Differences In Microvascular Density Research Articles

Retinal alterations in evaluation of rheumatoid arthritis with chloroquine treatment: a new approach.

To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. 10 healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. The vascular density in RA group in superficial microvascular was significantly lower than that in control group(P<0.001).Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (P<0.001) and deep microvascular(P=0.018) .Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r=0.868, P=0.0048). The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease. This article is protected by copyright. All rights reserved.

Deep optoacoustic localization microangiography of ischemic stroke in mice

Super-resolution optoacoustic imaging of microvascular structures deep in mammalian tissues has so far been impeded by strong absorption from densely-packed red blood cells. Here we devised 5 µm biocompatible dichloromethane-based microdroplets exhibiting several orders of magnitude higher optical absorption than red blood cells at near-infrared wavelengths, thus enabling single-particle detection in vivo. We demonstrate non-invasive three-dimensional microangiography of the mouse brain beyond the acoustic diffraction limit (<20 µm resolution). Blood flow velocity quantification in microvascular networks and light fluence mapping was also accomplished. In mice affected by acute ischemic stroke, the multi-parametric multi-scale observations enabled by super-resolution and spectroscopic optoacoustic imaging revealed significant differences in microvascular density, flow and oxygen saturation in ipsi- and contra-lateral brain hemispheres. Given the sensitivity of optoacoustics to functional, metabolic and molecular events in living tissues, the new approach paves the way for non-invasive microscopic observations with unrivaled resolution, contrast and speed.

MORPHOLOGICAL FEATURES OF TUMOR ANGIOGENESIS IN INVASIVE DUCTAL BREAST CANCER

Personalized treatment of patients with invasive ductal breast cancer is one of the most pressing issues in modern oncology. Today, information on the human genome and molecular markers is used to targeted therapy and optimize treatment strategies. One of the molecular markers is abnormal tumor angiogenesis. PECAM-1, or CD31, may be a marker of this process. The aim of the study was to comprehensively assess the morphological features and clinical significance of different types of tumors microvessels in invasive ductal breast cancer. CD31 expression was assessed by positive vascular endothelial staining. Using antibodies to CD31 (Ab-1, JC70A, Thermo scientific), we investigated 86 cases of invasive ductal breast cancer. In histological specimens stained with antibodies to CD31, the density of microvessels and areas with strong vascularization, the presence of dilated and atypical dilated capillaries in the intratumoral and peritumoral stroma, the presence of structures with local endothelial lining were assessed. The number of dilated and atypical dilated capillaries, as well as structures with partial endothelial lining was estimated by the semi-quantitative method. According to the results of our study, we showed some differences in the severity of vascular density of the tumor in patients with invasive ductal breast cancer. No differences in microvascular density were found depending on the age of the patients, T and N stages. At the same time, higher values of microvascular density in the intratumoral stroma were noted at G3 degree of differentiation, in triple-negative breast cancer and at HER2/neu positive. The most significant from the prognostic point of view were the number of atypical dilated vessels and structures with local endothelial lining, as well as the presence of characteristic porous structures in loose softly fibrous unformed connective tissue of the peritumoral stroma. Angiogenesis, morphology of tumor vessels is important for prognostic value and this marker can be used to predict the course of invasive ductal breast cancer.

Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct.

Simple SummaryThe oviduct provides the ideal conditions for fertilization and early embryonic development. Adequate vascularization is essential for proper oviduct physiological function. In this work on the mare oviduct, differences in the oviductal artery and arterioles and their ramifications in the infundibulum, ampulla and isthmus were examined. Locally, vascularization is modulated by the action of angiogenic factors, mediated by their specific receptors. In the present study, the isthmus presented the largest vascular area and the highest number of vascular structures in the follicular phase. We have also shown that the relative abundance of angiogenic transcripts and proteins, such as fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all portions of the oviduct throughout the estrous cycle. There was an increase in the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus, and of FGF2 and KDR in the isthmus. This was also observed in the isthmus, where the relative abundance of proteins FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (FGF1, FGF2, VEGF) and their receptors—FGFR1, FGFR2, KDR, respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares’ oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest number of vascular structures in the follicular phase. Transcripts (qPCR) and relative protein abundance (Western blot) of angiogenic factors fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all oviduct portions throughout the estrous cycle. Upregulation of the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus and of FGF2 and KDR in the isthmus were noted. Furthermore, in the isthmus, the relative protein abundance of FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its three portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.

Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation

The cerebral cortex has a number of conserved morphological and functional characteristics across brain regions and species. Among them, the laminar differences in microvascular density and mitochondrial cytochrome c oxidase staining suggest potential laminar variability in the baseline O2 metabolism and/or laminar variability in both O2 demand and hemodynamic response. Here, we investigate the laminar profile of stimulus-induced intravascular partial pressure of O2 (pO2) transients to stimulus-induced neuronal activation in fully awake mice using two-photon phosphorescence lifetime microscopy. Our results demonstrate that stimulus-induced changes in intravascular pO2 are conserved across cortical layers I–IV, suggesting a tightly controlled neurovascular response to provide adequate O2 supply across cortical depth. In addition, we observed a larger change in venular O2 saturation (ΔsO2) compared to arterioles, a gradual increase in venular ΔsO2 response towards the cortical surface, and absence of the intravascular “initial dip” previously reported under anesthesia. This study paves the way for quantification of layer-specific cerebral O2 metabolic responses, facilitating investigation of brain energetics in health and disease and informed interpretation of laminar blood oxygen level dependent functional magnetic resonance imaging signals.

209. The microvascular endothelial glycocalyx: impaired barrier function in preeclampsia with small gestational age neonates

Introduction The glycocalyx, the endothelial lining of membrane-bound proteoglycans and glycoproteins, serves as a functional barrier between flowing red blood cells (RBC) and the endothelial cell membrane. Recent studies suggest that damage to the glycocalyx, which can be reflected by deeper radial penetration of RBC into the glycocalyx, contributes to microvascular dysfunction. Hypothesis We hypothesized that women with preeclampsia, especially those who deliver a small-for-gestational age neonate (PE + SGA, birthweight Methods We compared 30 women with a normotensive pregnancy (NP) to 30 women with preeclampsia (PE), matched for gestational age at time of analysis and presence/absence of labor. Using sidestream dark field imaging of the sublingual microcirculation, we measured 1) the accessibility of the RBC into the glycocalyx layer (perfused boundary region, PBR), defined as the difference between median and maximal RBC column widths, and 2) the microvascular density (total length of perfused microvessels/mm2 area). In healthy vessels, PBR is relatively small due to limited penetration of RBC into the glycocalyx. Results We observed no significant group differences in microvascular density (229 ± 75 mm/mm2 PE, 247 ± 88 mm/mm2 NP, P = 0.48) or PBR (2.20 ± 0.22 μm PE, 2.14 ± 0.30 μm NP, P = 0.14). However, the subset of women with PE + SGA (n = 12) evidenced a significant reduction in vascular density (205 ± 67 vs 306 ± 71 mm/mm2, P Discussion The increase in RBC encroachment (PBR) into the microvascular glycocalyx in PE + SGA compared to NP indicates a change in glycocalyx structure which may be associated with a reduced vascular protective function of the glycocalyx, possibly contributing to endothelial and microvascular dysfunction. Funded by NIH-NICHD (P01 HD030367, R21 HD083659), and AHA16SFRN27870000.

The Effects of Normal Aging on Regional Accumulation of Hyaluronan and Chondroitin Sulfate Proteoglycans in the Mouse Brain.

