RESUMO
The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies.
Assuntos
Osso e Ossos , Homeostase , Articulações , Vasos Linfáticos , Humanos , Homeostase/fisiologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Vasos Linfáticos/patologia , Vasos Linfáticos/fisiopatologia , Vasos Linfáticos/metabolismo , Vasos Linfáticos/fisiologia , Animais , Articulações/patologia , Articulações/metabolismo , Articulações/irrigação sanguínea , Vasos Sanguíneos/patologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Artropatias/patologia , Artropatias/fisiopatologia , Artropatias/metabolismoRESUMO
The increasing burden of vascular dysfunction on healthcare systems worldwide results in higher morbidity and mortality rates across pathologies, including cardiovascular diseases. Vasculopathy is suggested to be caused by the dysregulation of vascular niches, a microenvironment of vascular structures comprising anatomical structures, extracellular matrix components, and various cell populations. These elements work together to ensure accurate control of the vascular network. In recent years, autophagy has been recognized as a crucial regulator of the vascular microenvironment responsible for maintaining basic cell functions such as proliferation, differentiation, replicative senescence, and apoptosis. Experimental studies indicate that autophagy activation can be enhanced or inhibited in various pathologies associated with vascular dysfunction, suggesting that autophagy plays both beneficial and detrimental roles. Here, we review and assess the principles of autophagy organization and regulation in non-tumor vascular niches. Our analysis focuses on significant figures in the vascular microenvironment, highlighting the role of autophagy and summarizing evidence that supports the systemic or multiorgan nature of the autophagy effects. Finally, we discuss the critical organizational and functional aspects of the vasculogenic niche, specifically in relation to autophagy. The resulting dysregulation of the vascular microenvironment contributes to the development of vascular dysfunction.
Assuntos
Autofagia , Homeostase , Autofagia/fisiologia , Humanos , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/patologiaRESUMO
Optimizing the regeneration process of surgically created anastomoses (blood vessels, intestines, nerves) is an important topic in surgical research. One of the most interesting parameter groups is related to the biomechanical properties of the anastomoses. Depending on the regeneration process and its influencing factors, tensile strength and other biomechanical features may change during the healing process. Related to the optimal specimen size, the range and accuracy of measurements, and applicability, we have developed a custom-tailored microcontroller-based device. In this paper, we describe the hardware and software configuration of the latest version of the device, including experiences and comparative measurements of tensile strength and elasticity of artificial materials and biopreparate tissue samples. The machine we developed was made up of easily obtainable parts and can be easily reproduced on a low budget. The basic device can apply a force of up to 40 newtons, and can grasp a 0.05-1 cm wide, 0.05-1 cm thick tissue. The length of the test piece on the rail should be between 0.3 and 5 cm. Low production cost, ease of use, and detailed data recording make it a useful tool for experimental surgical research.
Assuntos
Anastomose Cirúrgica , Elasticidade , Intestinos , Resistência à Tração , Intestinos/fisiologia , Anastomose Cirúrgica/instrumentação , Regeneração/fisiologia , Animais , Humanos , Vasos Sanguíneos/fisiologia , Fenômenos Biomecânicos/fisiologiaRESUMO
Printing human tissues and organs replete with biomimetic vascular networks is of growing interest. While it is possible to embed perfusable channels within acellular and densely cellular matrices, they do not currently possess the biomimetic architectures found in native vessels. Here, coaxial sacrificial writing into functional tissues (co-SWIFT) is developed, an embedded bioprinting method capable of generating hierarchically branching, multilayered vascular networks within both granular hydrogel and densely cellular matrices. Coaxial printheads are designed with an extended core-shell configuration to facilitate robust core-core and shell-shell interconnections between printed branching vessels during embedded bioprinting. Using optimized core-shell ink combinations, biomimetic vessels composed of a smooth muscle cell-laden shell that surrounds perfusable lumens are coaxially printed into granular matrices composed of: 1) transparent alginate microparticles, 2) sacrificial microparticle-laden collagen, or 3) cardiac spheroids derived from human induced pluripotent stem cells. Biomimetic blood vessels that exhibit good barrier function are produced by seeding these interconnected lumens with a confluent layer of endothelial cells. Importantly, it is found that co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of vascularized organ-specific tissues for drug testing, disease modeling, and therapeutic use.
