Microvascular research最新文献

{"title":"Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities","authors":"Rui Tao ,&nbsp;Zhenyu Wei ,&nbsp;Xiaoxia Chen ,&nbsp;Qian Wang ,&nbsp;Xiuduo Liu ,&nbsp;Qing Lu ,&nbsp;Jie Zhao ,&nbsp;Hui Zhou","doi":"10.1016/j.mvr.2024.104763","DOIUrl":"10.1016/j.mvr.2024.104763","url":null,"abstract":"<div><h3>Aim</h3><div>To reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH).</div></div><div><h3>Methods</h3><div>This study enlisted WMH and age-matched healthy controls (HC). All participants underwent six different tests: magnetic resonance imaging (MRI) of the brain, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), fundus photography, optical coherence tomography (OCT), and visual field testing. Visual field can reflect the function of optic nerve and retina. The peripapillary retinal nerve fiber layer (p-RNFL) was analyzed using OCT. Image J software was employed to measure retinal vascular caliber in fundus photographs and to compute the central retinal artery equivalent (CRAE), central retinal venous equivalent (CRVE) and arteriole-to-venule ratio (AVR).</div></div><div><h3>Results</h3><div>A total of 90 WMH patients and 93 HC participants. In comparison with the HC, the WMH group exhibited reduced cognitive function scores (MoCA: P &lt; 0.001; MMSE: P &lt; 0.001), narrower retinal arteries (P &lt; 0.001), smaller AVR (P &lt; 0.001) and thinner p-RNFL thickness (total: P = 0.026; temporal: P = 0.006). About visual field, both univariate and multivariate analysis showed that mean sensitivity decreased, and mean defect increased in WMH group (P &lt; 0.05). Additionally, correlation analysis indicated a positive correlation between CRAE and AVR with MMSE and MoCA score (r = 0.424–0.57, P &lt; 0.001) and a negative correlation with Fazekas score (CRAE: r = −0.515, P &lt; 0.001; AVR: r = −0.554, P &lt; 0.001), and p-RNFL was negatively correlated with Fazekas score (total p-RNFL: r = −0.192, P = 0.009; temporal p-RNFL: r = −0.217, P = 0.003). Notably, no significant correlation was found between cognitive function and p-RNFL.</div></div><div><h3>Conclusion</h3><div>WMH group exhibit narrower retinal arteries, smaller arteriole-to-venule ratio, damaged p-RNFL and visual function. These alterations in retinal vessels are associate with both neuroimaging and cognitive function. Our results suggest that retinal imaging could serve as a valuable instrument for evaluating WMH and provides some new approaches to study the characteristic markers of WMH.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"158 ","pages":"Article 104763"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of l-glutamine in an ischemic rat heart model","authors":"Akiko Kawakami ,&nbsp;Hiroaki Sato ,&nbsp;Yosuke Nakadate ,&nbsp;Patricia Roque ,&nbsp;Arkady Khoutorsky ,&nbsp;Takashi Matsukawa ,&nbsp;Thomas Schricker","doi":"10.1016/j.mvr.2024.104764","DOIUrl":"10.1016/j.mvr.2024.104764","url":null,"abstract":"<div><h3>Introduction</h3><div><span>l</span>-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied.</div></div><div><h3>Methods</h3><div>This study hypothesized that <span>l</span>-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only. Eighteen male rat hearts were exposed to 15 min of ischemia using the Langendorff system and randomly assigned to three groups of six each. Group one received Krebs-Henseleit (KH) buffer over 20 min before ischemia and during 20 min of reperfusion (Control), group two received KH buffer containing 2.5 mmol･L⁻¹ glutamine during reperfusion (Post-Gln) and group three was given KH buffer containing glutamine before and after the ischemic insult (Pre + Post-Gln). Indicators of hemodynamics such as maximum left ventricular derivative of pressure development (LV dP/dt max) were recorded at 5, 10, 15 and 20 min post-reperfusion. Myocardial levels of O-linked β-<em>N</em>-acetylglucosamine (O-GlcNAc) and heat shock protein 70 (HSP70) were measured by Western blotting technique after 20 min of reperfusion.</div></div><div><h3>Results</h3><div>The LV dp/dt max in the Pre + Post-Gln group was significantly elevated as compared to the Post-Gln group after 10 min of reperfusion and was significantly higher than in the control group at all-time points. Myocardial expression of O-GlcNAc was increased in the Pre + Post-Gln group (<em>P</em> &lt; 0.01 vs. control) without showing any differences in HSP70.