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1.
Science ; 383(6683): eade8064, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38330107

RESUMO

Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.


Assuntos
Transportador 1 de Aminoácido Excitatório , Fibroblastos , Ereção Peniana , Pênis , Receptores Notch , Animais , Masculino , Camundongos , Circulação Sanguínea , Transportador 1 de Aminoácido Excitatório/metabolismo , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ereção Peniana/fisiologia , Pênis/irrigação sanguínea , Pênis/fisiologia , Receptores Notch/metabolismo , Transdução de Sinais , Vasoconstrição , Vasodilatação
2.
IEEE Trans Biomed Eng ; 71(2): 563-573, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37643096

RESUMO

OBJECTIVE: Reynolds Averaged Navier Stokes (RANS) models are often used as the basis for modeling blood damage in turbulent flows. To predict blood damage by turbulence stresses that are not resolved in RANS, a stress formulation that represents the corresponding scales is required. Here, we compare two commonly employed stress formulations: a scalar stress representation that uses Reynolds stresses as a surrogate for unresolved fluid stresses, and an effective stress formulation based on energy dissipation. METHODS: We conducted unsteady RANS simulations of the CentriMag blood pump with three different closure models and a Large Eddy Simulation (LES) for reference. We implemented both stress representations in all models and compared the resulting total stress distributions in Eulerian and Lagrangian frameworks. RESULTS: The Reynolds-stress-based approach overestimated the contribution of unresolved stresses in RANS, with differences between closure models of up to several orders of magnitude. With the dissipation-based approach, the total stresses predicted with RANS deviated by about 50% from the LES reference, which was more accurate than only considering resolved stresses. CONCLUSION: The Reynolds-stress-based formulation proved unreliable for estimating scalar stresses in our RANS simulations, while the dissipation-based approach provided an accuracy improvement over simply neglecting unresolved stresses. SIGNIFICANCE: Our results suggest that dissipation-based inclusion of unresolved stresses should be the preferred choice for blood damage modeling in RANS.


Assuntos
Circulação Sanguínea , Simulação por Computador
3.
PLoS One ; 18(10): e0289652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37856567

RESUMO

The heart is widely acknowledged as the unique driver of blood circulation. Recently, we discovered a flow-driving mechanism that can operate without imposed pressure, using infrared (IR) energy to propel flow. We considered the possibility that, by exploiting this mechanism, blood vessels, themselves, could propel flow. We verified the existence of this driving mechanism by using a three-day-old chick-embryo model. When the heart was stopped, blood continued to flow for approximately 50 minutes, albeit at a lower velocity. When IR was introduced, the postmortem flow increased from ~41.1 ± 25.6 µm/s to ~153.0 ± 59.5 µm/s (n = 6). When IR energy was diminished under otherwise physiological conditions, blood failed to flow. Hence, this IR-dependent, vessel-based flow-driving mechanism may indeed operate in the circulatory system, complementing the action of the heart.


Assuntos
Sistema Cardiovascular , Coração , Coração/fisiologia , Hemodinâmica , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Sanguínea , Pressão Sanguínea
4.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1908-1915, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282967

RESUMO

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).


Assuntos
Biomarcadores , Doença das Coronárias , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Muco , Adulto , Humanos , Biomarcadores/análise , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular , Farmacologia em Rede , RNA-Seq , Síndrome , Muco/metabolismo , Escarro/metabolismo , Circulação Sanguínea , Leucócitos Mononucleares/patologia , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica
5.
JACC Cardiovasc Imaging ; 16(9): 1149-1159, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37204381

RESUMO

BACKGROUND: Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. OBJECTIVES: This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. METHODS: The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. RESULTS: Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). CONCLUSIONS: Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.