Assuntos
Materiais Biomiméticos , Bioimpressão , Engenharia Tecidual , Humanos , Materiais Biomiméticos/química , Bioimpressão/métodos , Engenharia Tecidual/métodos , Alginatos/química , Células-Tronco Pluripotentes Induzidas/citologia , Hidrogéis/química , Alicerces Teciduais/química , Biomimética/métodos , Colágeno/química , Miócitos de Músculo Liso/citologia , Vasos Sanguíneos/citologia , Vasos Sanguíneos/fisiologia , Células Endoteliais da Veia Umbilical Humana , Animais , Esferoides Celulares/citologiaRESUMO
As a critical part of the circulatory system, blood vessels transport oxygen and nutrients to every corner of the body, nourishing each cell, and also remove waste and toxins. Defects in vascular development and function are closely associated with many diseases, such as heart disease, stroke, and atherosclerosis. In the nervous system, the nervous and vascular systems are intricately connected in both development and function. First, peripheral blood vessels and nerves exhibit parallel distribution patterns. In the central nervous system (CNS), nerves and blood vessels form a complex interface known as the neurovascular unit. Second, the vascular system employs similar cellular and molecular mechanisms as the nervous system for its development. Third, the development and function of CNS vasculature are tightly regulated by CNS-specific signaling pathways and neural activity. Additionally, vascular endothelial cells within the CNS are tightly connected and interact with pericytes, astrocytes, neurons, and microglia to form the blood-brain barrier (BBB). The BBB strictly controls material exchanges between the blood and brain, maintaining the brain's microenvironmental homeostasis, which is crucial for the normal development and function of the CNS. Here, we comprehensively summarize research on neural regulation of vascular and BBB development and propose directions for future research.
Assuntos
Barreira Hematoencefálica , Humanos , Animais , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/crescimento & desenvolvimento , Neurônios/metabolismo , Células Endoteliais/metabolismo , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/fisiologia , Transdução de SinaisRESUMO
BACKGROUND: As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis. METHODS: Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module's expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis. RESULTS: Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion. CONCLUSIONS: We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.
Assuntos
MicroRNAs , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , MicroRNAs/sangue , MicroRNAs/genética , Idoso , Adulto , Idoso de 80 Anos ou mais , Redes Reguladoras de Genes , Regulação da Expressão Gênica , Vasos Sanguíneos/fisiologia , Estudos de Coortes , Ontologia Genética , Perfilação da Expressão GênicaRESUMO
Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.
Assuntos
Regeneração , Medicina Regenerativa , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Medicina Regenerativa/métodos , Animais , Doenças Vasculares/terapia , Doenças Vasculares/fisiopatologia , Bioimpressão/métodos , Vasos Sanguíneos/fisiologia , Impressão TridimensionalRESUMO
Vascular tissue engineering is a promising approach for regenerating damaged blood vessels and developing new therapeutic approaches for heart disease treatment. To date, different sources of cells have been recognized that offer assistance within the recovery of heart supply routes and veins with distinctive capacities and are compelling for heart regeneration. However, some challenges still remain that need to be overcome to establish the full potential application of these cells. In this paper, we review the different cell sources used for vascular tissue engineering, focusing on extraembryonic tissue-derived cells (ESCs), and elucidate their roles in cardiovascular disease. In addition, we highlight the intricate interplay between mechanical and biochemical factors in regulating mesenchymal stem cell (MSC) differentiation, offering insights into optimizing their application in vascular tissues.
Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais , Regeneração , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regeneração/fisiologia , Animais , Vasos Sanguíneos/citologia , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologiaRESUMO
Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.
Assuntos
Vasos Sanguíneos , Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Vasos Sanguíneos/citologia , Vasos Sanguíneos/fisiologia , Células Endoteliais/citologia , Dispositivos Lab-On-A-Chip , Neovascularização FisiológicaRESUMO
Solitary wave solutions are of great interest to bio-mathematicians and other scientists because they provide a basic description of nonlinear phenomena with many practical applications. They provide a strong foundation for the development of novel biological and medical models and therapies because of their remarkable behavior and persistence. They have the potential to improve our comprehension of intricate biological systems and help us create novel therapeutic approaches, which is something that researchers are actively investigating. In this study, solitary wave solutions of the nonlinear Murray equation will be discovered using a modified extended direct algebraic method. These solutions represent a uniform variation in blood vessel shape and diameter that can be used to stimulate blood flow in patients with cardiovascular disease. These solutions are newly in the literature, and give researchers an important tool for grasping complex biological systems. To see how the solitary wave solutions behave, graphs are displayed using Matlab.