</div></div><div><h3>Conclusion</h3><div>In this model of stunned myocardium, pre- and post-ischemic administration of <span>l</span>-glutamine improved cardiac function indicating cardioprotective effects, possibly mediated by O-GlcNAc.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"158 ","pages":"Article 104764"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin-treated RBC dynamics in a microfluidic porous-like network","authors":"Antonios Stathoulopoulos ,&nbsp;Carola S. König ,&nbsp;Sudarshan Ramachandran ,&nbsp;Stavroula Balabani","doi":"10.1016/j.mvr.2024.104765","DOIUrl":"10.1016/j.mvr.2024.104765","url":null,"abstract":"<div><div>The impact of therapeutic interventions on red blood cell (RBC) deformability and microscale transport is investigated, using statins as an exemplar. Human RBCs were treated <em>in vitro</em> with two commonly prescribed statins, atorvastatin and rosuvastatin, at clinically relevant concentrations. Changes in RBC deformability were quantified using a microfluidic-based ektacytometer and expressed in terms of the elongation index. Dilute suspensions of the statin-treated RBCs were then perfused through a microfluidic pillar array, at a constant flow rate and negligible inertia, and imaged. Particle Tracking Velocimetry (PTV) was applied to track RBCs, identify preferential paths and estimate their velocities, whereas image processing was used to estimate cell dynamics, perfusion metrics and distributions. The findings were compared against those of healthy, untreated cells. Statins enhanced RBC deformability in agreement with literature. The extent of enhancement was found to be statin-dependent. The softer statin-treated cells were found to flow in straight, less tortuous paths, spend more time inside the pillar array and exhibit lower velocities compared to healthy RBCs, attributed to their enhanced deformation and longer shape recovery time upon impact with the array posts. The <em>in vitro</em> microfluidic approach demonstrated here may serve as a monitoring tool to personalise and maximise the outcome of a therapeutic treatment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"158 ","pages":"Article 104765"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multimodal imaging approach to investigate retinal oxygen and vascular dynamics, and neural dysfunction in bietti crystalline dystrophy","authors":"Shiyi Yin ,&nbsp;Jinyuan Wang ,&nbsp;Jingyuan Zhu ,&nbsp;Ximeng Feng ,&nbsp;Haihan Zhang ,&nbsp;Haowen Li ,&nbsp;Jingying Xiu ,&nbsp;Chuanqing Zhou ,&nbsp;Qiushi Ren ,&nbsp;Wenbin Wei","doi":"10.1016/j.mvr.2024.104762","DOIUrl":"10.1016/j.mvr.2024.104762","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to explore retinal changes in Bietti crystalline dystrophy (BCD) patients, including retinal metabolism, blood flow, vascular remodeling, and pupillary light reflex (PLR) abnormalities.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 120 eyes from BCD patients and 120 eyes from healthy controls, utilizing a multimodal imaging system (MEFIAS 3200, SYSEYE, Chongqing, China) to evaluate retinal oxygenation, blood flow, vascular structure, and PLR. Measurements included oxygen saturation, blood flow velocity, vessel diameters, and pulsatility metrics. PLR parameters were assessed under specific light stimuli.</div></div><div><h3>Results</h3><div>BCD patients demonstrated significantly higher retinal oxygen saturation and content, but lower oxygen utilization and metabolism compared to controls, with more pronounced declines in those over 40 years old. Vascular parameters revealed smaller external diameters and larger lumen diameters, indicating vascular remodeling. Retinal blood flow was lower, while the resistivity index was higher in BCD patients. Additionally, PLR abnormalities were noted, including reduced constriction amplitude, pupil constriction ratio, constriction duration, and maximum constriction velocity, along with prolonged latency were observed in BCD patients.</div></div><div><h3>Conclusion</h3><div>BCD patients had significant retinal and vascular changes, along with PLR impairments, especially in patients over 40. More targeted interventions should be focused in future research.