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1.
Biomed Pharmacother ; 151: 113165, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35609370

RESUMO

OBJECTIVE: To investigate the efficacy of a paeoniflorin-sodium alginate (SA)-gelatin skin scaffold for treating diabetic wound in a rat model. METHODS: Bioinks were prepared using various percentages of paeoniflorin in the total weight of a solution containing SA and gelatin. Skin scaffolds containing 0%, 1%, 3%, 5%, and 10% paeoniflorin were printed using 3D bioprinting technology, and scaffold microstructure was observed with scanning electron microscopy. Skin scaffolds were then used in rats with diabetic wounds. H&E staining, Masson staining, and immunohistochemical staining for IL-1ß and CD31 were performed on days 7 and 14. RESULTS: All skin scaffolds had a mesh-like structure with uniform pore distribution. Wounds healed well in each group, with the 1% and 3% groups demonstrating the most complete healing. H&E staining showed that skin accessory organs had appeared in each group. On day 7, collagen deposition in the 3% group was higher than in the other groups (P<0.05), and IL-1ß infiltration was lower in the 10% group than in the 3% group (P = 0.002). On day 14, IL-1ß infiltration was not significantly different between the 10% and 3% groups (P = 0.078). The CD31 level was higher in the 3% group than in the other groups on days 7 and 14 (P<0.05). CONCLUSION: A 3% paeoniflorin-SA-gelatin skin scaffold promoted the healing of diabetic wounds in rats. This scaffold promoted collagen deposition and microvascular regeneration and demonstrated anti-inflammatory properties, suggesting that this scaffold type could be used to treat diabetic wounds.


Assuntos
Alginatos , Complicações do Diabetes , Gelatina , Glucosídeos , Pele , Tecidos Suporte , Alginatos/administração & dosagem , Alginatos/uso terapêutico , Animais , Colágeno/metabolismo , Complicações do Diabetes/complicações , Complicações do Diabetes/terapia , Diabetes Mellitus , Modelos Animais de Doenças , Gelatina/administração & dosagem , Gelatina/uso terapêutico , Glucosídeos/administração & dosagem , Glucosídeos/uso terapêutico , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Monoterpenos/administração & dosagem , Monoterpenos/uso terapêutico , Impressão Tridimensional , Ratos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
2.
Sci Rep ; 12(1): 4304, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277592

RESUMO

Capillary blood vessels, the smallest vessels in the body, form an intricate network with constantly bifurcating, merging and winding vessels. Red blood cells (RBCs) must navigate through such complex microvascular networks in order to maintain tissue perfusion and oxygenation. Normal, healthy RBCs are extremely deformable and able to easily flow through narrow vessels. However, RBC deformability is reduced in many pathological conditions and during blood storage. The influence of reduced cell deformability on microvascular hemodynamics is not well established. Here we use a high-fidelity, 3D computational model of blood flow that retains exact geometric details of physiologically realistic microvascular networks, and deformation of every one of nearly a thousand RBCs flowing through the networks. We predict that reduced RBC deformability alters RBC trafficking with significant and heterogeneous changes in hematocrit. We quantify such changes along with RBC partitioning and lingering at vascular bifurcations, perfusion and vascular resistance, and wall shear stress. We elucidate the cellular-scale mechanisms that cause such changes. We show that such changes arise primarily due to the altered RBC dynamics at vascular bifurcations, as well as cross-stream migration. Less deformable cells tend to linger less at majority of bifurcations increasing the fraction of RBCs entering the higher flow branches. Changes in vascular resistance also seen to be heterogeneous and correlate with hematocrit changes. Furthermore, alteration in RBC dynamics is shown to cause localized changes in wall shear stress within vessels and near vascular bifurcations. Such heterogeneous and focal changes in hemodynamics may be the cause of morphological abnormalities in capillary vessel networks as observed in several diseases.