Assuntos
Dinâmica não Linear , Humanos , Modelos Cardiovasculares , Vasos Sanguíneos/fisiologia , Velocidade do Fluxo Sanguíneo , AlgoritmosRESUMO
The transplantation of vascular grafts has emerged as a prevailing approach to address vascular disorders. However, the development of small-diameter vascular grafts is still in progress, as they serve in a more complicated mechanical environment than their counterparts with larger diameters. The biocompatibility and functional characteristics of small-diameter vascular grafts have been well developed; however, mismatch in mechanical properties between the vascular grafts and native arteries has not been accomplished, which might facilitate the long-term patency of small-diameter vascular grafts. From a point of view in mechanics, mimicking the nonlinear elastic mechanical behavior exhibited by natural blood vessels might be the state-of-the-art in designing vascular grafts. This review centers on elucidating the nonlinear elastic behavior of natural blood vessels and vascular grafts. The biological functionality and limitations associated with as-reported vascular grafts are meticulously reviewed and the future trajectory for fabricating biomimetic small-diameter grafts is discussed. This review might provide a different insight from the traditional design and fabrication of artificial vascular grafts.
Assuntos
Prótese Vascular , Vasos Sanguíneos , Elasticidade , Humanos , Vasos Sanguíneos/fisiologia , Animais , Materiais Biocompatíveis/químicaRESUMO
A profound investigation of the interaction mechanics between blood vessels and guidewires is necessary to achieve safe intervention. An interactive force model between guidewires and blood vessels is established based on cardiovascular fluid dynamics theory and contact mechanics, considering two intervention phases (straight intervention and contact intervention at a corner named "J-vessel"). The contributing factors of the force model, including intervention conditions, guidewire characteristics, and intravascular environment, are analyzed. A series of experiments were performed to validate the availability of the interactive force model and explore the effects of influential factors on intervention force. The intervention force data were collected using a 2-DOF mechanical testing system instrumented with a force sensor. The guidewire diameter and material were found to significantly impact the intervention force. Additionally, the intervention force was influenced by factors such as blood viscosity, blood vessel wall thickness, blood flow velocity, as well as the interventional velocity and interventional mode. The experiment of the intervention in a coronary artery physical vascular model confirms the practicality validation of the predicted force model and can provide an optimized interventional strategy for vascular interventional surgery. The enhanced intervention strategy has resulted in a considerable reduction of approximately 21.97 % in the force exerted on blood vessels, effectively minimizing the potential for complications associated with the interventional surgery.
Assuntos
Fenômenos Mecânicos , Vasos Sanguíneos/fisiologia , Modelos Cardiovasculares , Hidrodinâmica , Humanos , Fenômenos Biomecânicos , Modelos Biológicos , Vasos Coronários/fisiologiaRESUMO
Melt Electrowriting (MEW) is a continuously growing manufacturing platform. Its advantage is the consistent production of micro- to nanometer fibers, that stack intricately, forming complex geometrical shapes. MEW allows tuning of the mechanical properties of constructs via the geometry of deposited fibers. Due to this, MEW can create complex mechanics only seen in multi-material compounds and serve as guiding structures for cellular alignment. The advantage of MEW is also shown in combination with other biotechnological manufacturing methods to create multilayered constructs that increase mechanical approximation to native tissues, biocompatibility, and cellular response. These features make MEW constructs a perfect candidate for small-diameter vascular graft structures. Recently, studies have presented fascinating results in this regard, but is this truly the direction that tubular MEW will follow or are there also other options on the horizon? This perspective will explore the origins and developments of tubular MEW and present its growing importance in the field of artificial small-diameter vascular grafts with mechanical modulation and improved biomimicry and the impact of it in convergence with other manufacturing methods and how future technologies like AI may influence its progress.
Assuntos
Prótese Vascular , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Vasos Sanguíneos/fisiologia , Materiais Biocompatíveis/química , Animais , Alicerces Teciduais/químicaRESUMO
The dialysis catheter indwelling in human bodies has a high risk of inducing thrombus and stenosis. Biomechanical research showed that such physiological complications are triggered by the wall shear stress of the vascular vessel. This study aimed to assess the impact of CVC implantation on central venous haemodynamics and the potential alterations in the haemodynamic environment related to thrombus development. The SVC structure was built from the images from computed tomography. The blood flow was calculated using the Carreau model, and the fluid domain was determined by CFD. The vascular wall and the CVC were computed using FEA. The elastic interaction between the vessel wall and the flow field was considered using FSI simulation. With consideration of the effect of coupling, it was shown that the catheter vibrated in the vascular systems due to the periodic variation of blood pressure, with an amplitude of up to 10% of the vessel width. Spiral flow was observed along the catheter after CVC indwelling, and recirculation flow appeared near the catheter tip. High OSI and WSS regions occurred at the catheter tip and the vascular junction. The arterial lumen tip had a larger effect on the WSS and OSI values on the vascular wall. Considering FSI simulation, the movement of the catheter inside the blood flow was simulated in the deformable vessel. After CVC indwelling, spiral flow and recirculation flow were observed near the regions with high WSS and OSI values.