Assuntos
Circulação Sanguínea , Infarto Encefálico , AVC Embólico , Átrios do Coração , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial/epidemiologia , Circulação Sanguínea/fisiologia , Infarto Encefálico/epidemiologia , AVC Embólico/epidemiologia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Fatores de Risco
6.
Exp Clin Transplant ; 21(2): 83-92, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36919717

RESUMO

OBJECTIVES: In the past decade, the implantable Doppler probe has been studied widely as a blood flow-monitoring device in reconstructive and transplant surgical specialities. Its utility as an effective postoperative monitoring technique is still debatable, with no clear guidelines in clinical practice. Here, we mapped the current evidence on the usefulness of the implantable Doppler probe as a blood flow-monitoring device. The objective was to present an up-to-date assessment of the benefits and limitations of using implantable Doppler probes in clinical and experimental clinical settings. MATERIALS AND METHODS: We conducted a literature search using the Cochrane Library and Healthcare Databases Advanced Search and using implantable Doppler probe, transplant, graft, and flap as key words. The search yielded 184 studies, with 73 studies included after exclusions. We evaluated, synthesized, and summarized the evidence from the studies in tabular form. RESULTS: There is clinical equipoise regarding the effectiveness of implantable Doppler probe as a flow sensing technique. The main reason is the lack of information and gaps in the evidence regarding the benefits and limitations of using implantable Doppler probes in clinical practice. CONCLUSIONS: The implantable Doppler probe has the potentialto be used as an adjunctpostoperativeblood flow-monitoring device. However, keeping in view of technical limitations, its signals should be interpreted alongside traditional clinical assessment techniques to determine the patency of microvascular anastomosis. Although evidence in this review will inform clinical practice in transplant and reconstructive surgical specialties, a prospective randomized controlled study with a larger patient cohort is required to evaluate the effectiveness of this probe in clinical settings.


Assuntos
Monitorização Fisiológica , Fluxo Sanguíneo Regional , Retalhos Cirúrgicos , Transplantes , Ultrassonografia Doppler , Humanos , Circulação Sanguínea , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/transplante , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Período Pós-Operatório , Estudos Prospectivos , Próteses e Implantes , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Transplante/instrumentação , Transplante/métodos , Transplantes/irrigação sanguínea , Ultrassonografia Doppler/instrumentação , Ultrassonografia Doppler/métodos
7.
Biomech Model Mechanobiol ; 22(3): 1095-1112, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36869925

RESUMO

Biological tissues receive oxygen and nutrients from blood vessels by developing an indispensable supply and demand relationship with the blood vessels. We implemented a synthetic tree generation algorithm by considering the interactions between the tissues and blood vessels. We first segment major arteries using medical image data and synthetic trees are generated originating from these segmented arteries. They grow into extensive networks of small vessels to fill the supplied tissues and satisfy the metabolic demand of them. Further, the algorithm is optimized to be executed in parallel without affecting the generated tree volumes. The generated vascular trees are used to simulate blood perfusion in the tissues by performing multiscale blood flow simulations. One-dimensional blood flow equations were used to solve for blood flow and pressure in the generated vascular trees and Darcy flow equations were solved for blood perfusion in the tissues using a porous model assumption. Both equations are coupled at terminal segments explicitly. The proposed methods were applied to idealized models with different tree resolutions and metabolic demands for validation. The methods demonstrated that realistic synthetic trees were generated with significantly less computational expense compared to that of a constrained constructive optimization method. The methods were then applied to cerebrovascular arteries supplying a human brain and coronary arteries supplying the left and right ventricles to demonstrate the capabilities of the proposed methods. The proposed methods can be utilized to quantify tissue perfusion and predict areas prone to ischemia in patient-specific geometries.


Assuntos
Algoritmos , Circulação Sanguínea , Simulação por Computador , Vasos Sanguíneos , Humanos , Animais , Encéfalo/irrigação sanguínea , Vasos Coronários/fisiologia , Artérias Cerebrais/fisiologia , Conjuntos de Dados como Assunto , Fenômenos Biomecânicos
8.
Anesthesiol Clin ; 41(1): 191-209, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36871999

RESUMO

Fluid therapy is an integral component of perioperative care and helps maintain or restore effective circulating blood volume. The principal goal of fluid management is to optimize cardiac preload, maximize stroke volume, and maintain adequate organ perfusion. Accurate assessment of volume status and volume responsiveness is necessary for appropriate and judicious utilization of fluid therapy. To accomplish this, static and dynamic indicators of fluid responsiveness have been widely studied. This review discusses the overarching goals of perioperative fluid management, reviews the physiology and parameters used to assess fluid responsiveness, and provides evidence-based recommendations on intraoperative fluid management.


