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Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE-/- mouse model of atherosclerosis. Methods Aortic specimens were carefully excised from the ApoE-/- mouse model. Following immunostaining with specific antibodies against smooth muscle actin (SMA) and lymphatic vessel endothelial receptor 1 (LYVE1), the aortas, including the aortic root, were subjected to a 30-minute treatment with 5 g/L Sudan Black B solution. This step was instrumental in minimizing the autofluorescent background of the tissue. Thereafter, the aortas were processed through a clearing protocol and imaged within a purpose-built chamber under a fluorescence microscope. Results The pretreatment with 5 g/L Sudan Black B effectively suppressed the autofluorescent signals emanating from the vascular structures, thereby enhancing the contrast and clarity of the specific fluorescence signals associated with the lymphatic vessels. This enhancement in signal quality did not compromise the integrity or specificity of the immunofluorescent markers. Conclusion A facile, highly specific, and effective approach for the visualization of lymphatic vessels in whole-mount aortic preparations from ApoE-/- mice is established.
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Aorta , Apolipoproteínas E , Técnica del Anticuerpo Fluorescente , Vasos Linfáticos , Animales , Vasos Linfáticos/metabolismo , Vasos Linfáticos/diagnóstico por imagen , Ratones , Aorta/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/deficiencia , Apolipoproteínas E/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Adventicia/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Coloración y Etiquetado/métodos , Microscopía Fluorescente/métodosRESUMEN
Introduction: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the world's population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis. Material and methods: This cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery. Results: Results revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density. Conclusion: These findings suggest that NASH severity doesn't independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.
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Grosor Intima-Media Carotídeo , Enfermedad del Hígado Graso no Alcohólico , Índice de Severidad de la Enfermedad , Vasa Vasorum , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Vasa Vasorum/patología , Estudios Transversales , Persona de Mediana Edad , Adulto , Adventicia/patología , Aterosclerosis/patología , Obesidad/patología , Obesidad/complicacionesRESUMEN
OBJECTIVE: It was previously believed that atherosclerotic (AS) plaque starts to develop from the intima and that intraplaque vasa vasorum (VV) hyperplasia promotes adventitial VV (AVV) hyperplasia. However, recent studies have shown that arterial AVV hyperplasia precedes early intimal thickening, suggesting its possible role as an initiating factor of AS. To provide further insight into this process, in this study, we examine the evolution of AAV and VV development in a preclinical model of early AS with longitudinal ultrasound imaging. METHODS: Models of early AS were established. Duplex ultrasound scanning and contrast-enhanced ultrasound were performed for diagnosis. Pearson correlation tests were used to analyze the relationships between AVV hyperplasia and VV hyperplasia, or between AVV hyperplasia and intima-media thickness (IMT). RESULTS: During 0-12 wk of high-fat feeding, AVV gradually increased and intima-media thickened gradually in the observation area; in the 2nd wk of high-fat feeding, the observation area showed obvious AVV proliferation; at the 4th wk, the intima-media membrane became thicker; at the 12th wk, early plaque formation and intraplaque VV proliferation were observed. There was a strong positive correlation between AVV proliferation and IMT thickening and a strong negative correlation between AVV proliferation and the change rate of vessel diameter. CONCLUSION: This study demonstrated that AVV proliferation in the arteries occurred earlier than IMT thickening and was positively correlated with IMT. At present, the indicators of ultrasonic diagnosis of AS, such as IMT, Intraplaque VV, Echo property, all appear in the advanced stage of AS. The AVV may be an innovative diagnostic target for the early stage of AS plaque.
