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1.
Arterioscler Thromb Vasc Biol ; 42(9): e253-e272, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35924557

RESUMO

Evolutionary organization of the arterial wall into layers occurred concomitantly with the emergence of a highly muscularized, pressurized arterial system that facilitates outward hydraulic conductance and mass transport of soluble substances across the arterial wall. Although colliding circulating cells disperse potential energy within the arterial wall, the different layers counteract this effect: (1) the endothelium ensures a partial barrier function; (2) the media comprises smooth muscle cells capable of endocytosis/phagocytosis; (3) the outer adventitia and perivascular adipocytic tissue are the final receptacles of convected substances. While the endothelium forms a physical and a biochemical barrier, the medial layer is avascular, relying on the specific permeability properties of the endothelium for metabolic support. Different components of the media interact with convected molecules: medial smooth muscle cells take up numerous molecules via scavenger receptors and are capable of phagocytosis of macro/micro particles. The outer layers-the highly microvascularized innervated adventitia and perivascular adipose tissue-are also involved in the clearance functions of the media: the adventitia is the seat of immune response development, inward angiogenesis, macromolecular lymphatic drainage, and neuronal stimulation. Consequently, the clearance functions of the arterial wall are physiologically essential, but also may favor the development of arterial wall pathologies. This review describes how the walls of large conductance arteries have acquired physiological clearance functions, how this is determined by the attributes of the endothelial barrier, governed by endocytic and phagocytic capacities of smooth muscle cells, impacting adventitial functions, and the role of these clearance functions in arterial wall diseases.


Assuntos
Artérias , Doenças Vasculares , Tecido Adiposo , Túnica Adventícia/patologia , Artérias/patologia , Humanos , Miócitos de Músculo Liso/patologia , Doenças Vasculares/patologia
2.
Braz J Cardiovasc Surg ; 37(4): 439-446, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35976203

RESUMO

INTRODUCTION: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. METHODS: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. RESULTS: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P<0.05). After adventitial cross-linking, the collagen I fibres of the vein remarkably presented with compact and nonporous arrangement. In the high-stretch region (stretch ratio 1.4-1.8), the Young's elastic modulus of stress-stretch ratio curve in cross-linked SVs was larger than that in native SVs (13.88 vs. 5.83, P<0.05). The cross-linked SVs had a lower extent of endothelial denudation without fibre fracture during high-pressure distension than native SVs. Comparing with the non-cross-linked SVs, the percentage of endothelial nitric oxide synthase staining length on the endothelium of cross-linked SVs was significantly preserved after high-pressure distension (85.2% vs. 64.7%, P<0.05). CONCLUSION: Adventitial collagen cross-linking by glutaraldehyde reinforced venous wall by increasing stiffness and decreasing extensibility of SVs and mitigated the endothelial damage under high-pressure distension.


Assuntos
Túnica Adventícia , Veia Safena , Colágeno/metabolismo , Ponte de Artéria Coronária , Dilatação Patológica , Endotélio Vascular , Glutaral/farmacologia , Humanos , Veia Safena/transplante
4.
Theranostics ; 12(10): 4718-4733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832088

RESUMO

Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension. Methods: AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10 µM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs. Results: NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than ß-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation. Conclusion: NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.


Assuntos
Vesículas Extracelulares , Hipertensão , Túnica Adventícia/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Hipertensão/metabolismo , Músculo Liso Vascular/metabolismo , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Fentolamina/metabolismo , Fentolamina/farmacologia , Ratos , Ratos Endogâmicos WKY
5.
J Mech Behav Biomed Mater ; 134: 105371, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35868065

RESUMO

The trachea is a complex tissue made up of hyaline cartilage, fibrous tissue, and muscle fibers. Currently, the knowledge of microscopic structural organization of these components and their role in determining the tissue's mechanical response is very limited. The purpose of this study is to provide data on the microstructure of the tracheal components and its influence on tissue's mechanical response. Five bovine tracheae were used in this study. Adventitia, cartilage, mucosa/submucosa, and trachealis muscle layers were methodically cut out from the whole tissue. Second-harmonic generation(SHG) via multi-photon microscopy (MPM) enabled imaging of collagen fibers and muscle fibers. Simultaneously, a planar biaxial test rig was used to record the mechanical behavior of each layer. In total 60 samples were tested and analyzed. Fiber architecture in the adventitia and mucosa/submucosa layer showed high degree of anisotropy with the mean fiber angle varying from sample to sample. The trachealis muscle displayed neat layers of fibers organized in the longitudinal direction. The cartilage also displayed a structure of thick mesh-work of collagen type II organized predominantly towards the circumferential direction. Further, mechanical testing demonstrated the anisotropic nature of the tissue components. The cartilage was identified as the stiffest component for strain level < 20% and hence the primary load bearing component. The other three layers displayed a non-linear mechanical response which could be explained by the structure and organization of their fibers. This study is useful in enhancing the utilization of structurally motivated material models for predicting tracheal overall mechanical response.