Assuntos
Circulação Sanguínea , Hidratação , Hemodinâmica , Assistência Perioperatória , Humanos , Hidratação/métodos , Assistência Perioperatória/métodos , Volume Sistólico/fisiologia , Circulação Sanguínea/fisiologia , Hemodinâmica/fisiologia , Volume Cardíaco/fisiologia
9.
Sci Rep ; 12(1): 14610, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028657

RESUMO

Modeling of biological domains and simulation of biophysical processes occurring in them can help inform medical procedures. However, when considering complex domains such as large regions of the human body, the complexities of blood vessel branching and variation of blood vessel dimensions present a major modeling challenge. Here, we present a Voxelized Multi-Physics Simulation (VoM-PhyS) framework to simulate coupled heat transfer and fluid flow using a multi-scale voxel mesh on a biological domain obtained. In this framework, flow in larger blood vessels is modeled using the Hagen-Poiseuille equation for a one-dimensional flow coupled with a three-dimensional two-compartment porous media model for capillary circulation in tissue. The Dirac distribution function is used as Sphere of Influence (SoI) parameter to couple the one-dimensional and three-dimensional flow. This blood flow system is coupled with a heat transfer solver to provide a complete thermo-physiological simulation. The framework is demonstrated on a frog tongue and further analysis is conducted to study the effect of convective heat exchange between blood vessels and tissue, and the effect of SoI on simulation results.


Assuntos
Circulação Sanguínea/fisiologia , Temperatura Corporal/fisiologia , Corpo Humano , Modelos Biológicos , Capilares , Simulação por Computador , Temperatura Alta , Humanos , Imageamento Tridimensional
10.
Neoreviews ; 23(7): e486-e496, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35773505

RESUMO

The assessment of systemic blood flow is a complex and comprehensive process with clinical, laboratory, and technological components. Despite recent advancements in technology, there is no perfect bedside tool to quantify systemic blood flow in infants that can be used for clinical decision making. Each option has its own merits and limitations, and evidence on the reliability of these physiology-based assessment processes is evolving. This article provides an extensive review of the interpretation and limitations of methods to assess systemic blood flow in infants, highlighting the importance of a comprehensive and multimodal approach in this population.


Assuntos
Circulação Sanguínea , Humanos , Lactente , Recém-Nascido
11.
Prenat Diagn ; 42(9): 1133-1141, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35698885

RESUMO

OBJECTIVE: Fetuses with severe congenital heart disease (CHD) have altered blood flow patterns. Prior work to assess fetal combined cardiac output (CCO) is limited by sample size and lack of longitudinal gestational data. Our aim was to evaluate CCO in CHD fetuses to determine whether the presence of single ventricle (SV) physiology or aortic obstruction impacts fetal blood flow and cardiovascular hemodynamics. METHOD: Prospective study including singleton fetuses with CHD (n = 141) and controls (n = 118) who underwent a mid- and late-gestation fetal echocardiogram. Ventricular cardiac output was calculated using the standard computation. Combined cardiac output was derived as the sum of the right and left cardiac outputs and indexed to estimated fetal weight. RESULTS: Fetuses with two ventricle (2V) CHD had significantly higher CCO compared to controls and SV CHD fetuses. Fetuses with SV-CHD had similar CCO compared to controls. Fetuses with 2V-CHD and aortic obstruction had significantly higher CCO than fetuses with SV-CHD and aortic obstruction. CONCLUSION: Our findings suggest that the SV can compensate and increase CCO despite the lack of a second functioning ventricle, however, the degree of compensation may be insufficient to support the increased blood flow needed to overcome the hemodynamic and physiologic alternations seen with severe CHD.


Assuntos
Débito Cardíaco/fisiologia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/embriologia , Circulação Sanguínea/fisiologia , Estudos de Casos e Controles , Feminino , Feto , Idade Gestacional , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Gravidez , Estudos Prospectivos , Vacina Antivariólica , Ultrassonografia Pré-Natal
12.
Science ; 375(6581): eabi5965, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35143305

RESUMO

Dendritic cells (DCs) are crucial for initiating adaptive immune responses. However, the factors that control DC positioning and homeostasis are incompletely understood. We found that type-2 conventional DCs (cDC2s) in the spleen depend on Gα13 and adhesion G protein-coupled receptor family member-E5 (Adgre5, or CD97) for positioning in blood-exposed locations. CD97 function required its autoproteolytic cleavage. CD55 is a CD97 ligand, and cDC2 interaction with CD55-expressing red blood cells (RBCs) under shear stress conditions caused extraction of the regulatory CD97 N-terminal fragment. Deficiency in CD55-CD97 signaling led to loss of splenic cDC2s into the circulation and defective lymphocyte responses to blood-borne antigens. Thus, CD97 mechanosensing of RBCs establishes a migration and gene expression program that optimizes the antigen capture and presentation functions of splenic cDC2s.