Assuntos
Deformação Eritrocítica , Eritrócitos , Deformação Eritrocítica/fisiologia , Eritrócitos/fisiologia , Hematócrito , Hemodinâmica , Microvasos/fisiologia
3.
J Acquir Immune Defic Syndr ; 90(2): 170-174, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35135974

RESUMO

BACKGROUND: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy. METHODS: We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders. RESULTS: We found that narrower arteriolar caliber (per 10 µm decrease), wider venular caliber (per 10 µm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/µL (P = 0.006), 33.55 cells/µL (P = 0.01), and 39.09 cells/µL (P = 0.008), accordingly. CONCLUSION: Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Reconstituição Imune , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Microvasos/fisiologia , Estudos Prospectivos , Retina/fisiologia
4.
Biomech Model Mechanobiol ; 21(3): 771-796, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35146594

RESUMO

Red blood cells (RBCs) make up 40-45% of blood and play an important role in oxygen transport. That transport depends on the RBC distribution throughout the body, which is highly heterogeneous. That distribution, in turn, depends on how RBCs are distributed or partitioned at diverging vessel bifurcations where blood flows from one vessel into two. Several studies have used mathematical modeling to consider RBC partitioning at such bifurcations in order to produce useful insights. These studies, however, assume that the vessel wall is a flat impenetrable homogeneous surface. While this is a good first approximation, especially for larger vessels, the vessel wall is typically coated by a flexible, porous endothelial glycocalyx or endothelial surface layer (ESL) that is on the order of 0.5-1 µm thick. To better understand the possible effects of this layer on RBC partitioning, a diverging capillary bifurcation is analyzed using a flexible, two-dimensional model. In addition, the model is also used to investigate RBC deformation and RBC penetration of the ESL region when ESL properties are varied. The RBC is represented using interconnected viscoelastic elements. Stokes flow equations (viscous flow) model the surrounding fluid. The flow in the ESL is modeled using the Brinkman approximation for porous media with a corresponding hydraulic resistivity. The ESL's resistance to compression is modeled using an osmotic pressure difference. One cell passes through the bifurcation at a time, so there are no cell-cell interactions. A range of physiologically relevant hydraulic resistivities and osmotic pressure differences are explored. Decreasing hydraulic resistivity and/or decreasing osmotic pressure differences (ESL resistance to compression) produced four behaviors: (1) RBC partitioning nonuniformity increased slightly; (2) RBC deformation decreased; (3) RBC velocity decreased relative to blood flow velocity; and (4) RBCs penetrated more deeply into the ESL. Decreasing the ESL's resistance to flow and/or compression to pathological levels could lead to more frequent cell adhesion and clotting as well as impaired vascular regulation due to weaker ATP and nitric oxide release. Potential mechanisms that can contribute to these behaviors are also discussed.


Assuntos
Eritrócitos , Microvasos , Velocidade do Fluxo Sanguíneo , Capilares/fisiologia , Eritrócitos/fisiologia , Glicocálix , Microvasos/fisiologia
5.
Int J Mol Sci ; 23(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163192

RESUMO

Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (-) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and ß-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and ß-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and ß-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (-) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, ß-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.


Assuntos
Aloenxertos/metabolismo , Rejeição de Enxerto/imunologia , Interleucina-10/metabolismo , Animais , Células Endoteliais/imunologia , Células Epiteliais/imunologia , Epitélio/imunologia , Sobrevivência de Enxerto/fisiologia , Tolerância Imunológica , Interleucina-10/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microvasos/imunologia , Microvasos/fisiologia , Linfócitos T Reguladores/imunologia , Transplante Homólogo/métodos
6.
Am J Physiol Heart Circ Physiol ; 322(3): H386-H393, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35060753

RESUMO

Acute heat exposure improves microvascular function in aged adults as assessed using reactive hyperemia. The cutaneous and skeletal muscle microcirculations are thought to contribute to this response, but this has never been confirmed due to the methodological challenges associated with differentiating blood flow between these vascular beds. We hypothesized that acute hot water immersion would improve endothelial-dependent, but not endothelial-independent vasodilation in the microcirculation of the vastus lateralis muscle in healthy aged adults. Participants (70 ± 5 yr) were immersed for 60 min in thermoneutral (36°C) or hot (40°C) water. Ninety minutes following immersion, skeletal muscle microdialysis was used to bypass the cutaneous circulation and directly assess endothelial-dependent and endothelial-independent vasodilation by measuring the local hyperemic response to graded infusions of acetylcholine (ACh, 27.5 and 55.0 mM) and sodium nitroprusside (SNP, 21 and 42 mM), respectively. The hyperemic response to 27.5 mM ACh did not differ between thermal conditions (P = 0.9). However, the hyperemic response to 55.0 mM ACh was increased with prior hot water immersion (thermoneutral immersion, 43.9 ± 23.2 mL/min/100 g vs. hot water immersion, 66.5 ± 25.5 mL/min/100 g; P < 0.01). Similarly, the hyperemic response to 21 mM SNP did not differ between thermal conditions (P = 0.3) but was increased following hot water immersion with the infusion of 42 mM SNP (thermoneutral immersion, 48.8 ± 25.6 mL/min/100 g vs. hot water immersion, 90.7 ± 53.5 mL/min/100 g; P < 0.01). These data suggest that acute heat exposure improves microvascular function in skeletal muscle of aged humans.NEW & NOTEWORTHY Acute heat exposure improves microvascular function in aged adults as assessed using reactive hyperemia. The cutaneous and skeletal muscle microcirculations are thought to contribute to this response, but this has never been confirmed due to the methodological challenges associated with differentiating blood flow between these vascular beds. Using the microdialysis technique to bypass the cutaneous circulation, we demonstrated that heat exposure improves endothelial-dependent and endothelial-independent vasodilation in the microcirculation of skeletal muscle in aged humans.