Assuntos
Colágeno , Traqueia , Túnica Adventícia , Animais , Anisotropia , Bovinos , Colágeno/química , Estresse Mecânico , Suporte de Carga
6.
Acta Biomater ; 150: 295-309, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35905825

RESUMO

Coronary atherosclerosis is the main cause of death worldwide. Advancing the understanding of coronary microstructure-based mechanics is fundamental for the development of therapeutic tools and surgical procedures. Although the passive biaxial properties of the coronary arteries have been extensively explored, their regional differences and the relationship between tissue microstructure and mechanics have not been fully characterized. In this study, we characterized the passive biaxial mechanical properties and microstructural properties of the proximal, medial, and distal regions of the porcine left anterior descending artery (LADA). We also attempted to relate the biaxial stress-stretch response of the LADA and its respective birefringent responses to the polarized light for obtaining information about the load-dependent microstructural variations. We found that the LADA extensibility is reduced in the proximal-to-distal direction and that the medial region exhibits more heterogeneous mechanical behavior than the other two regions. We have also observed highly dynamic microstructural behavior where fiber families realign themselves depending on loading. In addition, we found that the microstructure of the distal region exhibited highly aligned fibers along the longitudinal axis of the artery. To verify this microstructural feature, we imaged the LADA specimens with multi-photon microscopy and observed that the adventitia microstructure transitioned from a random fiber network in the proximal region to highly aligned fibers in the distal region. Our findings could offer new perspectives for understanding coronary mechanics and aid in the development of tissue-engineered vascular grafts, which are currently limited due to their mismatch with native tissue in terms of mechanical properties and microstructural features. STATEMENT OF SIGNIFICANCE: The tissue biomechanics of coronary arteries is fundamental for the development of revascularization techniques such as coronary artery bypass. These therapeutics require a deep understanding of arterial mechanics, microstructure, and mechanobiology to prevent graft failure and reoperation. The present study characterizes the unique regional mechanical and microstructural properties of the porcine left anterior descending artery using biaxial testing, polarized-light imaging, and confocal microscopy. This comprehensive characterization provides an improved understanding of the collagen/elastin architecture in response to mechanical loads using a region-specific approach. The unique tissue properties obtained from this study will provide guidance for the selection of anastomotic sites in coronary artery bypass grafting and for the design of tissue-engineered vascular grafts.


Assuntos
Colágeno , Coração , Túnica Adventícia , Animais , Fenômenos Biomecânicos , Colágeno/química , Vasos Coronários/fisiologia , Estresse Mecânico , Suínos
7.
Artigo em Inglês | MEDLINE | ID: mdl-35758613

RESUMO

OBJECTIVES: The adventitial inversion technique is used widely for aortic reconstruction for acute type A aortic dissection, as it easily controls the bleeding at anastomotic sites and closes the patent false lumen. However, this technique for arch vessel reconstruction has not been previously reported. Therefore, we applied the adventitial inversion technique for dissected arch vessel reconstruction to close the patent false lumen. METHODS: Among 57 consecutive patients who underwent emergency surgical treatment for acute type A aortic dissection from July 2006 to July 2012, the adventitial inversion technique for the dissected arch vessels was performed in 26 patients (42 arch vessel stumps). The patency and morphologic change of the false lumen of the arch vessels were evaluated using contrast-enhanced computed tomography. RESULTS: Overall, 2 hospital deaths were recorded, and the hospital mortality rate was 4%. No postoperative cerebral strokes and reoperations due to bleeding occurred. Follow-up by contrast-enhanced computed tomography was completed in 24 patients (37 stumps) with a mean duration of 99 ± 35 months. The postoperative closure rate of the false lumen after adventitial inversion was 86%, which was higher than when adventitial inversion was not used. No adverse events including stroke occurred during follow-up period. CONCLUSIONS: This technique facilitates the closure of the false lumen of dissected arch vessels and might improve clinical outcomes.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Túnica Adventícia/diagnóstico por imagem , Túnica Adventícia/cirurgia , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos , Stents , Resultado do Tratamento
8.
J Biomech ; 141: 111174, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35701262