Assuntos
Células Dendríticas/fisiologia , Eritrócitos/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Baço/citologia , Baço/imunologia , Actinas/metabolismo , Animais , Apresentação de Antígeno , Antígenos/imunologia , Circulação Sanguínea , Antígenos CD55/sangue , Antígenos CD55/metabolismo , Movimento Celular , Células Dendríticas/imunologia , Eritrócitos/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Homeostase , Fatores Reguladores de Interferon/metabolismo , Ligantes , Camundongos , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Baço/irrigação sanguínea , Baço/metabolismo , Transcrição Gênica , Transcriptoma
14.
J Ethnopharmacol ; 285: 114896, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896207

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 'Cold feeling' is a subjective feeling of unusual coldness that aggravates fatigue, stiffness, and other symptoms, thereby reducing quality of life. Tokishakuyakusan (TSS) is a Kampo medicine reported to improve cold feeling and is used to treat symptoms aggravated by cold feeling. However, the mechanism of action of TSS is unclear. Cold feeling may involve reduced blood flow and subsequent inhibition of heat transport. Therefore, elucidating the effects of TSS on blood flow is one of the most important research topics for clarifying the mechanism of action of TSS. AIM OF THE STUDY: We aimed to evaluate the effect of TSS on recovery from lowered body temperature by the immersion of rats in cold water and to clarify the involvement of blood flow in the action of TSS. MATERIALS AND METHODS: After female Wistar rats underwent 9 days of low room temperature stress loading (i.e. room temperature of 18 °C), they were subjected to immersion in cold water (15 °C) for 15 min. Body surface temperature, rectal temperature, and plantar temperature were measured before and after immersion in cold water. Blood flow was measured before and after immersion in cold water without low room temperature stress loading. TSS (0.5 g/kg or 1 g/kg) or the vehicle (i.e. distilled water) was orally administered once daily for 10 days for the measurement of body temperature or once 30 min before immersion in cold water for the measurement of blood flow. In addition, we examined the effect of TSS on calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) cells, the effect of TSS ingredients on transient receptor potential (TRP) channels, and the effect of TSS ingredients on the membrane potential of vascular smooth muscle cells and evaluated the mechanism of the effects of TSS on blood flow. RESULTS: Body temperature and blood flow decreased after immersion in cold water and then recovered over time. A comparison of body temperature at each timepoint or area under the curve showed that TSS (1 g/kg) accelerated the recovery of body surface temperature, rectal temperature, and blood flow. TSS significantly increased CGRP release from DRG cells, which disappeared after pretreatment with HC-030031 (a transient receptor potential ankyrin 1 [TRPA1] antagonist). The effects of seven TSS ingredients on TRP channels were examined. The agonistic effect on TRPA1 was observed for atractylodin, atractylodin carboxylic acid and levistolide A. Among the TSS ingredients, atractylodin carboxylic acid had significant hyperpolarising effects. CONCLUSIONS: The mechanism by which TSS accelerates the recovery of lowered body temperature in rats after immersion in cold water may involve the acceleration of the recovery of lowered blood flow. Increased CGRP release from DRG cells by TSS, TRPA1 activation by TSS ingredients, and membrane potential changes in vascular smooth muscle cells caused by TSS ingredients are part of the mechanism of action of TSS. These findings may partly contribute to the interpretation of the beneficial effects of TSS on cold feeling.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Temperatura Baixa , Medicamentos de Ervas Chinesas/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Feminino , Gânglios Espinais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Kampo , Miócitos de Músculo Liso/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , Artérias Umbilicais/citologia
15.
Circ Res ; 130(1): 67-79, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34789007

