Microcirculatory and glycocalyx properties are lowered by high salt diet but augmented by western diet in genetically heterogeneous mice

Many individuals in industrialized societies consume a high salt, western diet, however, the effects of this diet on microcirculatory properties and glycocalyx barrier function are unknown. Young genetically heterogeneous male and female mice underwent 12 weeks of normal chow diet (NC), NC diet with 4% salt (NC4%), western diet (WD), or WD with 4% salt (WD4%). Microcirculatory properties and glycocalyx barrier function were evaluated in the mesenteric microcirculation using an intravital microscope equipped with an automated capture and analysis system. Total microvascular density summed across 4-25 μm microvessel segment diameters was lower in NC4% compared to NC and WD (P<0.05). Perfused boundary region (PBR), a marker of glycocalyx barrier function, averaged across 4-25 μm microvessel segment diameters was similar between NC and NC4%, as well as between WD and WD4% (P>0.05). PBR was lower in WD and WD4% compared to NC and NC4% (P<0.05), indicating augmented glycocalyx barrier function in WD and WD4%. There were strong, inverse relationships between PBR and adiposity and blood glucose (r=-0.44 to -0.61, P<0.05). In summary, NC4% induces deleterious effects on microvascular density, whereas WD augments glycocalyx barrier function. Interestingly, the combination of high salt, western diet in WD4% resulted in lower total microvascular density like NC4% and augmented glycocalyx barrier function like WD. These data suggest distinct microcirculatory adaptations to high salt and western diets that coincide when these diets are combined in young genetically heterogeneous male and female mice.

Feline hypertrophic cardiomyopathy: reduced microvascular density and involvement of CD34+ interstitial cells

The sequence of pathological events in feline hypertrophic cardiomyopathy (fHCM) is still largely unknown, although we know that fHCM is characterized by interstitial remodeling in a macrophage-driven pro-inflammatory environment and that myocardial ischemia might contribute to its progression. This study aimed to gain further insights into the structural changes associated with interstitial remodeling in fHCM with special focus on the myocardial microvasculature and the phenotype of the interstitial cells. Twenty-eight hearts (16 hearts with fHCM and 12 without cardiac disease) were evaluated in the current study, with immunohistochemistry, RNA-in situ hybridization, and transmission electron microscopy. Morphometrical evaluations revealed a statistically significant lower microvascular density in fHCM. This was associated with structural alterations in capillaries that go along with a widening of the interstitium due to the accumulation of edema fluid, collagen fibers, and mononuclear cells that also proliferated locally. The interstitial cells were mainly of fibroblastic or vascular phenotype, with a substantial contribution of predominantly resident macrophages. A large proportion expressed CD34 mRNA, which suggests a progenitor cell potential. Our results indicate that microvascular alterations are key events in the pathogenesis of fHCM and that myocardial interstitial cell populations with CD34+ phenotype play a role in the pathogenesis of the disease.

Trihydroxyethyl Rutin Provides Neuroprotection in Rats With Cervical Spinal Cord Hemi-Contusion

Objective: To investigate the neuroprotective effects of trihydroxyethyl rutin in rats with cervical spinal cord hemi-contusion.Methods: Adult male Sprague–Dawley rats were subjected to hemi-contusion at a stroke depth of 1.2 mm, and then intraperitoneally injected with 50 or 100 mg/kg trihydroxyethyl rutin per day for 12 weeks (T50 and T100 groups, respectively). Changes in somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and behavior were continuously monitored. At 12 weeks post-injury, immunohistochemical staining was performed to assess changes in cervical spinal cord microvascular morphology. Magnetic resonance imaging (MRI) scans were performed to examine end-stage injury in the cervical spinal cord, and Eriochrome cyanine-stained slices of spinal cord tissue were evaluated for injury.Results: There were no significant differences in biomechanical parameters among the spinal cord injury, T50 and T100 rat groups. At 3 days-post-injury, there was a significant decrease in grip strength. At 12 weeks post-injury, grip strength recovery was significantly better in the T50 and T100 groups than in the injury group. Compared with the injury group, the total limb placement frequency was significantly higher in the T50 group at 2, 4, 6, 10, and 12 weeks post-injury and in the T100 group at 2, 6, 8, and 10 weeks post-injury. Ipsilateral SEPs and MEPs were dynamic, increasing in latency and decreasing in amplitude in the injury compared with sham group. MRI scanning demonstrated that the coronal, sagittal, and transversal lesion areas were smaller in the T50 and T100 groups than in the injury group. Microvascular density showed a greater reduction in the injury group compared with the T50 and T100 groups. Eriochrome cyanine staining showed that the ipsilateral side, residual parenchyma, and gray matter areas were larger in the T50 and T100 groups than in the injury group.Conclusion: Trihydroxyethyl rutin exhibits robust neuroprotective effects, improving limb motor function and nerve electrophysiological parameters after spinal cord injury, maintaining microvascular density, and reducing the area of injury and degree of demyelination.