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Modelos Animales de Enfermedad , Hiperplasia , Placa Aterosclerótica , Vasa Vasorum , Animales , Vasa Vasorum/diagnóstico por imagen , Vasa Vasorum/patología , Placa Aterosclerótica/diagnóstico por imagen , Conejos , Hiperplasia/diagnóstico por imagen , Masculino , Adventicia/diagnóstico por imagen , Adventicia/patología , Ultrasonografía/métodosRESUMEN
INTRODUCTION: Cystic adventitial disease (CAD) is an uncommon condition that affects arteries and veins. It can cause a rare type of non-atherosclerotic peripheral vessel disease. The most common vessel affected is the popliteal artery. The number of case reports on CAD of the femoral artery is growing. We present a case of a 62-year-old female presented with claudication of the left leg diagnosed with CAD of the left common femoral artery. The patient was treated surgically with cyst excision and vessel reconstruction with saphenous vein autograft patch plasty. After 8-months the cyste relapsed and she had new claudication complains. We decided to perform new surgery. Surgical treatment consisted of cyst resection by excision of the femoral bifurcation and saphenous vein autograft interposition reconstruction of the bifurcation. We also provide an update on the latest literature of surgical treatment of CAD of the ilio-femoral artery region. METHODS: Medline and EMBASE were used to collect articles on CAD of ilio-femoral artery. We included English written or translated case reports or series between 1987 and 2023. RESULTS: Twenty-nine patients out of 28 case reports were included. Most patients were male (59%). Claudication is the most common symptom (76%). Treatment consisted of cyst resection, cyst decompression, Endarterectomy, patch angioplasty and interposition graft using PTFE, Dacron, Great saphenous vein (GSV) or femoral vein autograft. Recurrence appeared in 4 cases (14%). CONCLUSION: In accordance to the literature and our experience we recommend complete vessel excision and saphenous vein (or PTFE) interposition bypass as treatment.
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Adventicia , Quistes , Arteria Femoral , Vena Safena , Humanos , Femenino , Arteria Femoral/cirugía , Persona de Mediana Edad , Quistes/cirugía , Adventicia/cirugía , Vena Safena/trasplante , Claudicación Intermitente/etiología , Claudicación Intermitente/cirugíaRESUMEN
Collagen fiber arrangement is decisive for constitutive description of anisotropic mechanical response of arterial wall. In this study, their orientation in human common carotid artery was investigated using polarized light microscopy and an automated algorithm giving more than 4·106 fiber angles per slice. In total 113 slices acquired from 18 arteries taken from 14 cadavers were used for fiber orientation in the circumferential-axial plane. All histograms were approximated with unimodal von Mises distribution to evaluate dominant direction of fibers and their concentration parameter. 10 specimens were analyzed also in circumferential-radial and axial-radial planes (2-4 slices per specimen in each plane); the portion of radially oriented fibers was found insignificant. In the circumferential-axial plane, most specimens showed a pronounced unimodal distribution with angle to circumferential direction µ = 0.7° ± 9.4° and concentration parameter b = 3.4 ± 1.9. Suitability of the unimodal fit was confirmed by high values of coefficient of determination (mean R2 = 0.97, median R2 = 0.99). Differences between media and adventitia layers were not found statistically significant. The results are directly applicable as structural parameters in the GOH constitutive model of arterial wall if the postulated two fiber families are unified into one with circumferential orientation.
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Arterias Carótidas , Matriz Extracelular , Humanos , Arterias Carótidas/fisiología , Adventicia , Algoritmos , Estrés Mecánico , Fenómenos Biomecánicos , Colágeno/químicaRESUMEN
The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.
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Aorta Torácica , Disección Aórtica , Homeostasis , Microscopía Electrónica de Transmisión , Telocitos , Humanos , Telocitos/patología , Telocitos/metabolismo , Telocitos/ultraestructura , Disección Aórtica/patología , Disección Aórtica/fisiopatología , Disección Aórtica/metabolismo , Aorta Torácica/patología , Aorta Torácica/metabolismo , Masculino , Persona de Mediana Edad , Anciano , Adventicia/patología , Adventicia/metabolismo , Aneurisma de la Aorta Torácica/patología , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/fisiopatología , Femenino , Telopodos/patología , Telopodos/metabolismo , Adulto , Técnica del Anticuerpo Fluorescente , Estudios de Casos y ControlesRESUMEN
Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.