Assuntos
Modelos Cardiovasculares , Diálise Renal , Humanos , Hemodinâmica/fisiologia , Elasticidade , Estresse Mecânico , Simulação por Computador , Velocidade do Fluxo Sanguíneo/fisiologia , Vasos Sanguíneos/fisiologiaRESUMO
The understanding of the function of perivascular adipose tissue (PVAT) in vascular aging has significantly changed due to the increasing amount of information regarding its biology. Adipose tissue surrounding blood vessels is increasingly recognized as a key regulator of vascular disorders. It has significant endocrine and paracrine effects on the vasculature and is mediated by the production of a variety of bioactive chemicals. It also participates in a number of pathological regulatory processes, including oxidative stress, immunological inflammation, lipid metabolism, vasoconstriction, and dilation. Mechanisms of homeostasis and interactions between cells at the local level tightly regulate the function and secretory repertoire of PVAT, which can become dysregulated during vascular aging. The PVAT secretion group changes from being reducing inflammation and lowering cholesterol to increasing inflammation and increasing cholesterol in response to systemic or local inflammation and insulin resistance. In addition, the interaction between the PVAT and the vasculature is reciprocal, and the biological processes of PVAT are directly influenced by the pertinent indicators of vascular aging. The architectural and biological traits of PVAT, the molecular mechanism of crosstalk between PVAT and vascular aging, and the clinical correlation of vascular age-related disorders are all summarized in this review. In addition, this paper aims to elucidate and evaluate the potential benefits of therapeutically targeting PVAT in the context of mitigating vascular aging. Furthermore, it will discuss the latest advancements in technology used for targeting PVAT.
Assuntos
Tecido Adiposo , Envelhecimento , Vasos Sanguíneos , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Animais , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/metabolismo , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologiaRESUMO
The magnitude of vascular residual stress, an inherent characteristic exclusive to the vasculature, exhibits a strong correlation with vascular compliance, tensile resistance, vascular rigidity, and vascular remodeling subsequent to vascular transplantation. Vascular residual stress can be quantified by evaluating the magnitude of the opening angle within the vascular ring. For decellularized vessels, the vascular ring's opening angle diminishes, consequently reducing residual stress. The decellularization process induces a laxity in the vascular fiber structure within decellularized vessels. To investigate the interrelation between the magnitude of residual stress and the microstructure as well as mechanical properties of elastin and collagen within blood vessels, this study employed fresh blood vessels, stress-relieved vessels, and sections of decellularized blood vessels. Structural scanning and force map experiments on the surface of the sections were conducted using atomic force microscopy (AFM). The findings revealed well-organized arrangements of elastin and collagen within fresh vessels, wherein the regularity of collagen and elastin exhibited variability as residual stress declined. Furthermore, both stress-relieved and decellularized vessel sections exhibited a reduction in the mean Young's modulus to varying extents in comparison to fresh vessels. The validity of our experimental results was further corroborated through finite element simulations. Hence, residual stress assumes a crucial role in upholding the structural stability of blood vessels, and the intricate association between residual stress and the microstructural and micromechanical properties of blood vessels holds significant implications for comprehending the impact of vascular diseases on vascular structure and advancing the development of biomimetic artificial blood vessels that replicate residual stress. RESEARCH HIGHLIGHTS: In this inquiry, we scrutinized the interconnection amid vascular residual stress and the microscale and nanoscale aspects of vascular structure and mechanical function, employing AFM. We ascertained that residual stress assumes a pivotal role in upholding vascular microstructure and mechanical attributes. The experimental outcomes were subsequently validated through finite element simulation.
Assuntos
Vasos Sanguíneos , Colágeno , Elastina , Microscopia de Força Atômica , Estresse Mecânico , Microscopia de Força Atômica/métodos , Elastina/análise , Animais , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/ultraestrutura , Módulo de Elasticidade , Fenômenos BiomecânicosRESUMO
In vitro blood vessel models are significant for disease modeling, drug assays, and therapeutic development. Microfluidic technologies allow to create physiologically relevant culture models reproducing the features of the in vivo vascular microenvironment. However, current microfluidic technologies are limited by impractical rectangular cross-sections and single or nonsynchronous compound mechanical stimuli. This study proposes a new strategy for creating round-shaped deformable soft microfluidic channels to serve as artificial in vitro vasculature for developing in vitro models with vascular physio-mechanical microenvironments. Endothelial cells seeded into vascular models are used to assess the effects of a remodeled in vivo mechanical environment. Furthermore, a 3D stenosis model is constructed to recapitulate the flow disturbances in atherosclerosis. Soft microchannels can also be integrated into traditional microfluidics to realize multifunctional composite systems. This technology provides new insights into applying microfluidic chips and a prospective approach for constructing in vitro blood vessel models.