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are generated by back splicing of mostly mRNAs and are gaining increasing attention as a novel class of regulatory RNAs that control various cellular functions. However, their physiological roles and functional conservation in vivo are rarely addressed, given the inherent challenges of their genetic inactivation. Here, we aimed to identify locus conserved circRNAs in mice and humans, which can be genetically deleted due to retained intronic elements not contained in the mRNA host gene to eventually address functional conservation. METHODS AND RESULTS: Combining published endothelial RNA-sequencing data sets with circRNAs of the circATLAS databank, we identified locus-conserved circRNA retaining intronic elements between mice and humans. CRISPR/Cas9 mediated genetic depletion of the top expressed circRNA cZfp292 resulted in an altered endothelial morphology and aberrant flow alignment in the aorta in vivo. Consistently, depletion of cZNF292 in endothelial cells in vitro abolished laminar flow-induced alterations in cell orientation, paxillin localization and focal adhesion organization. Mechanistically, we identified the protein SDOS (syndesmos) to specifically interact with cZNF292 in endothelial cells by RNA-affinity purification and subsequent mass spectrometry analysis. Silencing of SDOS or its protein binding partner Syndecan-4, or mutation of the SDOS-cZNF292 binding site, prevented laminar flow-induced cytoskeletal reorganization thereby recapitulating cZfp292 knockout phenotypes. CONCLUSIONS: Together, our data reveal a hitherto unknown role of cZNF292/cZfp292 in endothelial flow responses, which influences endothelial shape.


Assuntos
Proteínas de Ligação a DNA , Células Endoteliais , Endotélio Vascular , RNA Circular , Fatores de Transcrição , Animais , Humanos , Camundongos , Circulação Sanguínea , Proteínas de Ligação a DNA/genética , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Endogâmicos C57BL , Ligação Proteica , RNA Circular/genética , RNA Circular/metabolismo , Sindecana-4/metabolismo , Fatores de Transcrição/genética
16.
J Nutr Biochem ; 99: 108862, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34530111

RESUMO

Lycopene (Ly) is a kind of hydrocarbon, which belongs to the family of tetraterpene carotene and exists in red fruits and vegetables. The decrease of capillary density and blood flow with age is a significant reason for the increase of mortality and morbidity. Herein, our study aims to explore the effects of Ly (a bioactive food compound) on vascular aging in vitro and in vivo and its potential mechanisms. The cytological results showed that Ly could promote the proliferation of human umbilical vein endothelial cell (HUVECs) and enhance the ability of HUVECs to form capillary-like structures. Furthermore, the expression of SIRT1 in aged HUVECs was up-regulated. In vivo, aging rats showed signs of insulin resistance and blood vessel damage. Additionally, the capillary density and blood flow were reduced during the vascular aging process in both D-gal-induced and naturally aging muscle. However, when Ly was given, these conditions could be reversed. Simultaneously, the contents of ATP, lactic acid and pyruvic acid were determined, and it was found that Ly could promote angiogenesis by increasing the utilization rate of glucose and promoting energy metabolism. Finally, in the insulin resistance cell model, we knocked down the SIRT1 and administrated with Ly, and found that it couldn't restore insulin transdution. In conclusion, all the data in this study demonstrate that Ly could reactivate SIRT1 and improve insulin resistance, which was a reversible cause of vascular aging.


Assuntos
Envelhecimento/efeitos dos fármacos , Resistência à Insulina , Licopeno/administração & dosagem , Músculo Esquelético/irrigação sanguínea , Sirtuína 1/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Circulação Sanguínea , Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Densidade Microvascular , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-34303334

RESUMO

BACKGROUND: Insulin resistance is a well-known predictor and risk factor for type 2 diabetes mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. OBJECTIVE: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). METHODS: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. RESULTS: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC), platelet count, lipid parameters and body mass index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C), triglyceride (TG), and positively correlated with high-density lipoprotein- cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C and BMI, and positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA-ß) was positively correlated with WBC count, platelet count, TC, LDL-C and TG. The insulinogenic index was positively correlated with WBC count, platelet count and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. CONCLUSION: Cardinal rheological parameters reflected insulin resistance and release even in young healthy Japanese individuals within the physiological range of glycemic control.