Visual Impairments Are Associated With Retinal Microvascular Density in Patients With Parkinson’s Disease

ObjectiveThis study aimed to evaluate retinal microvascular density in patients with Parkinson’s disease (PD) and its correlation with visual impairment.MethodsThis cross-sectional study included 24 eyes of 24 patients with PD and 23 eyes of 23 healthy controls. All participants underwent ophthalmic examination, visual evoked potential (VEP) test, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and optical coherence tomography angiography (OCTA) examination. The correlation between retinal microvascular density and visual parameter was evaluated using Spearman correlation analysis, and the area under receiver operating characteristic curve (AUROC) was calculated.ResultsParkinson’s disease patients had prolonged P100 latency (P = 0.041), worse vision-related quality of life (composite score and 3 of 12 subscales in NEI VFQ-25), and decreased vessel density (VD) in all sectors of 3-mm-diameter region (all P &lt; 0.05) compared with healthy controls. There were no statistical differences in the ganglion cell-inner plexiform layer (GCIPL) thickness and retinal nerve fiber layer (RNFL) thickness between the two groups. A negative correlation was found between P100 latency and nasal and superior sectors of macular VD in a 3-mm-diameter region (r = −0.328, P = 0.030; r = −0.302, and P = 0.047, respectively). Macular VD in a 3-mm-diameter region showed diagnostic capacities to distinguish PD patients from healthy controls (AUROCs, ranging from 0.655 to 0.723).ConclusionThis study demonstrated that decreased retinal microvascular density was correlated with visual impairment in PD patients. Retinal microvasculature change may occur earlier than visual decline and retinal structure change and has the potential to be a promising diagnostic marker for early PD.

Microtubule associated protein 4 (MAP4) phosphorylation reduces cardiac microvascular density through NLRP3-related pyroptosis

Phosphorylation of MAP4 (p-MAP4) causes cardiac remodeling, with the cardiac microvascular endothelium being considered a vital mediator of this process. In the current study, we investigated the mechanism underlying p-MAP4 influences on cardiac microvascular density. We firstly confirmed elevated MAP4 phosphorylation in the myocardium of MAP4 knock-in (KI) mice. When compared with the corresponding control group, we detected the decreased expression of CD31, CD34, VEGFA, VEGFR2, ANG2, and TIE2 in the myocardium of MAP4 KI mice, accompanied by a reduced plasma concentration of VEGF. Moreover, we observed apoptosis and mitochondrial disruption in the cardiac microvascular endothelium of MAP4 KI animals. Consistently, we noted a decreased cardiac microvascular density, measured by CD31 and lectin staining, in MAP4 KI mice. To explore the underlying mechanism, we targeted the NLRP3-related pyroptosis and found increased expression of the corresponding proteins, including NLRP3, ASC, mature IL-1β, IL-18, and GSDMD-N in the myocardium of MAP4 KI mice. Furthermore, we utilized a MAP4 (Glu) adenovirus to mimic cellular p-MAP4. After incubating HUVECs with MAP4 (Glu) adenovirus, the angiogenic ability was inhibited, and NLRP3-related pyroptosis were significantly activated. Moreover, both cytotoxicity and PI signal were upregulated by the MAP4 (Glu) adenovirus. Finally, NLRP3 inflammasome blockage alleviated the inhibited angiogenic ability induced by MAP4 (Glu) adenovirus. These results demonstrated that p-MAP4 reduced cardiac microvascular density by activating NLRP3-related pyroptosis in both young and aged mice. We thus managed to provide clues explaining MAP4 phosphorylation-induced cardiac remodeling and enriched current knowledge regarding the role of MAP4.