Assuntos
Hipertermia Induzida/métodos , Microcirculação , Músculo Esquelético/irrigação sanguínea , Idoso , Feminino , Humanos , Masculino , Microvasos/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Vasodilatação
7.
Am J Physiol Heart Circ Physiol ; 322(2): H328-H335, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995168

RESUMO

Many individuals in industrialized societies consume a high-salt, Western diet(WD); however, the effects of this diet on microcirculatory properties and glycocalyx barrier function are unknown. Young genetically heterogeneous male and female mice underwent 12 wk of normal chow (NC) diet, 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- to 25-µm microvessel segment diameters was lower in NC4% than in NC and WD (P < 0.05). Perfused boundary region (PBR), a marker of glycocalyx barrier function, averaged across 4- to 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% than in 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.NEW & NOTEWORTHY Many individuals in industrialized societies consume a combination of high-salt and Western diet; however, the effects of this diet on microcirculatory and glycocalyx properties are unknown. This study reveals that a high-salt diet lowers microcirculatory and glycocalyx properties, whereas a Western diet augments glycocalyx barrier function and thickness. Taken together, these data indicate that there are distinct microcirculatory adaptations to high-salt and Western diets that coincide when high-salt and Western diets are combined.


Assuntos
Dieta Ocidental , Glicocálix/metabolismo , Microcirculação , Cloreto de Sódio na Dieta/efeitos adversos , Adiposidade , Animais , Animais não Endogâmicos , Glicemia/metabolismo , Feminino , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiologia , Camundongos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/fisiologia
8.
Br J Pharmacol ; 179(7): 1433-1449, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34766335

RESUMO

BACKGROUND: The microvasculature is a target organ for the early manifestations of cardiovascular disease. Therefore, a better understanding of the prostaglandin system and characterising the effects of mPGES-1 inhibition and concomitant reduction of PGE2 in vascular beds are of interest. EXPERIMENTAL APPROACH: The effects of mPGES-1 inhibition on constriction and relaxation of resistance arteries (diameter: 100-400 µm) from patients with end stage kidney disease (ESKD) and controls (Non-ESKD) were studied using wire-myography in combination with immunological and mass-spectrometry based analyses. KEY RESULTS: Inhibition of mPGES-1 in arteries from ESKD patients and Non-ESKD controls significantly reduced adrenergic vasoconstriction, which was unaffected by the COX-2 inhibitors NS-398 and Etoricoxib, or by the COX-1/COX-2 inhibitor Indomethacin tested in Non-ESKD controls. However, a significant increase of acetylcholine-induced dilatation was observed for mPGES-1 inhibition. In IL-1ß treated arteries, inhibition of mPGES-1 significantly reduced PGE2 levels while PGI2 levels remained unchanged. In contrast, COX-2 inhibition blocked the formation of both prostaglandins. Blockade of PGI2 signalling with an IP receptor antagonist did not restore the reduced adrenergic constriction, neither did blocking PGE2 -EP4 or signalling through PPARγ. A biphasic effect was observed for PGE2 , inducing dilatation at nanomolar and constriction at micromolar concentrations. Immunohistochemistry demonstrated expression of mPGES-1, COX-1, PGIS, weak expression for COX-2, as well as receptor expression for PGE2 (EP1-4), thromboxane (TP) and PGI2 (IP) in ESKD and Non-ESKD. CONCLUSION: Our study demonstrates vasodilating effects following mPGES-1 inhibition in human microvasculature and suggests that several pathways besides shunting to PGI2 are involved.