RESUMO

Aortic dissection is a life-threatening event, during which a primary tear propagates along the aorta causing catastrophic delamination of the inner (intima with most of the media) from the outer layers (leftover media with adventitia). Our understanding of mode-I fracture resistance at different aortic regions is incomplete, although the anatomical localization of the dissection channel may be assigned to this factor. To determine whether the susceptibility to dissection propagation varied with aortic region, the average and standard deviation of peel tension (indices of adhesive strength between layers when pulled apart and its fluctuation) were measured in 24 cadaveric subjects. Measurements were made in the inner and outer quadrants of 9 consecutive regions. Strong regional heterogeneity was established that was age-related based on the following evidence: (1) the average and standard deviation of peel tension peaked in the ascending aorta, decreasing to almost constant values in the descending thoracic aorta, but increasing across the abdominal aorta; (2) axial differences were more pronounced in the inner quadrant, with differences among quadrants reaching significance proximally; (3) the average peel tension was greatly impaired from <40 to 40-60 but much less to >60-year-old subjects at most regions/quadrants, leading to non-uniform axial variations in all age groups; (4) gender affected little the data. This comprehensive series of delamination tests explains the clinical observation of most dissections initiating in the ascending aorta to extend distally and of few dissections initiating in the descending thoracic aorta to extend proximally, while supporting the increased vulnerability in aged subjects.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Túnica Adventícia , Idoso , Aorta Abdominal , Aorta Torácica , Humanos , Pessoa de Meia-Idade
9.
J Biomech ; 138: 111133, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35569429

RESUMO

Aortic dissection often initiates a few centimeters distal to the coronary ostia in the right lateral wall, with an intimal-medial tear that tends to be transversely directed and occupy half of the aortic circumference, sometimes less, but seldom the entire circumference. To elucidate these clinical observations, tear tests were presently used to determine the layer-specific resistance to tear propagation in ascending thoracic aortic aneurysms, assessing variations over the four circumferential quadrants and two directions. Aneurysmal tissue strips of standardized dimensions from sixteen patients were anatomically separated into layers (seven hundred and twelve) and an incision made along one-third of their length. They underwent tear testing via uniaxial loading and then unloading before crack propagation had proceeded along their complete length. The average tear tension and tear energy per reference area generated were many-fold greater in outer- (adventitial) compared to inner- (intimal with small medial portion) and middle-layer (medial) strips, explaining why the tear is restricted to the inner wall. They were greater in inner- compared to middle-layer strips of the anterior and left lateral quadrants, suggesting that the tear will propagate to the less-resistant media even if initiated in the intima. In most longitudinally-cut middle- and inner-layer strips, the cracks deviated toward the circumferential direction and tore out through the side, justifying the circumferential course of the tear. Both fracture parameters were significantly higher in the right than the left lateral quadrant in outer-layer strips and the anterior quadrant in middle-layer strips, potentially affecting the circumferential extent of the tear.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Túnica Adventícia , Aorta , Fenômenos Biomecânicos , Humanos
10.
Sci Rep ; 12(1): 8632, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606390

RESUMO

The media of aortic wall is characterized by altering layers of elastin and smooth muscle cells (SMCs), along with collagen fibers in both layers, and plays a central role in functional and pathological remodeling such as hypertension and atherosclerosis. Because the arterial function is linked closely to the arterial wall internal structure, it is essential to investigate the alteration of the arterial microstructure during macroscopic deformation to understand cardiovascular pathologies. The present study adopted a tissue clearing method in three-dimensional mechanical characterization of rat thoracic aorta, and successfully observed changes in the structure of each of the three primary components of the aorta under intraluminal pressurization while maintaining tissue mechanical integrity and flexibility. Layers of elastic fibers and SMCs deformed greater on the intimal side than those on the adventitial side. Furthermore, there was a structural agreement in the alignment angle between SMC nuclei and elastic fibers on their intimal side, but not on the adventitial side. This is the first study that changes in the microstructure of three primary components of the aorta were visualized and evaluated through the aorta. The method established here would also be useful to understand tissue mechanics of other load-bearing soft tissues.