The brain changes in volume and composition with normal aging. Cellular components of the brain are supported by an extracellular matrix (ECM) comprised largely of hyaluronan (HA) and HA-associated members of the lectican family of chondroitin sulfate proteoglycans (CSPGs). We examined regional differences in microvascular density, neuronal and glial markers, and accumulation of HA and CSPGs in mouse brains during normal aging. The cortex, hippocampus, dentate gyrus, and cerebellum of young (4 months), middle-aged (14 months), and aged (24-26 months) brains were analyzed. Microvascular density decreased in cerebral cortex and cerebellum with age. There were no detectable differences in neuronal density. There was an increase in astrocytes in the hippocampus with aging. HA accumulation was higher in aged brain relative to young brain in the cerebral cortex and cerebellum, but not in other regions examined. In contrast, CSPGs did not change with aging in any of the brain regions examined. HA and CSPGs colocalized with a subset of neuronal cell bodies and astrocytes, and at the microvasculature. Differences in accumulation of ECM in the aging brain, in the setting of decreased microvascular density and/or increased glial activation, might contribute to age-related regional differences in vulnerability to injury and ischemia.

Influence of shape and dispersion media of titanium dioxide nanostructures on microvessel network and ossification

Titanium dioxide nanoparticles (TiO2 NPs) production has been used for pigment, food and cosmetic industry and more recently, shaped as belts for treatment of contaminated water, self-cleaning windows and biomedical applications. However, the toxicological data have demonstrated that TiO2 NPs inhalation induce inflammation in in vivo models and in vitro exposure leads to cytotoxicity and DNA damage. Dermal exposure has limited adverse effects and the possible risks for implants used for tissue regeneration is still under research. Then, it has been difficult to establish a straight statement about TiO2 NPs toxicity since route of exposure and shapes of nanoparticles play an important role in the effects. In this study we aimed to investigate the effect of three different types of TiO2 NPs (industrial, food-grade and belts) dispersed in fetal bovine serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene expression and femur ossification using a chick embryo model after an acute exposure of NPs on the day 7 after eggs fertilization. Microvascular density of chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and vehicles induced biological effects per se. NPs dispersed in FBS or SS have slight differences in microvascular density, mainly opposite effect on angiogenesis gene expression and no effects on femur ossification for NPs dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the alterations in ossification induced by FBS used as vehicle.

Circulation: Clinical Summaries.

Circulation: Clinical Summaries.

The Regional Microvascular Density of the Gluteus Medius Tendon Determined by Immunohistochemistry with CD31 Staining: A Cadaveric Study

There are no studies to date about the vascularisation into the gluteus medius tendon. The purpose of this study was to define the microvessel density of the gluteus medius in 3 zones through a special staining with CD31 and to identify regional differences in microvascular density that may have implications for the healing. We obtained 12 complete gluteus medius tendons from cadavers who had been an average age of 30.3 years old (range 18 to 55). All the donors were males with no known history of hip abnormalities.Following a rigorous protocol, each gluteus medius tendon was divided in 3 portions. Each gluteus medius tendon was divided in 3 portions (I: musculotendinous, II: Tendon, III: Tendon-Bone junction). There were regional differences between all anatomic zones in both the transverse section (p<0.001) and the longitudinal section (p = 0.007). Furthermore, a significant difference was found between zones II and I (mean difference -23.45 IC95% -38.77 to -8.13, p<0.001) and between zones II and III (mean difference -26.08 IC95% -41.39 to -10.76, p<0.001) in transverse section. In longitudinal sections, this difference was found as well between zones II and I (mean difference -29.48 IC95% -51.54 to -7.43, p = 0.01), but not between zones II and III (mean difference -10.87 IC95% -32.93 to 11.18, p = 0.67). The microvessel density was significantly lower in the length of the tendon (central portion) compared to the other 2 regions.