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104762"},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased angiopoietin-1 improves nailfold capillary morphology in patients with systemic sclerosis","authors":"Yoshihito Shima ,&nbsp;Akane Watanabe ,&nbsp;Nobuto Inoue ,&nbsp;Tetsuya Maruyama ,&nbsp;Eiji Kunitomo ,&nbsp;Yuji Matsushima ,&nbsp;Atsushi Kumanogoh","doi":"10.1016/j.mvr.2024.104761","DOIUrl":"10.1016/j.mvr.2024.104761","url":null,"abstract":"<div><h3>Objective</h3><div>Raynaud's phenomenon is a common symptom of systemic sclerosis. We previously reported that elbow heating increases angiopoietin-1 in the fingertips and alleviates Raynaud's phenomenon. Angiopoietin-1 levels decrease in patients with systemic sclerosis with severe capillary damage. We aimed to conduct a prospective study to confirm whether the increase in angiopoietin-1 caused by heating modifies capillary morphology.</div></div><div><h3>Methods</h3><div>The left ring fingers of 19 patients with systemic sclerosis were monitored six times at 4-week intervals using capillaroscopy, during which both elbows were heated using disposable heating pads for 8 weeks. Blood samples were collected from the same fingertips four times—before heating, twice during heating, and once after heating—to measure angiopoietin-1.</div></div><div><h3>Results</h3><div>In six patients, the peak increase in angiopoietin-1 occurred 4 weeks after the start of heating, whereas in seven patients, the peak value was observed 4 weeks after the termination thereof. No change in the density of the front-row capillaries was observed by capillaroscopy. <u>The proportion of hairpin-shaped capillaries increased from 20.2 % during the preheating period to 26.6 % during the heating period (<em>p</em> = 0.00107).</u> When a correlation coefficient of 0.6 or higher was set as significant, there was a strong correlation between changes in fingertip angiopoietin-1 levels and changes in the proportion of hairpin-shaped capillaries in six patients.</div></div><div><h3>Conclusion</h3><div>Increased angiopoietin-1 levels in the fingertip due to elbow heating may improve the peripheral capillary morphology in patients with systemic sclerosis.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104761"},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the cyclooxygenase-2 pathway in tissue ischemia and revascularization following skeletal muscle injury induced by bothropic snake venom","authors":"Melissa Rodrigues Correia ,&nbsp;Sang Won Han ,&nbsp;Teresa Escalante ,&nbsp;Vanessa Moreira","doi":"10.1016/j.mvr.2024.104760","DOIUrl":"10.1016/j.mvr.2024.104760","url":null,"abstract":"<div><div><em>Bothrops asper</em> venom (Bav) contains metalloproteinases that disrupt the microvascular system, impairing muscle tissue regeneration after injury. This study investigated the impact of the cyclooxygenase-2 (COX-2) pathway on vascular injury and revascularization in muscle injuries induced by Bav. Mice were injected with Bav into the gastrocnemius muscle and treated with lumiracoxib, a selective COX-2 inhibitor, 30 min, 2 days, and 6 days post-Bav injection. Muscle tissue was analyzed at 24 h, 7 days, and 21 days post-injection. A decrease in COX-2 expression at 24 h post-Bav injection indicated significant necrosis and tissue loss. Both Bav injection and lumiracoxib treatment influenced the decrease of prostaglandin (PG)D₂ and PGE₂ production. Seven and 21 days post-Bav injections, COX-2 expression increased, along with PGDs levels unaffected by lumiracoxib, indicating that the other isoform COX-1 pathway could contribute to the release of PGs. Bav/lumiracoxib treated animals presented exacerbated limb ischemia, implying that COX-2-derived prostaglandins preserve vessel integrity. CD31, an angiogenesis marker, initially (24 h) decreased post-Bav injection but increased at 7 and 21 days in Bav/lumiracoxib mice, suggesting a down-modulatory role for COX-2-derived prostaglandins in early angiogenesis and tissue regeneration. Vascular endothelial growth factor (VEGF) production rose 7 days post-Bav injection, supporting its role in angiogenesis. Previous treatment with lumiracoxib promoted release of VEGF levels 21 days post-Bav injury showing that the inhibition of COX-2 pathway in the early stage of revascularization stimulates the neovascularization regulated by elevated release of VEGF. Similarly, metalloproteinases (MMPs), such as MMP-9, MMP-10, and MMP-13, crucial for vascular remodeling, were elevated 21 days after Bav/lumiracoxib treatment. In conclusion, the COX-2 pathway is essential to decrease the high grade of ischemia caused by acute injury induced by Bav. However, the decrease of activity in the COX-2 pathway in the first stages of revascularization contributes to the elevated production of key pro-angiogenic mediators that up-regulate the restoration of microvasculature and blood flow in muscle tissue injured by botropic venoms.