The effect of short-term use of finasteride versus cyproterone acetate on perioperative blood loss with monopolar transurethral resection of prostate

Background Perioperative bleeding is the most common complication related to transurethral resection of prostate; the aim of the study was to compare the effect of pre-operative use of finasteride versus cyproterone acetate (CPA) on blood loss with monopolar TURP. Methods This prospective randomized controlled study was conducted on (60) patients with BPH underwent monopolar TURP between July 2019 and July 2020. Patients were distributed into three equal groups; CPA group: 20 patients received cyproterone acetate 50 mg tab BID for two weeks before TURP, finasteride group: 20 patients received single daily dose of finasteride 5 mg for two weeks before TURP, control group: 20 patients received no treatment before TURP, all patients underwent monopolar TURP, and then histopathological examination of the resected tissues was done with assessment of the microvascular density of the prostate. Results Our study showed that there was significant decrease in intraoperative blood loss and operative time in CPA and finasteride groups in comparison with control group (p = 0.0012) (p < 0.0001), respectively, significant decrease in post-operative Hb and HCT value in finasteride and control groups in comparison with CPA group (p < 0.01), significant increase in specimen weight in CPA group compared to other groups (p < 0.01), and there was also significant decrease in microvascular density in CPA group in comparison with other groups (p < 0.01). Conclusion Cyproterone acetate is more effective than finasteride in decreasing perioperative bleeding with TURP by decreasing microvascular density of the prostate.

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

<b><i>Introduction:</i></b> The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. <b><i>Methods:</i></b> PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO₂ and liver parenchymal VEGF were assessed. <b><i>Results:</i></b> Eleven rabbits were included after PVE (R-PVE, <i>n</i> = 5; P-PVE, <i>n</i> = 6). TVD in the nonembo­lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm²; <i>p</i> &#x3c; 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO₂ and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. <b><i>Discussion/Conclusion:</i></b> Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.

Examination of Micro Vascular Density on Metastatic Colorectal Cancer of RAS Mutant-Type as Anti Vegf Therapy Predictor

According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Colon Cancer Version 2.2019, mCRC patients with mutant type RAS were treated with anti-VEGF. However, the use of the targeting therapy still had inconsistent results. Neoangiogenesis studies had been used as a basis to assess the prognosis of mCRC. Microvascular density (MVD) had become the morphological gold standard to assess neovascularization in human tumors. This study proved the existence of low microvascular density (MVD) in mCRC patients with mutant type RAS status as a predictor of failure of anti-VEGF therapy. There were 29 patients at Dr. Soetomo Academic Hospital from 2015-2018 who had their RAS status checked and tested for microvascular density (MVD). The results of this study were analyzed using SPSS 23.0. In the Mutant-type of RAS group, this study examined microvascular density (MVD). 11 (73%) research subjects with high MVD scores and 4 (27%) research subjects had low MVD scores. Besides, 27% microvascular density (MVD) was low, in the mutant-type of RAS mCRC patient which could be a predictor factor for the failure of anti-VEGF therapy.

Chirurgie subkutaner Mastzelltumoren beim Hund: Prognosefaktoren und Outcome

Gill V, Leibman N, Monette S et al. Prognostic Indicators and Clinical Outcome in Dogs with Subcutaneous Mast Cell Tumors. J Am Anim Hosp Assoc 2020; 56 (4): 215–225 Mastzelltumoren (MZT) sind häufige kutane Neoplasien beim Hund, für die verschiedene prognostische Faktoren beschrieben wurden. Zu diesen zählen der histologische Grad nach Patnaik (3 Grade) oder Kiupel (2 Grade) sowie einige Marker zellulärer Differenzierung wie AgNORs (agyrophylic nuclear organizer regions), Ki-67 oder PCNA (proliferating cell nuclear antigen). Weitere prognostisch aussagekräftige Parameter sind der c-Kit-Mutationsstatus, die mikrovaskuläre Dichte (microvascular density, MVD) und der mitotische Index (MI). Ziel der Studie war, den klinischen Verlauf nach operativer Entfernung subkutaner MZT beim Hund auszuwerten und die Wertigkeit der verschiedenen Prognosefaktoren zu validieren.