Assuntos
Aorta Torácica , Aorta , Túnica Adventícia , Animais , Aorta/patologia , Núcleo Celular , Elastina , Miócitos de Músculo Liso , Ratos , Estresse Mecânico
11.
Diab Vasc Dis Res ; 19(3): 14791641221094321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35637577

RESUMO

Obesity is linked to increased arterial size, carotid intima-media thickness and arterial stiffness. The effects of obesity and body composition on muscular artery intima-media and adventitia thickness has previously not been established. The aim of this study was to explore associations between carotid and muscular artery wall layer thickness with body composition and cardiovascular risk factors in early middle-aged women. This is a cross-sectional study including 199 women aged 40±4 years. Arterial lumen (LD), intima-media (IMT) and adventitia thickness (AT) were measured from carotid, brachial and radial arteries using ultra-high frequency ultrasound (22-71 MHz). Women with obesity had increased IMT in carotid (0.47 vs 0.45 mm), brachial (0.19 vs 0.17 mm) and radial arteries (0.16 vs 0.15 mm) and increased brachial AT (0.14 vs 0.13 mm). In multiple regression models all arterial LD (ß-range 0.02-0.03 mm/kg/m2), IMT (ß-range 0.91-3.37 µm/kg/m2), AT (ß-range 0.73-1.38 µm/kg/m2) were significantly associated with BMI. The IMT of all arteries were significantly associated with systolic blood pressure (ß-range 0.36-0.85 µm/mmHg), attenuating the association between IMT and BMI (ß-range 0.18-2.24 µm/kg/m2). Obese early middle-aged women have increased arterial intima media thickness and brachial artery adventitia thickness compared to non-obese counterparts. The association between BMI and intima-media thickness is partly mediated through blood pressure levels.


Assuntos
Túnica Adventícia , Espessura Intima-Media Carotídea , Túnica Adventícia/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Fatores de Risco
12.
Acta Biomater ; 146: 248-258, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35526737

RESUMO

Abdominal aortic aneurysms (AAAs) are a dangerous cardiovascular disease, the pathogenesis of which is not yet fully understood. In the present work a recent mechanopathological theory, which correlates AAA progression with microstructural and mechanical alterations in the tissue, is investigated using multiscale models. The goal is to combine these changes, within the framework of mechanobiology, with possible mechanical cues that are sensed by vascular cells along the AAA pathogenesis. Particular attention is paid to the formation of a 'neo-adventitia' on the abluminal side of the aortic wall, which is characterized by a highly random (isotropic) distribution of collagen fibers. Macro- and micro-scale results suggest that the formation of an AAA, as expected, perturbs the micromechanical state of the aortic tissue and triggers a growth and remodeling (G&R) reaction by mechanosensing cells such as fibroblasts. This G&R then leads to the formation of a thick neo-adventitia that appears to bring the micromechanical state of the tissue closer to the original homeostatic level. In this context, this new layer could act like a protective sheath, similar to the tunica adventitia in healthy aortas. This potential 'attempt at healing' by vascular cells would have important implications on the stability of the AAA wall and thus on the risk of rupture. STATEMENT OF SIGNIFICANCE: Current clinical criteria for risk assessment in AAAs are still empirical, as the causes and mechanisms of the disease are not yet fully understood. The strength of the arterial tissue is closely related to its microstructure, which in turn is remodeled by mechanosensing cells in the course of the disease. In this study, multiscale simulations show a possible connection between mechanical cues at the microscopic level and collagen G&R in AAA tissue. It should be emphasized that these micromechanical cues cannot be visualized in vivo. Therefore, the results presented here will help to advance our current understanding of the disease and motivate future experimental studies, with important implications for AAA risk assessment.


Assuntos
Aneurisma da Aorta Abdominal , Túnica Adventícia/patologia , Aorta , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/patologia , Colágeno , Humanos
13.
Methods Mol Biol ; 2475: 229-238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35451762

RESUMO

The ex vivo aortic ring assay is one of the most widely used protocols to study sprouting angiogenesis. It is a highly adaptable method that can be utilized to investigate the effects of different growth factors, small-molecule drugs, and genetic modifications on vascular sprouting in a physiologically relevant setting. In this chapter we describe a simple and optimized protocol for investigating vascular sprouting in the mouse aortic ring model. The protocol describes the harvesting and embedding of the aortic rings in a collagen matrix, treatment of the rings with agents of interest, and the visualization and quantification of the vascular sprouts.


