty patients underwent T1-weighted fast field echo DCE MRI with temporal resolution of 2.6 seconds. In total, 100 dynamic phases covering 20 slices were obtained in 4.5 minutes. Time to peak (TTP), relative maximum enhancement (RME) ratio, and relative washout ratio (RWO) were calculated. Malignant tumors had a significantly lower RME (p = .025) and prolonged TTP with lower RWO than benign lesions. Postradiation changes had a significantly longer TTP (p = .024) and lower RWO (p = .007) than did postradiation recurrent tumors. Receiver operating characteristic (ROC) analysis revealed RWO had highest accuracy (area under the curve [AUC] = 1.0). DCE MR perfusion imaging provides pivotal information regarding microcirculation, potentially improves differentiation of malignant tumor from postradiation changes.

Vascular Density Has Prognostic Value in Merkel Cell Carcinoma

Merkel cell carcinomas are aggressive tumours for which histological prognostic factors need to be established. This study examines the prognostic role of vascular density, based on CD34 immunohistochemical staining in Merkel cell carcinoma. Thirty-six cases of Merkel cell carcinoma were immunohistochemically stained for the endothelial marker CD34. Vascular density was assessed in the tumor and stroma with a Chalkley eyepiece graticule. The scores of vascular density were correlated with other clinical and histological parameters to determine the prognostic significance of tumor vascularity. Increased vascular density was shown to be significantly associated with a worse prognosis (P = 0.005). A 1-unit increase in total vessel score was associated with a 3.9 times increase in the risk of death (95% hazard ratio confidence limits 1.50-10.32). Other factors associated with a worse outcome included tumor size (P = 0.05), the presence of lymphovascular invasion (P = 0.03), and tumor mast cell count (P < 0.002). Increased vascular density is associated with a worse prognosis in Merkel cell carcinomas. Assessment of vascular density may assist in predicting clinical behavior in these tumors and in evaluating the effects of adjuvant therapy.

Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium

Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium. Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001). Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.

Antiangiogenesis for cancer therapy

Antiangiogenesis for cancer therapy

Mechanisms and therapeutic implications of angiogenesis.

Angiogenesis is a key step in tumor growth and metastasis. Many angiogenic factors have been described, including vascular endothelial growth factor, basic fibroblast growth factor, and thymidine phosphorylase. More recently, a number of naturally occurring inhibitors of angiogenesis, including thrombospondin and angiostatin, have also been identified. The control of angiogenesis by inhibitors regulated by suppressor oncogenes or produced by tumors has emerged as an important mechanism. The development of quantitative assessment of vascular density in primary human tumors has produced a new independent marker of prognosis and could be helpful in selecting patients for antiangiogenic therapy. A large number of antiangiogenic agents are in development, however, new ways to assess their antitumor effects will be necessary for the treatment of advanced cancer. Stabilization of disease may occur by inhibiting new vessel growth, and thus, evidence for a decrease in blood supply should be sought by positron emission tomography scanning, magnetic resonance imaging, or other methods. Markers of angiogenesis in urine or blood will prove to be helpful in the monitoring of treatments.