Assuntos
Células Endoteliais da Veia Umbilical Humana , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Microfluídica/métodos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pressão , Animais , Dispositivos Lab-On-A-Chip , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Vasos Sanguíneos/fisiologiaRESUMO
Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.
Assuntos
Nadadeiras de Animais , Macrófagos , Neovascularização Fisiológica , Regeneração , Peixe-Zebra , Animais , Macrófagos/metabolismo , Nadadeiras de Animais/fisiologia , Nadadeiras de Animais/irrigação sanguínea , Vasos Sanguíneos/fisiologia , Células Endoteliais/metabolismoRESUMO
Vascular tone regulation is a crucial aspect of cardiovascular physiology, with significant implications for overall cardiovascular health. However, the precise physiological mechanisms governing smooth muscle cell contraction and relaxation remain uncertain. The complexity of vascular tone regulation stems from its multiscale and multifactorial nature, involving global hemodynamics, local flow conditions, tissue mechanics, and biochemical pathways. Bridging this knowledge gap and translating it into clinical practice presents a challenge. In this paper, a computational model is presented to integrate chemo-mechano-biological pathways with cardiovascular biomechanics, aiming to unravel the intricacies of vascular tone regulation. The computational framework combines an algebraic description of global hemodynamics with detailed finite element analyses at the scale of vascular segments for describing their passive and active mechanical response, as well as the molecular transport problem linked with chemo-biological pathways triggered by wall shear stresses. Their coupling is accounted for by considering a two-way interaction. Specifically, the focus is on the role of nitric oxide-related molecular pathways, which play a critical role in modulating smooth muscle contraction and relaxation to maintain vascular tone. The computational framework is employed to examine the interplay between localized alterations in the biomechanical response of a specific vessel segment-such as those induced by calcifications or endothelial dysfunction-and the broader global hemodynamic conditions-both under basal and altered states. The proposed approach aims to advance our understanding of vascular tone regulation and its impact on cardiovascular health. By incorporating chemo-mechano-biological mechanisms into in silico models, this study allows us to investigate cardiovascular responses to multifactorial stimuli and incorporate the role of adaptive homeostasis in computational biomechanics frameworks.
Assuntos
Simulação por Computador , Análise de Elementos Finitos , Modelos Cardiovasculares , Fenômenos Biomecânicos , Humanos , Estresse Mecânico , Hemodinâmica/fisiologia , Óxido Nítrico/metabolismo , Mecanotransdução Celular/fisiologia , Vasos Sanguíneos/fisiologiaRESUMO
OBJECTIVE: Cardiovascular diseases, and the interventions performed to treat them, can lead to changes in the shape of patient vasculatures and their hemodynamics. Computational modeling and simulations of patient-specific vascular networks are increasingly used to quantify these hemodynamic changes, but they require modifying the shapes of the models. Existing methods to modify these shapes include editing 2D lumen contours prescribed along vessel centerlines and deforming meshes with geometry-based approaches. However, these methods can require extensive by-hand prescription of the desired shapes and often do not work robustly across a range of vascular anatomies. To overcome these limitations, we develop techniques to modify vascular models using physics-based principles that can automatically generate smooth deformations and readily apply them across different vascular anatomies. METHODS: We adapt Regularized Kelvinlets, analytical solutions to linear elastostatics, to perform elastic shape-editing of vascular models. The Kelvinlets are packaged into three methods that allow us to artificially create aneurysms, stenoses, and tortuosity. RESULTS: Our methods are able to generate such geometric changes across a wide range of vascular anatomies. We demonstrate their capabilities by creating sets of aneurysms, stenoses, and tortuosities with varying shapes and sizes on multiple patient-specific models. CONCLUSION: Our Kelvinlet-based deformers allow us to edit the shape of vascular models, regardless of their anatomical locations, and parametrically vary the size of the geometric changes. SIGNIFICANCE: These methods will enable researchers to more easily perform virtual-surgery-like deformations, computationally explore the impact of vascular shape on patient hemodynamics, and generate synthetic geometries for data-driven research.