Assuntos
Artérias , Falência Renal Crônica , Prostaglandina-E Sintases , Adrenérgicos , Artérias/metabolismo , Artérias/fisiologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Etoricoxib , Humanos , Falência Renal Crônica/complicações , Microvasos/metabolismo , Microvasos/fisiologia , Nitrobenzenos , Prostaglandina-E Sintases/antagonistas & inibidores , Prostaglandinas , Sulfonamidas
9.
Am J Physiol Heart Circ Physiol ; 322(2): H260-H268, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919455

RESUMO

Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH), which may be secondary to blunted vascular function. Although women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient l-arginine bioavailability. Nine BL and nine WH women participated (age: 20 ± 2 vs. 22 ± 2 yr). Cutaneous microvascular function was assessed during 39°C local heating, whereas lactated Ringer's (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or l-arginine were infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of Nω-nitro-l-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, whereas combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVCmax). BL women had blunted %CVCmax and NO contribution to dilation during the 39°C plateau (P < 0.027 for both). BQ-123 improved this response through augmented NO-mediated dilation (P < 0.048 for both). BQ-788 and l-arginine did not alter the CVC responses (P > 0.835 for both) or the NO contribution (P > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women.NEW & NOTEWORTHY Cardiovascular disease remains a burden in the United States non-Hispanic black (BL) population, although its manifestation through blunted vasodilation in this population is different between men and women. Accordingly, this study determined that reduced microvascular function in young, BL women may be partially controlled by endothelin-1 (ET-1) type A receptors, although neither type B receptors nor insufficient l-arginine bioavailability seems to contribute to this response. Accordingly, further research is needed to better characterize these ET-1 related mechanisms and illuminate other pathways that may contribute to this disparate vascular function in young, BL women.


Assuntos
Afro-Americanos , Arginina/metabolismo , Doenças Cardiovasculares/etnologia , Endotelinas/metabolismo , Microvasos/metabolismo , Vasodilatação , Antagonistas dos Receptores de Endotelina/farmacologia , Feminino , Humanos , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Óxido Nítrico/metabolismo , Peptídeos Cíclicos/farmacologia , Receptores de Endotelina/metabolismo , Adulto Jovem
10.
Int J Mol Sci ; 22(24)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34948272

RESUMO

Chronic low-grade inflammation is involved in coronary atherosclerosis, presenting multiple clinical manifestations ranging from asymptomatic to stable angina, acute coronary syndrome, heart failure and sudden cardiac death. Coronary microvasculature consists of vessels with a diameter less than 500 µm, whose potential structural and functional abnormalities can lead to inappropriate dilatation and an inability to meet the required myocardium oxygen demands. This review focuses on the pathogenesis of coronary microvascular dysfunction and the capability of non-invasive screening methods to detect the phenomenon. Anti-inflammatory agents, such as statins and immunomodulators, including anakinra, tocilizumab, and tumor necrosis factor-alpha inhibitors, have been assessed recently and may constitute additional or alternative treatment approaches to reduce cardiovascular events in atherosclerotic heart disease characterized by coronary microvascular dysfunction.


Assuntos
Doença da Artéria Coronariana/sangue , Circulação Coronária/fisiologia , Microvasos/fisiologia , Síndrome Coronariana Aguda/fisiopatologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Morte Súbita Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Inflamação , Microcirculação/fisiologia , Microvasos/imunologia , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Fatores de Risco
11.
PLoS One ; 16(10): e0258479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648529

RESUMO

OBJECTIVE: To investigate the effects of axial length (AL) on the peripapillary microvascular density acquired from optical coherence tomography angiography (OCTA). METHODS: Retrospective observational study. A total of 111 eyes from 111 normal healthy subjects were examined. The subjects were divided into three groups according to the AL: Group 1 (AL: < 24.0 mm; 35 eyes), Group 2 (AL: 24.0-25.99 mm; 37 eyes), and Group 3 (AL: ≥ 26 mm; 39 eyes). Peripapillary OCTA images were acquired using 6× 6 mm angiography scans, and vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated automatically. VD and PD were compared among the three groups according to the distance from the optic disc (inner and outer rings). Linear regression analyses were also performed to identify clinical factors associated with average VD. RESULTS: The average ALs of Groups 1-3 were 23.33± 0.57, 25.05± 0.60, and 27.42± 0.82, respectively. Average VD (P = 0.009) and PD (P = 0.029) in the inner ring increased with increasing AL. However, average VD (P < 0.001) and PD (P < 0.001) in the outer ring decreased with AL increased; the same trends were found for the full areas (VD, p<0.001; PD, p = 0.001). Average VDs in the inner and outer rings were not associated (P = 0.938). CONCLUSIONS: Peripapillary VD and PD were significantly associated with AL. Depending on the distance from the disc, peripapillary VDs and PDs of the inner and outer rings were differentially affected by AL. Physicians should therefore consider the effects of AL in the analyses of peripapillary microvasculature.