Assuntos
Vasos Linfáticos , Neovascularização Fisiológica , Túnica Adventícia , Animais , Aorta , Camundongos , Neovascularização Patológica , Neovascularização Fisiológica/fisiologia
14.
Methods Mol Biol ; 2419: 611-627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237992

RESUMO

Aging is associated with alterations in the arterial wall that promote vascular disease development and its clinical manifestations, including myocardial infarction, stroke, and arterial dissection. The arterial wall is comprised of three layers, intima, media and adventitia, each with distinct cellular composition and function, which can therefore contribute differently to vascular disease initiation and progression. Hence, studying transcriptomic alterations, either in the entire arterial wall or separately in the three arterial layers, can aid in disentangling the etiopathology of vascular disease and thus pave the way for innovative treatments. This chapter describes protocols for total RNA extraction from complete mouse aorta and separately from intima, media, and adventitia layers for subsequent transcriptomic analysis.


Assuntos
RNA , Transcriptoma , Túnica Adventícia , Animais , Aorta/patologia , Artérias , Camundongos
15.
Methods Mol Biol ; 2419: 809-823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35238003

RESUMO

Atheromatous lesions are characterized by intrusion into the vascular lumen, resulting in morphological changes to the blood compartment and into the vessel wall, resulting in characteristic molecular and cellular signatures in the solid tissue of the intima, tunica media, adventitia and surrounding tissue. Nanoprobes can be easily formulated to provide long blood-pool residence and molecular targeting, facilitating the imaging of atheromatous changes. Detection of nanoprobes can be accomplished by a variety of methods. We focus in this chapter on the use of cross-sectional imaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI), that facilitate in vivo, noninvasive imaging of the vascular morphology and molecular/cellular signatures of the atheroma. The methods described are suitable for use in animal models, although versions of the probes are being readied for clinical trials, potentially facilitating clinical use in the future.


Assuntos
Aterosclerose , Placa Aterosclerótica , Túnica Adventícia/patologia , Animais , Aterosclerose/patologia , Imageamento por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagem , Tomografia Computadorizada por Raios X
16.
Cell Death Dis ; 13(3): 220, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264563

RESUMO

Pathological angiogenesis promotes tumor growth, metastasis, and atherosclerotic plaque rupture. Macrophages are key players in these processes. However, whether these macrophages differentiate from bone marrow-derived monocytes or from local vascular wall-resident stem and progenitor cells (VW-SCs) is an unresolved issue of angiogenesis. To answer this question, we analyzed vascular sprouting and alterations in aortic cell populations in mouse aortic ring assays (ARA). ARA culture leads to the generation of large numbers of macrophages, especially within the aortic adventitia. Using immunohistochemical fate-mapping and genetic in vivo-labeling approaches we show that 60% of these macrophages differentiate from bone marrow-independent Ly6c+/Sca-1+ adventitial progenitor cells. Analysis of the NCX-/- mouse model that genetically lacks embryonic circulation and yolk sac perfusion indicates that at least some of those progenitor cells arise yolk sac-independent. Macrophages represent the main source of VEGF in ARA that vice versa promotes the generation of additional macrophages thereby creating a pro-angiogenetic feedforward loop. Additionally, macrophage-derived VEGF activates CD34+ progenitor cells within the adventitial vasculogenic zone to differentiate into CD31+ endothelial cells. Consequently, depletion of macrophages and VEGFR2 antagonism drastically reduce vascular sprouting activity in ARA. In summary, we show that angiogenic activation induces differentiation of macrophages from bone marrow-derived as well as from bone marrow-independent VW-SCs. The latter ones are at least partially yolk sac-independent, too. Those VW-SC-derived macrophages critically contribute to angiogenesis, making them an attractive target to interfere with pathological angiogenesis in cancer and atherosclerosis as well as with regenerative angiogenesis in ischemic cardiovascular disorders.