Acute Hemodynamic Response and Uremic Toxin Removal in Conventional and Extended Hemodialysis and Hemodiafiltration: A Randomized Crossover Study

Intensive hemodialysis (HD) may have significant benefits. Recently, the role of extended hemodiafiltration (HDF) has gained interest. The aim of this study was to evaluate the acute effects of extended HD and HDF on hemodynamic response and solute removal. Randomized crossover trial. Stable patients with end-stage renal disease undergoing conventional HD. 13 patients randomly completed a single study of 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF (HDF8), with a 2-week interval between study sessions. Between study sessions, patients received routine conventional HD treatments. Acute hemodynamic effects and uremic toxin clearance. Blood pressure and heart rate, pulse wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, were measured. Clearance and removal of uremic toxins also were studied. Long treatments showed more stability of peripheral systolic blood pressure (change during HD4, -21.7±15.6 mm Hg; during HDF4, -23.3±20.8 mm Hg; during HD8, -6.7±15.2 mm Hg [P=0.04 vs. HD4; P=0.08 vs. HDF4]; and during HDF8, -0.5±14.4 mm Hg [P=0.004 vs. HD4; P=0.008 vs. HDF4]). A similar observation was found for peripheral diastolic and central blood pressures. Cardiac output remained more stable in extended sessions (change during HD4, -1.4±1.5 L/min; during HDF4, -1.6±1.0 L/min; during HD8, -0.4±0.9 L/min [P=0.02 vs. HDF4]; and during HDF8, -0.5±0.8 L/min [P=0.06 vs. HD4; P=0.03 vs. HDF4), in line with the decreased relative blood volume slope in long dialysis. No differences in microvascular density were found. Energy transfer rates were comparable (HD4, 13.3±4.7 W; HDF4, 16.2±5.6 W; HD8, 14.2±6.0 W; and HDF8, 14.5±4.3 W). Small-molecule and phosphate removal were superior during long treatments. β2-Microglobulin and fibroblast growth factor 23 (FGF-23) reduction ratios were highest in HDF8. Small sample size, only acute effects were studied. Treatment time, and not modality, was the determinant for the hemodynamic response. HDF significantly improved removal of middle molecules, with superior results in extended HDF.

Bone Marrow Microvascular and Neuropathic Alterations in Patients With Critical Limb Ischemia

The impact of severe cardiovascular disease and critical limb ischemia (CLI) on the bone marrow (BM) is largely unknown. To investigate microvascular and neuropathic changes in BM of patients with CLI. BM biopsies were obtained from patients with CLI (n=33) included in the Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial (NCT00371371) and controls (n=12). We performed immunohistochemistry and histomorphometry of the BM to assess microvascular density and to evaluate pan-neuronal and sympathetic innervation, which is involved in progenitor cell mobilization. Microvascular density was reduced significantly in CLI compared with controls (P=0.01), as was sympathetic (P=0.047) and pan-neuronal innervation (P=0.006). No differences in microvascular density and sympathetic or pan-neuronal innervation were observed between patients with CLI with and without diabetes mellitus. CLI is associated with BM microvascular and neuropathic changes, both in patients with and without diabetes mellitus.

The Effects of Magnetically Labeled Rat Spleen-originated Endothelial Progenitor Cells on Growth of Glioma in Vivo: An Experimental Study

The aim of this study was to investigate the effects of exogenous endothelial progenitor cells (EPCs) on the growth and invasiveness of glioma in vivo to provide an experimental basis for the value and safety of using magnetically labeled EPCs as target vectors to detect early infiltration of glioma. EPCs were collected from the spleens of healthy Sprague-Dawley rats, made EPCs conditioned medium after identification. Four models of Sprague-Dawley rat glioma (60 rats in total) were established as a control and three experimental groups (group A, B, and C). In the control group, orthotopic transplantation of C6 glioma cells was performed. Compared to the control group, EPCs conditioned medium was added in group A and P7228-labeled EPCs were added in group B. In group C, P7228-labeled EPCs were transplanted via the tail vein. Magnetic resonance imaging and perfusion-weighted imaging were performed on several days. Tumor microvascular density and vascular endothelial growth factor expression were determined through immunohistochemistry. In group C, hypointense areas were detected at the periphery of the tumor on the first day after transplantation of EPCs, and more hypointense areas were found inside the tumor over time. Tumor size in all four groups developed significantly with increasing time (P < .01), but there was no marked difference among these groups at the same time (P > .05). No remarkable differences in microvascular density and cells positive for vascular endothelial growth factor were found at the same time among the four groups (P > .05). Both magnetic resonance imaging and immunohistochemical findings confirmed that exogenous EPCs could not affect the biologic behavior of C6 glioma cells in vivo through a paracrine effect or by direct cellular interaction. Therefore, exogenous EPCs could not exert significant promoting effects on glioma growth.