Assuntos
Microvasos/fisiologia , Tomografia de Coerência Óptica/métodos , Adulto , Estudos de Casos e Controles , Feminino , Angiofluoresceinografia , Humanos , Modelos Lineares , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Disco Óptico/fisiologia , Estudos Retrospectivos
12.
J Therm Biol ; 100: 103038, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34503785

RESUMO

This paper analyzes the thermoelastic responses of skin tissue during laser irradiation based on a generalized dual-phase-lag (DPL) model. The method of separation of variables is utilized to obtain the analytical solutions for thermal and mechanical responses. The influences of some crucial parameters on temperature, displacement and stress evolutions are discussed, including the phase lag of heat flux, the phase lag of temperature gradient and the phase lag of laser pulse, the coupling factor between tissue and blood, the porosity of tissue, the equivalent diameter of tissue and the diameter of blood vessels. The generalized DPL bio-heat transfer model predicts different results from those by the classical DPL model and Pennes model. The equivalent diameter of tissue affects the coupling factor between tissue and blood, while the diameter of blood vessels mainly affects the porosity of tissue.


Assuntos
Elasticidade , Terapia com Luz de Baixa Intensidade , Modelos Teóricos , Temperatura Cutânea , Pele/efeitos da radiação , Humanos , Microvasos/fisiologia , Porosidade , Pele/irrigação sanguínea
13.
Physiol Rep ; 9(16): e14951, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34409753

RESUMO

The evaluation of the maximal oxygen uptake ( V ˙ O 2 max ) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention ( V ˙ O 2 max ), also do not improve in other health-related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V ˙ O 2 max responsiveness. Healthy sedentary participants engaged in a 6-week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non-responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V ˙ O 2 max , a greater increase in microvascular responsiveness in responders compared to non-responders was observed. Additionally, responders and non-responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome.


Assuntos
Adaptação Fisiológica , Exercício Físico , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Composição Corporal , Feminino , Coração/fisiologia , Frequência Cardíaca , Humanos , Masculino , Microvasos/fisiologia , Consumo de Oxigênio
14.
Am J Physiol Heart Circ Physiol ; 321(3): H592-H598, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415188

RESUMO

The endothelin-B (ETB) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E2) on ETB receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E2 exposure modulates ETB receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m2) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E2 (0.1 mg/day, Vivelle-Dot patch) was added back on days 4-10. We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on day 4 (GnRHant) and day 10 (GnRHant + E2) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ETB receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ETB receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ± 5%CVCmax, P = 0.004). E2 administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant + E2: 89 ± 8%CVCmax, P = 0.036). Furthermore, cutaneous vasodilatory responses during ETB receptor blockade were blunted after E2 administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVCmax, P = 0.047). These data demonstrate that ovarian hormones, specifically E2, modulate ETB receptor function and contribute to the regulation of microvascular endothelial function in young women.NEW & NOTEWORTHY The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.


Assuntos
Antagonistas do Receptor de Endotelina B/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Receptor de Endotelina B/metabolismo , Vasodilatação , Adulto , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Humanos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/fisiologia , Oligopeptídeos/farmacologia , Piperidinas/farmacologia , Pele/irrigação sanguínea
15.
Med Sci Monit ; 27: e930545, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34393219