Assuntos
Túnica Adventícia , Células Endoteliais , Túnica Adventícia/patologia , Animais , Medula Óssea/patologia , Células Endoteliais/patologia , Macrófagos/patologia , Camundongos , Neovascularização Patológica/patologia , Células-Tronco/patologia , Fator A de Crescimento do Endotélio Vascular
18.
Gene ; 819: 146233, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35121027

RESUMO

BACKGROUND: Due to permanent aortic dilation, thoracic aortic aneurysm (TAA) is a life-threatening disease. Once ruptured, TAA has a high lethality and disability rate. Although studies have focused on transcriptomic alterations in TAA, more detailed analysis is still lacking, especially the different aortic intima-media and adventitia roles. This study aimed to identify the different co-expression patterns between the aortic intima-media and the adventitia underlying the aortic dilation. METHODS: We analyzed the gene expression profiles obtained from Gene Expression Omnibus (GEO, GSE26155) database. With a false discovery rate (FDR) < 0.05 and |log2FC| ≥ 1, 56 and 33 differential genes in the intima-media and adventitia, respectively, between the non-dilated and dilated status. Gene ontology (GO) and gene set enrichment analysis revealed that degranulation and activation of neutrophils play an essential role in the intima-media of dilated aortas. Through weighted gene co-expression network analysis (WGCNA), we identified essential co-expressed modules and hub genes to explore the biological functions of the dysregulated genes. RESULTS: Functional pathway analysis suggested that lipid metabolism, C-C motif chemokine pathways were significantly enriched in the adventitia, whereas ribosome proteins and related mRNA translation pathways were closely related to intima and media. Furthermore, the ssGSEA analysis indicated that macrophages, helper T cells, and neutrophils were higher in the intima-media of the dilated thoracic aorta. Finally, we validated the critical findings of the study with the murine model of TAA. CONCLUSION: This study identified and verified hub genes and pathways in aortic intima-media and adventitia prominently associated with aortic dilation, providing practical understanding in the perspective of searching for new molecular targets.


Assuntos
Túnica Adventícia/metabolismo , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/metabolismo , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Transcriptoma , Túnica Íntima/metabolismo , Animais , Quimiocinas/metabolismo , Dilatação Patológica/genética , Dilatação Patológica/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação , Metabolismo dos Lipídeos , RNA Mensageiro/metabolismo , Proteínas Ribossômicas/metabolismo
19.
Biochem Biophys Res Commun ; 594: 38-45, 2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-35066378

RESUMO

Recent studies have emphasized the role of vascular adventitia inflammation and immune response in hypertension. It has been reported that stromal cell-derived factor-1 (SDF-1) plays various biological functions through its receptors C-X-C motif chemokine receptor 4 (CXCR4) and CXCR7 in tumor growth and tissue repair. However, it is unclear that whether SDF-1/CXCR4/CXCR7 axis is involved in hypertensive vascular remodeling. In the present study, the involvement of SDF-1/CXCR4/CXCR7 axis was evaluated with lentivirus-mediated shRNA of SDF-1 and CXCR7, CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207 in angiotensin II (AngII)-induced hypertensive mice and in cultured adventitial fibroblasts (AFs). Results showed that AngII infusion markedly increased SDF-1 expressed in vascular adventitia, but not in media and endothelium. Importantly, blockade of SDF-1/CXCR4 axis strikingly potentiated AngII-induced adventitial thickening and fibrosis, as indicated by enhanced collagen I deposition. In contrast, CXCR7 shRNA largely attenuated AngII-induced adventitial thickness and fibrosis, whereas CXCR7 activation with VUF11207 significantly potentiated AngII-induced adventitial thickening and fibrosis. In consistent with these in vivo study, CXCR4 inhibition with AMD3100 and CXCR7 activation with VUF11207 aggravated AngII-induced inflammation, proliferation and migration in cultured AFs. In summary, these results suggested that SDF-1 exerted opposing effects through CXCR4 and CXCR7 in AngII-induced vascular adventitial remodeling.


Assuntos
Túnica Adventícia/metabolismo , Angiotensina II/metabolismo , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Animais , Benzilaminas/farmacologia , Movimento Celular/fisiologia , Proliferação de Células , Colágeno/metabolismo , Ciclamos/farmacologia , Modelos Animais de Doenças , Fibroblastos/patologia , Fibrose , Hipertensão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Cicatrização
20.
J Biomech ; 132: 110909, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032837

RESUMO

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results. The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.


Assuntos
Túnica Adventícia , Aorta Abdominal , Túnica Adventícia/fisiologia , Animais , Anisotropia , Fenômenos Biomecânicos , Estresse Mecânico , Suínos
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