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Adventicia , Aneurisma de la Aorta Abdominal , Humanos , Adventicia/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Macrófagos/metabolismo , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismoRESUMEN
TECHNIQUE: The reinforcement of the suture lines in acute type A aortic dissection include the treatment of proximal and distal anastomoses. The intima of the proximal site is transected circumferentially, approximately 1.0 cm above the sinotubular junction. The adventitia is folded outwards along the cutting edge of the intima, and the eversion forms an overlap. An autologous pericardial strip is placed inside the aorta as a mattress and secured with 4-0 prolene running sutures to the adventitial eversion overlap to reinforce the proximal cuff without any glue.The distal aortic cuff is trimmed and retained at 1.5 cm longer than the stent graft.The autologous pericardial strip is placed between the aortic intima and the stent graft and secured with 4-0 prolene running sutures to the adventitial eversion overlap to reinforce the distal cuff and completely obliterate the distal false lumen. RESULTS: The modified sandwich technique using adventitial eversion combined with an autologous pericardial strip achieved complete hemostasis at the anastomosis site and effectively obliterated the false lumen of the proximal and distal aorta. CONCLUSIONS: The adventitial valgus technique combined with autologous pericardial strip reinforcement can be inexpensive and effective for the surgical treatment of acute type A aortic dissection, especially in patients with fragile aortic wall.
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Disección Aórtica , Implantación de Prótesis Vascular , Humanos , Adventicia/cirugía , Polipropilenos , Implantación de Prótesis Vascular/métodos , Disección Aórtica/cirugía , Aorta Torácica/cirugía , Resultado del Tratamiento , Técnicas de SuturaRESUMEN
The histology of blood vessels shows they are structured in three layers or tunics: tunica intima, which includes the internal limiting lamina with high elastin content; tunica media of smooth muscles fibers of circular disposition, which includes the external limiting lamina; and tunica adventitia of connective tissue. The vascular system is essential in regulating body temperature, especially in the scrotum and testis. This study aimed to analyze the histology of the scrotal arteries and their possible relationship to testicular temperature homeostasis. This study used scrotal samples from human adults, anonymized and obtained from the University of Chile's teaching bank. The control group corresponds to an arteriole of muscle tissue. The results show that the middle layer of the scrotal artery is made up of smooth muscle fibers distributed in two layers: a longitudinal inner sublayer and a circular outer sublayer, different from the findings in muscle tissue arteries, with a single, circularly arranged muscle layer. This arrangement could be related to testicular temperature homeostasis by reducing the temperature of the testis and seminiferous tubules. The results described in this work suggest that these anatomical adaptations may be very significant in the face of the constant increase in global temperature. Further and better research is required to understand the mechanisms of thermoregulation in human reproduction and the histological particularities of the tissues that form the scrotum. RESEARCH HIGHLIGHTS: The human scrotal artery has a histological composition adapted for regulation of testicular temperature. The muscular double middle layer of the scrotal artery retains intravascular temperature.
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Adventicia , Escroto , Masculino , Adulto , Humanos , Escroto/fisiología , Biodiversidad , Temperatura , Testículo/fisiología , Arterias/fisiología , Regulación de la Temperatura Corporal/fisiologíaRESUMEN
A reform in the diagnosis and treatment process is urgently required as carotid artery disease remains a leading cause of death in the world. To this purpose, all computational techniques are now being applied to enhancing the most cutting-edge diagnosis techniques. Computational modeling of plaque generation and evolution is being refined over the past years to forecast the atherosclerotic progression and the corresponding risk in patient-specific carotid arteries. A prerequisite to their implementation is the reconstruction of the precise three-dimensional models of patient-specific main carotid arteries. Even with the most sophisticated algorithms, accurate reconstruction of the arterial vessel is frequently difficult. Furthermore, there are several works of plaque growth modeling that ignore the reconstruction of the artery's outer layer in favor of a virtual one. In this paper, we investigate the importance of an accurate adventitia layer in plaque growth modeling. This is done as a comparative study by implementing a novel plaque growth model in two reconstructed carotid arterial segments using either their realistic or virtual adventitia layer as input. The results indicate that accurate adventitia reconstruction is of minor importance regarding species distributions and plaque growth in carotid segments, which initially did not contain any plaque regions.Clinical Relevance- The findings of this comparative study emphasize the importance of precise adventitia geometry in plaque growth modeling. As a result, this work sets a higher standard for publishing new plaque growth models.