RESUMO

BACKGROUND The incidence, pathogenesis, and prognostic effect of microvascular invasion on pancreatic ductal adenocarcinoma (PDAC) remain controversial. This study aimed to summarize the incidence, pathogenesis, role in clinical management, recurrence, and prognostic significance of microvascular invasion in PDAC. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Systematic literature searches were conducted using PubMed and Google Scholar up to February 2021. RESULTS Seventeen studies were included in the meta-analysis. The incidence of microvascular invasion was 49.0% (95% confidence interval [CI], 43.8-54.5%) among PDAC patients who underwent surgery. The weighted multivariate Cox proportional hazards model hazard ratio for disease-free survival of 8 studies was 1.78 (95% CI 1.53-2.08, P<0.001), and there was no statistically significant difference between the subgroups (P=0.477). The hazard ratio for overall survival of 14 studies was 1.49 (95% CI 1.27-1.74, P<0.001), and there was no statistically significant difference between the subgroups (P=0.676). CONCLUSIONS Microvascular invasion occurred in nearly half of PDAC patients after surgery and was closely related to disease-free and overall survival. Understanding the role of microvascular invasion in PDAC will help provide more personalized and effective preoperative or postoperative strategies to achieve better survival outcomes.


Assuntos
Carcinoma Ductal Pancreático/irrigação sanguínea , Carcinoma Ductal Pancreático/patologia , Invasividade Neoplásica/patologia , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/metabolismo , Intervalo Livre de Doença , Humanos , Incidência , Microvasos/fisiologia , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais
16.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199262

RESUMO

As the number of manned space flights increase, studies on the effects of microgravity on the human body are becoming more important. Due to the high expense and complexity of sending samples into space, simulated microgravity platforms have become a popular way to study these effects on earth. In addition, simulated microgravity has recently drawn the attention of regenerative medicine by increasing cell differentiation capability. These platforms come with many advantages as well as limitations. A main limitation for usage of these platforms is the lack of high-throughput capability due to the use of large cell culture vessels. Therefore, there is a requirement for microvessels for microgravity platforms that limit waste and increase throughput. In this work, a microvessel for commercial cell culture plates was designed. Four 3D printable (polycarbonate (PC), polylactic acid (PLA) and resin) and castable (polydimethylsiloxane (PDMS)) materials were assessed for biocompatibility with adherent and suspension cell types. PDMS was found to be the most suitable material for microvessel fabrication, long-term cell viability and proliferation. It also allows for efficient gas exchange, has no effect on cell culture media pH and does not induce hypoxic conditions. Overall, the designed microvessel can be used on simulated microgravity platforms as a method for long-term high-throughput biomedical studies.


Assuntos
Técnicas de Cultura de Células/métodos , Microvasos/fisiologia , Engenharia Tecidual/métodos , Simulação de Ausência de Peso , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Células Jurkat , Teste de Materiais , Microvasos/efeitos dos fármacos , Células THP-1
17.
Mol Vis ; 27: 466-479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321861

RESUMO

Purpose: To evaluate changes in the retinal microvascular network after posterior chamber phakic implantable collamer lens (ICL) surgery using optical coherence tomography angiography (OCTA) in patients with high myopia. Methods: Patients with high myopia who underwent ICL surgery were enrolled in this study. All patients underwent comprehensive ophthalmologic exams preoperatively and 1 week, 1 month, and 3 months postoperatively. The vascular densities (VDs) in the retina and the superficial and deep capillary plexuses of different annular and quadrantal areas were evaluated from OCTA images (Zeiss Cirrus 5000). Correlations between the variations in microvascular density and possible factors were further analyzed. Results: The study comprised 32 eyes of 32 patients. The mean age of the patients was 26.91±7.610 years (15 men and 17 women). A statistically significant reduction in microvascular density in the retina and the superficial plexus was found 1 week and 1 month postoperatively (p<0.05, repeated-measures ANOVA). Further fractal analysis found that the VD of the outer ring declined statistically significantly (p<0.05). A statistically significant decrease was also found in the inferior nasal sector 1 week postoperatively, with an overall decrease in all four quadrants 1 month postoperatively. The microvascular density recovered toward the baseline level 3 months postoperatively. No correlations were observed between the variation in microvascular density and the spherical equivalent (SE), axial length (AL), intraocular pressure (IOP), amplitude of accommodation (AA), or contrast sensitivity. Conclusions: Retinal microvascular density was decreased postoperatively and then recovered toward the baseline level after 3 months. ICL surgery may have a transient influence on the retinal microvascular network without affecting visual function.