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104760"},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels","authors":"Divya Mishra ,&nbsp;Pankaj Yadav ,&nbsp;Hina Iqbal ,&nbsp;Shweta Parashar ,&nbsp;Arvind Singh Negi ,&nbsp;Debabrata Chanda","doi":"10.1016/j.mvr.2024.104758","DOIUrl":"10.1016/j.mvr.2024.104758","url":null,"abstract":"<div><div>Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative <em>ex-vivo</em> vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues. <em>Ex-vivo</em> vasorelaxation potential of DHEA in isolated arterial tissues were evaluated and the mechanism of vasorelaxation induced by DHEA was characterized by contraction experiment in isolated arterial tissue and <em>in-vitro</em> calcium imaging assay using Fluo-4 in primary vascular smooth muscle cells derived from aorta. In the current study, DHEA was found to exhibit potent concentration dependent, endothelium and potassium channel independent vasorelaxation response in conduit and resistance arteries. The block of L-type VDCCs was evident from the findings that DHEA in a concentration-dependent manner inhibited both BAY K-8644 and CaCl₂-induced contractions. The results of the contraction experiment were further substantiated by Fluo-4 mediated calcium imaging assay in primary rat vascular smooth muscle wherein DHEA concentration dependently blocked noradrenaline and BAY K-8644-induced rise in intracellular calcium fluorescence. The present study showed potent endothelium and potassium channel independent vasorelaxation properties of DHEA in aorta, superior and resistance mesenteric artery mediated predominantly through blockade of L-VDCC.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104758"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphometrics of polypoidal choroidal vasculopathy lesions and choroidal vascular associated with treatment response using swept-source optical coherence tomography angiography","authors":"Yue Zhang ,&nbsp;Jianing Wang ,&nbsp;Zhaoxia Zheng ,&nbsp;Shuang Song ,&nbsp;Xiaoya Gu ,&nbsp;Xiaobing Yu","doi":"10.1016/j.mvr.2024.104759","DOIUrl":"10.1016/j.mvr.2024.104759","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and investigate the relationship between imaging biomarkers and treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF).</div></div><div><h3>Methods</h3><div>We retrospectively recruited 56 PCV patients. Choroidal features included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). Quantitative metrics of neovascularization lesions included total vessel length (TVL), average vessel length (AVL), junction density (JD), total number of endpoints (TNE), and mean lacunarity (ML). We performed multivariate logistic and linear regression models to determine the prognostic factors for functional and morphological outcomes.</div></div><div><h3>Results</h3><div>By comparison, functional good-responders had poorer best corrected visual acuity, higher TNE, and lower ML at baseline. Morphological good-responders had higher central retinal thickness, higher TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. High-shrinkage of vessel area subgroup had higher JD and TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. Multivariate analysis showed good morphological response was correlated with lower SFCT (<em>P</em> &lt; 0.01). High-shrinkage subgroup was correlated with lower AVL (<em>P</em> = 0.017) and higher TNE (P &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>Quantitative metrics of neovascularization lesions and choroidal characteristics using SS-OCTA had the potential to be imaging biomarkers for predicting the response to anti-VEGF treatment. PCV lesions with higher TNE and lower AVL tended to appear higher shrinkage of vessel area, and lower SFCT was correlated with good morphological response.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104759"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of microcirculatory endothelial functions in a D-Galactose-induced aging model","authors":"Zhuo Li,&nbsp;Yuhong He,&nbsp;Qiuju Zhang,&nbsp;Bingwei Li,&nbsp;Ruijuan Xiu,&nbsp;Honggang Zhang","doi":"10.1016/j.mvr.2024.104757","DOIUrl":"10.1016/j.mvr.2024.104757","url":null,"abstract":"<div><h3>Background</h3><div>Microcirculation health is critical to human health, and aging is an important factor affecting microcirculation health. Although D-Galactose has been widely used in aging research models, there is a lack of relevant studies on D-Galactose simulating microcirculatory aging. Here, we explored microcirculatory endothelial function in D-Galactose-induced aging mice.