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Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico , Adventicia , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Simulación por ComputadorRESUMEN
OBJECTIVE: To evaluate the efficacy of three jaw adventitia holding (TADH) microclamps in end-to-end microvascular anastomosis. BACKGROUND: Acland clamps, though highly efficacious, require a steep learning curve and are associated with complications such as back walling and incomplete bites. METHODS: A single center, parallel group, 30-patient randomized clinical trial was conducted with a 1:1 allocation ratio in Acland and TADH microclamp groups. Primary outcome was time taken for microvascular anastomosis in terms of arterial and venous clamping and suturing time. Secondary outcomes included ease of use, need for clamp flipping and adventitia trimming, and need for assistance and flap survival. RESULTS: TADH microclamps were found to be beneficial when compared to Acland microclamps in end-to-end microvascular anastomosis, in terms of artery clamp time (19.07 ± 3.751 min, 95% CI 10.058-17.942, p < 0.001), artery suture time (15.87 ± 3.357 min, 95% CI 10.660-17.206, p < 0.001), vein clamp time (21.50 ± 3.849 min, 95% CI 12.131-19.469, p < 0.001), and vein suture time (16.58 ± 3.147 min, 95% CI 13.232-20.368, p < 0.001). The TADH microclamps did not require flipping to enable suturing of the posterior walls of the vessel. Statistically significant difference was found in surgeon-reported ease of use with TADH microclamps (Chi-square value 9.867, p < 0.001). Statistically significant difference was found in relation to the need for assistance with TADH microclamps (Chi-square value 19.286, p < 0.001). CONCLUSION: This study found TADH microclamps to be faster, easier to use, and clinically efficacious in reducing the anastomosis time compared to those of the Acland clamps.
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Adventicia , Microcirugia , Humanos , Colgajos Quirúrgicos/irrigación sanguínea , Arterias , Anastomosis Quirúrgica , Técnicas de SuturaRESUMEN
Intraperitoneal sporadic tumor is a common and complicated syndrome in cancers, causing a high rate of death, and people find that intraperitoneal chemotherapy (IPC) can treat intraperitoneal sporadic tumors better than intravenous chemotherapy and surgery. However, the effectiveness and side effects of IPC are controversial, and the operation process of IPC is complicated. Herein, the injectable paclitaxel-loaded (PTX-loaded) electrospun short fibers are constructed through a series process of electrospinning, homogenizing, crosslinking, and subsequent polydopamine coating and folate acid (FA) modification. The evenly dispersed short fibers exhibited effective tumor cell killing and good injectable ability, which is convenient to use and greatly improved the complex operation procedure. Mussel-like protein poly-dopamine coating and FA modification endowed short fibers with the ability of targeted adhesion to tumors, and therefore the short fibers further acted as a kind of micro membrane that could release drugs to tumors at close range, maintaining local high drug concentration and prevent paclitaxel killing normal tissues. Thus, the target-adhesive injectable electrospun short fibers are expected to be the potential candidate for cancer treatment, especially the intraperitoneal sporadic tumors, which are hard to treat by surgery or intravenous chemotherapy.