Assuntos
Implante de Lente Intraocular , Microvasos/fisiologia , Miopia Degenerativa/cirurgia , Lentes Intraoculares Fácicas , Vasos Retinianos/fisiologia , Acomodação Ocular/fisiologia , Adolescente , Adulto , Comprimento Axial do Olho , Feminino , Angiofluoresceinografia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Adulto Jovem
18.
Science ; 373(6554)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34326210

RESUMO

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.


Assuntos
Envelhecimento/fisiologia , Envelhecimento Saudável , Longevidade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Tecido Adiposo , Animais , Vasos Sanguíneos/fisiologia , Composição Corporal , Distribuição da Gordura Corporal , Metabolismo dos Carboidratos , Carcinogênese , Endotélio Vascular/metabolismo , Fígado Gorduroso/patologia , Feminino , Inflamação/prevenção & controle , Fígado/patologia , Masculino , Camundongos , Densidade Microvascular , Microvasos/fisiologia , Osteoporose/prevenção & controle , Consumo de Oxigênio , Sarcopenia/prevenção & controle , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/sangue
19.
Sci Rep ; 11(1): 13411, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183707

RESUMO

Visualization and quantification of the skin microvasculature are important for studying the health of the human microcirculation. We correlated structural and pathophysiological changes of the dermal capillary-level microvasculature with age and blood pressure by using the reactive hyperemia optical coherence tomography angiography (RH-OCT-A) technique and evaluated both conventional OCT-A and the RH-OCT-A method as non-invasive imaging alternatives to histopathology. This observational pilot study acquired OCT-A and RH-OCT-A images of the dermal microvasculature of 13 young and 12 old healthy Caucasian female subjects. Two skin biopsies were collected per subject for histological analysis. The dermal microvasculature in OCT-A, RH-OCT-A, and histological images were automatically quantified and significant indications of vessel rarefaction in both old subjects and subjects with high blood pressure were observed by RH-OCT-A and histopathology. We showed that an increase in dermal microvasculature perfusion in response to reactive hyperemia was significantly lower in high blood pressure subjects compared to normal blood pressure subjects (117% vs. 229%). These results demonstrate that RH-OCT-A imaging holds functional information of the microvasculature with respect to physiological factors such as age and blood pressure that may help to monitor early disease progression and assess overall vascular health. Additionally, our results suggest that RH-OCT-A images may serve as a non-invasive alternative to histopathology for vascular analysis.


Assuntos
Envelhecimento/fisiologia , Angiografia/métodos , Pressão Sanguínea/fisiologia , Hiperemia/fisiopatologia , Hipertensão/fisiopatologia , Microcirculação/fisiologia , Microvasos/fisiologia , Pele/irrigação sanguínea , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Antebraço/irrigação sanguínea , Humanos , Hiperemia/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Microvasos/ultraestrutura , Projetos Piloto , Adulto Jovem
20.
PLoS Comput Biol ; 17(6): e1009164, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34170925

RESUMO

The vasculature is a dynamic structure, growing and regressing in response to embryonic development, growth, changing physiological demands, wound healing, tumor growth and other stimuli. At the microvascular level, network geometry is not predetermined, but emerges as a result of biological responses of each vessel to the stimuli that it receives. These responses may be summarized as angiogenesis, remodeling and pruning. Previous theoretical simulations have shown how two-dimensional vascular patterns generated by these processes in the mesentery are consistent with experimental observations. During early development of the brain, a mesh-like network of vessels is formed on the surface of the cerebral cortex. This network then forms branches into the cortex, forming a three-dimensional network throughout its thickness. Here, a theoretical model is presented for this process, based on known or hypothesized vascular response mechanisms together with experimentally obtained information on the structure and hemodynamics of the mouse cerebral cortex. According to this model, essential components of the system include sensing of oxygen levels in the midrange of partial pressures and conducted responses in vessel walls that propagate information about metabolic needs of the tissue to upstream segments of the network. The model provides insights into the effects of deficits in vascular response mechanisms, and can be used to generate physiologically realistic microvascular network structures.


Assuntos
Córtex Cerebral/irrigação sanguínea , Modelos Cardiovasculares , Modelos Neurológicos , Neovascularização Fisiológica , Animais , Córtex Cerebral/crescimento & desenvolvimento , Biologia Computacional , Simulação por Computador , Hemodinâmica/fisiologia , Camundongos , Microcirculação/fisiologia , Microvasos/anatomia & histologia , Microvasos/crescimento & desenvolvimento , Microvasos/fisiologia , Consumo de Oxigênio
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