Metastasis in Melanoma Xenografts Is Associated with Tumor Microvascular Density Rather than Extent of Hypoxia

The development of metastases has been shown to be associated with the microvascular density of the primary tumor in some clinical studies and with the extent of hypoxia in others. The aim of this study was to investigate the validity of these apparently inconsistent observations and to reveal possible links between them. Xenografted tumors of nine melanoma cell lines established from patients with diseases differing in aggressiveness were studied. The aggressiveness of the cell lines was assessed by measuring their lung colonization potential, invasiveness, angiogenic potential, and tumorigenicity. Spontaneous metastasis was assessed in untreated mice and mice treated with neutralizing antibody against vascular endothelial growth factor A (VEGF-A) or interleukin 8 (IL-8). Microvascular density was scored in histologic preparations. Hypoxic fractions were measured by using a radiobiologic assay and a pimonidazole-based immunohistochemical assay. The aggressiveness of the melanoma lines reflected the aggressiveness of the donor patients' tumors. The metastatic propensity was associated with the microvascular density but not with the hypoxic fraction. Anti-VEGF-A and anti-IL-8 treatments resulted in decreased microvascular density and reduced incidence of metastases in all lines. Large hypoxic fractions were not a secondary effect of high cellular aggressiveness, whereas the microvascular density was associated with the cellular aggressiveness. The metastatic propensity was governed by the angiogenic potential of the tumor cells. The differences in microvascular density among the lines were most likely a consequence of differences in the constitutive angiogenic potential rather than differences in hypoxia-induced angiogenesis. VEGF-A and IL-8 may be important therapeutic targets for melanoma.

Differences between the pre-menopausal and post-menopausal uterine fibroid vasculature

Objectives : To quantitatively examine differences in microvascular density between fibroid and myometrial tissue from fibroid uteri removed at hysterectomy, both before and after the menopause, and with hormone replacement therapy. Methods : Factor VIII immunostaining of formalin fixed tissues was used to identify blood vessels, and the vessels counted by an investigator blinded to tissue type or menopausal status. Results : The mean myometrial: fibroid MVD ratio was 2.38 higher in the post-menopausal group (95% CI: 0.12, 4.65, p = 0.0474) than in the pre-menopausal group, with the hormone therapy (HT)-using post-menopausal group lying in between. An increase in microvascular density in the myometrium after the menopause was responsible for most of the change in ratios seen between the pre and post-menopausal pairs. There was a trend to increasing myometrial MVD with increasing number of years post-menopause. Conclusions : Myometrial microvascular density increases markedly after the menopause, while fibroid microvascular density does not alter. Thus, the difference between myometrial and fibroid vasculature becomes greater after the menopause. The implications of this for the treatment of fibroids in post-menopausal women is discussed.

Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats

Two endometrial vascular events, increased permeability and endothelial cell proliferation, characterize the early stages of embryo implantation in rats. Vascular endothelial growth factor (VEGF), a heparin-binding homodimeric glycoprotein, is expressed in the uterus at the time of implantation. The aim of this study was to investigate the effects of systemic administration of blocking antibody to VEGF on endometrial vascular permeability and endothelial cell proliferation around the time of embryo implantation in rats. Rats were injected i.p. with 1.0, 0.8 or 0.6 ml of anti-VEGF antibody or control serum on day 3 of pregnancy and Evans blue dye was administered i.v. on day 5 of pregnancy. The number of implantation sites (blue bands along the uterus) was counted and endothelial cell proliferation was identified using double staining immunohistochemistry. The number of blue bands was significantly lower (P < 0.05) after injection of 1.0 ml blocking antibody (1.8 +/- 1.56) compared with that in control rats (11.6 +/- 1.97). The number of blue bands was significantly different among rats injected with 1.0 (1.8 +/- 1.56), 0.8 (6.0 +/- 3.67) or 0.6 (10.7 +/- 0.33) ml anti-VEGF antibody, indicating a concentration effect of anti-VEGF antibody. No significant differences in endothelial cell proliferation at embryo implantation sites were observed after injection with anti-VEGF antibody or control serum. At intersites (uterine zones between the blue bands), injection of 0.6 ml anti-VEGF antibody caused a significant reduction (P < 0.05) in the percentage of vessels with proliferating endothelial cells (7.25 +/- 2.39%), with a non-significant reduction using 1.0 or 0.8 ml anti-VEGF antibody. No significant differences in microvascular density at either embryo implantation sites or intersites were observed between rats injected with anti-VEGF antibody or control serum. In conclusion, VEGF is the main factor responsible for increased endometrial vascular permeability at implantation. It may regulate endometrial endothelial cell proliferation before implantation and at intersites, thus indicating that factors or mechanisms other than VEGF may regulate endothelial cell proliferation at the site of implantation.

Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats.

Two endometrial vascular events, increased permeability and endothelial cell proliferation, characterize the early stages of embryo implantation in rats. Vascular endothelial growth factor (VEGF), a heparin-binding homodimeric glycoprotein, is expressed in the uterus at the time of implantation. The aim of this study was to investigate the effects of systemic administration of blocking antibody to VEGF on endometrial vascular permeability and endothelial cell proliferation around the time of embryo implantation in rats. Rats were injected i.p. with 1.0, 0.8 or 0.6 ml of anti-VEGF antibody or control serum on day 3 of pregnancy and Evans blue dye was administered i.v. on day 5 of pregnancy. The number of implantation sites (blue bands along the uterus) was counted and endothelial cell proliferation was identified using double staining immunohistochemistry. The number of blue bands was significantly lower (P < 0.05) after injection of 1.0 ml blocking antibody (1.8 +/- 1.56) compared with that in control rats (11.6 +/- 1.97). The number of blue bands was significantly different among rats injected with 1.0 (1.8 +/- 1.56), 0.8 (6.0 +/- 3.67) or 0.6 (10.7 +/- 0.33) ml anti-VEGF antibody, indicating a concentration effect of anti-VEGF antibody. No significant differences in endothelial cell proliferation at embryo implantation sites were observed after injection with anti-VEGF antibody or control serum. At intersites (uterine zones between the blue bands), injection of 0.6 ml anti-VEGF antibody caused a significant reduction (P < 0.05) in the percentage of vessels with proliferating endothelial cells (7.25 +/- 2.39%), with a non-significant reduction using 1.0 or 0.8 ml anti-VEGF antibody. No significant differences in microvascular density at either embryo implantation sites or intersites were observed between rats injected with anti-VEGF antibody or control serum. In conclusion, VEGF is the main factor responsible for increased endometrial vascular permeability at implantation. It may regulate endometrial endothelial cell proliferation before implantation and at intersites, thus indicating that factors or mechanisms other than VEGF may regulate endothelial cell proliferation at the site of implantation.

Microvascular Density of the Human Paraventricular Nucleus Decreases with Aging but Not Hypertension

Microvascular density was determined in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of fixed brain tissue from 19 human subjects ranging in age from 30 to 85 years. Eight of these patients had hypertension. No sex- or hypertension-related differences in microvascular density were found in either the SON or PVN. However, capillary density decreased in the PVN with aging. These results indicate a differential pattern of microvascular loss in the human hypothalamus with aging.