Assuntos
Circulação Sanguínea/fisiologia , Glicemia/metabolismo , Resistência à Insulina/fisiologia , Adulto , Contagem de Eritrócitos , Feminino , Teste de Tolerância a Glucose , Voluntários Saudáveis , Hematócrito , Humanos , Secreção de Insulina/fisiologia , Japão , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Reologia , Adulto Jovem
19.
Artif Organs ; 46(1): 71-82, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34287976

RESUMO

The objective of this study is to identify the preload and afterload sensitivity of the ReinHeart TAH 2.0. For adequate left-right flow balance, the concept of a reduced right stroke volume (by about 10%) and active adaption of the right diastole duration are evaluated concerning the controllability of the flow balance. This study used an active mock circulation loop to test a wide range of preload and afterload conditions. Preload sensitivity was tested at atrial pressures (APs) between 4 and 20 mm Hg. Left afterload was varied in a range of 60-140 mm Hg mean aortic pressure (MAP), right afterload was simulated between 15 and 40 mm Hg. Four scenarios were developed to verify that the flow difference fully covers the defined target range of 0-1.5 L/min. Although a positive correlation between inlet pressure and flow is identified for the right pump chamber, the left pump chamber already fills completely at an inlet pressure of 8-10 mm Hg. With increasing afterload, both the left and right flow decrease. A positive flow balance (left flow exceeds right flow) is achieved over the full range of tested afterloads. At high APs, the flow difference is limited to a maximum of 0.7 L/min. The controllability of flow balance was successfully evaluated in four scenarios, revealing that a positive flow difference can be achieved over the full range of MAPs. Under physiological test conditions, the linear relationship between flow and heart rate was confirmed, ensuring good controllability of the TAH.


Assuntos
Circulação Sanguínea , Coração Artificial , Desenho de Prótese , Pressão Sanguínea , Frequência Cardíaca , Hidrodinâmica , Modelos Cardiovasculares
20.
Medicine (Baltimore) ; 100(47): e27997, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964796

RESUMO

RATIONALE: Perioperative administration of tranexamic acid has been suggested to reduce bleeding and blood transfusion requirements in patients undergoing orthopedic surgery. Despite being sporadic, the potential risk for thrombotic complications cannot be ignored. However, intracardiac thrombosis associated with tranexamic acid administration is rare. We described a case of circulatory collapse caused by intracardiac thrombosis associated with tranexamic acid administration for a scheduled knee arthroplasty. PATIENT CONCERNS: A 62-year-old male patient was scheduled for a right knee arthroplasty. He had a history of hypertension and had undergone surgery for treatment of right femur fracture 30 years previously. Other than a high platelet count (498 × 109/L), results of laboratory investigations were within normal limits. The ultrasonic examination of both lower limbs showed no thrombosis. Upon sterilizing the surgical area, tranexamic acid (1.6 g) was intravenously administered after induction of anesthesia and intubation. Then the patient had a sudden circulatory collapse. Through cardiopulmonary resuscitation, the patient recovered spontaneous circulation. Transesophageal echocardiography revealed extensive thrombosis in the right atrium and ventricle. DIAGNOSIS: Circulation collapse caused by intracardiac thrombosis. INTERVENTIONS: Thrombolytic therapy was recommended after urgent multidisciplinary consultation. Thus, urokinase was administered intravenously. Fifty minutes after thrombolysis, the mass in ventricle disappeared. A shrunken mass was observed in the right atrium. After another half an hour, no abnormal echoes were seen in the right heart chambers. OUTCOMES: The patient was discharged after 43 days without any organ dysfunction. LESSONS: This case reminds clinicians that perioperative tranexamic acid administration may increase the risk of thrombosis, which needs focused attention from anesthesiologists. Prompt transesophageal echocardiography examination should be done to allow immediate diagnosis and effective thrombolysis therapy when unexplained cardiac arrest occurs during anesthesia.


Assuntos
Antifibrinolíticos/efeitos adversos , Artroplastia do Joelho/métodos , Circulação Sanguínea/efeitos dos fármacos , Epinefrina/administração & dosagem , Choque/etiologia , Trombose/induzido quimicamente , Ácido Tranexâmico/efeitos adversos , Antifibrinolíticos/administração & dosagem , Perda Sanguínea Cirúrgica , Reanimação Cardiopulmonar , Ecocardiografia Transesofagiana , Humanos , Injeções Intraventriculares , Masculino , Pessoa de Meia-Idade , Trombose/diagnóstico por imagem , Ácido Tranexâmico/administração & dosagem
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