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Adventicia , Neoplasias , Humanos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Proteínas , PerfusiónRESUMEN
Tissue engineering has driven significant research in the strive to create a supply of tissues for patient treatment. Cell integration into engineered tissues maximizes functional capabilities, however, issues of rejection remain. Autologous cell sources able to solve this issue are difficult to identify for tissue engineering purposes. Here, we present the efficacy of patient-sourced cells derived from adipose (adipose-derived stem cells, ASCs) and skin tissue (dermal fibroblasts, PtFibs) to build a combined engineered tunica media and adventitia graft, respectively. Patient cells were integrated into our lab's vascular tissue engineering technique of forming vascular rings that are stacked into a tubular structure to create the vascular graft. For the media layer, ASCs were successfully differentiated into the smooth muscle phenotype using angiotensin II followed by culture in smooth muscle growth factors, evidenced by significantly increased expression of αSMA and myosin light chain kinase. Engineered media vessels composed of differentiated ASCs (ASC-SMCs) exhibited an elastic modulus (45.2 ± 18.9 kPa) between that of vessels of undifferentiated ASCs (71.8 ± 35.3 kPa) and control human aortic smooth muscle cells (HASMCs; 18.7 ± 5.49 kPa) (p<0.5). Tensile strength of vessels composed of ASCs (41.3 ± 15.7 kPa) and ASC-SMCs (37.3 ± 17.0 kPa) were higher compared to vessels of HASMCs (28.4 ± 11.2 kPa). ASC-based tissues exhibited a significant increase in collagen content and fiber maturity- both factors contribute to tissue strength and stability. Furthermore, vessels gained stability and a more-uniform single-tubular shape with longer-term 1-month culture. This work demonstrates efficacy of ASCs and PtFibs to create patient-specific vessels.
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Adventicia , Túnica Media , Humanos , Aorta , Colágeno , Células MadreRESUMEN
BACKGROUND: For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy. METHODS: We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia. RESULTS: After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P = .002) and impaired long-term survival (P < .001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group. CONCLUSIONS: After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Adventicia , Metástasis Linfática , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , ChinaRESUMEN
Open vascular reconstructions such as bypass are common treatments for cardiovascular disease. Unfortunately, neointimal hyperplasia (IH) follows, leading to treatment failure for which there is no approved therapy. Here we combined the strengths of tailoring nanoplatforms for open vascular reconstructions and targeting new epigenetic mechanisms. We produced adhesive nanoparticles (ahNP) that could be pen-brushed and immobilized on the adventitia to sustainably release pinometostat, an inhibitor drug selective to the epigenetic writer DOT1L that catalyzes histone-3 lysine-79 dimethylation (H3K79me2). This treatment not only reduced IH by 76.8% in injured arteries mimicking open reconstructions in obese Zucker rats with human-like diseases but also avoided the shortcoming of endothelial impairment in IH management. In mechanistic studies, chromatin immunoprecipitation (ChIP) sequencing revealed co-enrichment of the histone mark H3K27ac(acetyl) and its reader BRD4 at the gene of aurora kinase B (AURKB), where H3K79me2 was also enriched as indicated by ChIP-qPCR. Accordingly, DOT1L co-immunoprecipitated with H3K27ac. Furthermore, the known IH driver BRD4 governed the expression of DOT1L which controlled AURKB's protein level, revealing a BRD4- > DOT1L- > AURKB axis. Consistently, AURKB-selective inhibition reduced IH. Thus, this study presents a prototype nanoformulation suited for open vascular reconstructions, and the new insights into chromatin modulators may aid future translational advances.