</div></div><div><h3>Methods</h3><div>Intraperitoneal injection of 150 mg/(kg·d) of D-Galactose was given to cause senescence in mice. Aging was evaluated by SA-β-gal (senescence-associated β-galactosidase) staining. The auricular skin and hepatic microcirculation of mice were observed and detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and microcirculation apparatus. The aging of microcirculation was analyzed from oxidative stress, endothelial impairment, inflammation, microvascular morphology and hemodynamics.</div></div><div><h3>Results</h3><div>In aging mice, percentage of SA-β-gal positive area, oxidative stress products reactive oxygen species (ROS) and nitric oxide (NO), endothelial impairment marker syndecan-1 (SDC-1), stromal cell derived factor-1 (SDF-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the senescence-associated secretory phenotype (SASP) were all up-regulated. The tortuosity of microvessels increased in aging mice, the linear density did not change significantly, but the total length of narrow microvessels (TLNMV) increased and wide microvessels (TLWMV) decreased, speculate that vasomotor dysfunction may be present. Hemodynamically, both perfusion and velocity of blood flow were reduced in senescent mice, presumably due to endothelial dysfunction.</div></div><div><h3>Conclusion</h3><div>Microcirculatory endothelial dysfunction is induced by D-Galactose, leading to microcirculatory aging. In vivo, this is manifested by elevated levels of oxidative stress, impaired endothelial glycocalyx (eGC), and a greater production of chemokines and adhesive molecules. These changes cause vasomotor dysfunction and remodeling, ultimately leading to hemodynamic impairment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104757"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated treatment with VEGF receptor inhibitors induces phenotypic changes in endothelial cells and pericytes in the rat retina","authors":"Ayuki Nakano,&nbsp;Takaaki Kawada,&nbsp;Akane Morita,&nbsp;Tsutomu Nakahara","doi":"10.1016/j.mvr.2024.104756","DOIUrl":"10.1016/j.mvr.2024.104756","url":null,"abstract":"<div><div>Abnormal ocular angiogenesis is a major cause of visual impairment and vision loss in neovascularization-related diseases. Currently, anti-vascular endothelial growth factor (VEGF) drugs are used to treat ocular neovascularization, but repeated injections are needed to maintain their therapeutic effects. However, repeated injection of anti-VEGF drugs may affect the retinal blood vessel phenotype and diminish therapeutic effects. In this study, we aimed to investigate the phenotypic changes in endothelial cells and pericytes caused by the repeated interruption of the VEGF receptor signaling pathway in neonatal rats. KRN633 (10 mg/kg), a VEGF receptor tyrosine kinase inhibitor, was subcutaneously administered on postnatal day (P)-7 and P8 (first round), P14 and P15 (second round), and P21 and P22 (third round). The rat eyes were collected on P7, P9, P14, P16, P21, P23, P28, and P35. Using retinal flat-mount specimens stained with specific markers for vascular endothelial cells, basement membranes, and pericytes, the arteriolar tortuosity, capillary area density, and distribution of pericytes were evaluated. Significant loss of capillaries was observed the day after the first round of KRN633 treatment, after which aggressive angiogenesis occurred, leading to the formation of tortuous arterioles. Rats that completed second and third rounds of KRN633 treatment showed more severe abnormalities in the retinal vasculature than those that only completed first round treatment. Repeated treatment with KRN633 decreased the anti-angiogenic effects but increased the immunoreactivity of α-smooth muscle actin in the pericytes on veins and capillaries. α-Smooth muscle actin expression was inversely correlated to anti-angiogenic effects. Overall, these results revealed that repeated interruption of VEGF receptor signaling pathway altered the phenotypes of endothelial cells and pericytes and induced anti-VEGF drug resistance. Therefore, careful follow-up is necessary when using anti-VEGF drugs to treat abnormal angiogenesis-associated ocular diseases.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104756"},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}