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Adventicia , Proteínas Nucleares , Ratas , Animales , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Adventicia/metabolismo , Neointima/tratamiento farmacológico , Factores de Transcripción/metabolismo , Ratas Zucker , Epigénesis Genética , Endotelio , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Proteínas de Ciclo Celular/genéticaRESUMEN
Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular disease. A stereotypical vascular injury response is ECM (extracellular matrix) remodeling that occurs particularly in larger vessels in response to injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory cell infiltration, or exposure to proinflammatory mediators. Even with substantial and prolonged vascular damage, large- and medium-sized arteries, persist, but become modified by (1) changes in vascular wall cellularity; (2) modifications in the differentiation status of endothelial cells, vascular smooth muscle cells, or adventitial stem cells (each can become activated); (3) infiltration of the vascular wall by various leukocyte types; (4) increased exposure to critical growth factors and proinflammatory mediators; and (5) marked changes in the vascular ECM, that remodels from a homeostatic, prodifferentiation ECM environment to matrices that instead promote tissue reparative responses. This latter ECM presents previously hidden matricryptic sites that bind integrins to signal vascular cells and infiltrating leukocytes (in coordination with other mediators) to proliferate, invade, secrete ECM-degrading proteinases, and deposit injury-induced matrices (predisposing to vessel wall fibrosis). In contrast, in response to similar stimuli, capillaries can undergo regression responses (rarefaction). In summary, we have described the molecular events controlling ECM remodeling in major vascular diseases as well as the differential responses of arteries versus capillaries to key mediators inducing vascular injury.
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Enfermedades Vasculares , Lesiones del Sistema Vascular , Humanos , Células Endoteliales , Lesiones del Sistema Vascular/metabolismo , Matriz Extracelular/metabolismo , Adventicia , Enfermedades Vasculares/metabolismo , Remodelación VascularRESUMEN
The vasa vasorum (vessels of vessels) are a dynamic microvascular system uniquely distributed to maintain physiological homeostasis of the artery wall by supplying nutrients and oxygen to the outer layers of the artery wall, adventitia, and perivascular adipose tissue, and in large arteries, to the outer portion of the medial layer. Vasa vasorum endothelium and contractile mural cells regulate direct access of bioactive cells and factors present in both the systemic circulation and the arterial perivascular adipose tissue and adventitia to the artery wall. Experimental and human data show that proatherogenic factors and cells gain direct access to the artery wall via the vasa vasorum and may initiate, promote, and destabilize the plaque. Activation and growth of vasa vasorum occur in all blood vessel layers primarily by angiogenesis, producing fragile and permeable new microvessels that may cause plaque hemorrhage and fibrous cap rupture. Ironically, invasive therapies, such as angioplasty and coronary artery bypass grafting, injure the vasa vasorum, leading to treatment failures. The vasa vasorum function both as a master integrator of arterial homeostasis and, once perturbed or injured, as a promotor of atherogenesis. Future studies need to be directed at establishing reliable in vivo and in vitro models to investigate the cellular and molecular regulation of the function and dysfunction of the arterial vasa vasorum.
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Aterosclerosis , Vasa Vasorum , Humanos , Arterias , Adventicia , MicrovasosRESUMEN
OBJECTIVE: To study of nerve structures in the aortic wall in atherosclerosis using a complex of immunohistochemical markers. MATERIAL AND METHODS: The objects of the study were excised fragments of the wall of the thoracic and abdominal aorta along with visually determined unstable atherosclerotic plaques. To study nerve structures on paraffin sections, immunohistochemical reactions were performed for the PGP 9.5 protein, tyrosine hydroxylase, and synaptophysin. RESULTS: It has been established that pronounced pathological changes are observed in the nervous structures of the aortic wall near unstable atherosclerotic plaques. Reactive, dystrophic, and severe degenerative changes in neurocytes, nerve fibers, and glial cells are described in the elements of the nervous apparatus of the adventitia (microganglia, nerve trunks, and nerve plexuses). It was found that only sympathetic neurons and their postganglionic fibers remain in the intramural ganglia, while the structures of the parasympathetic nervous apparatus undergo degeneration. Destruction of perivascular nerve plexuses and vasa vasorum in the adventitia, as well as degeneration of varicose axons of the main terminal synaptic plexus at the border of adventitia and superficial smooth muscle layer of the media were demonstrated. CONCLUSION: It is assumed that the presence of inflammatory infiltrates in the adventitia and intima, denervation and death of vasa vasorum can serve as factors determining the development of the atherosclerotic process.