RESUMO
OBJECTIVE: The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these 2 loci were subsequently confirmed in 3 independent cohorts (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (ßs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (ßs.d.=0.103; SE=0.015; P=4.66×10-12). Notably, the ACTN4/CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. CONCLUSIONS: Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.
Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Doenças Retinianas/genética , Vasos Retinianos/anormalidades , Vênulas/anormalidades , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Humanos , Fenótipo , Doenças Retinianas/complicações , Doenças Retinianas/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Fatores de RiscoRESUMO
OBJECTIVE: To describe typical clinical presentation of patients with microfistular, capillary-venule (CV) malformation as a variant form of arteriovenous malformations (AVM). METHODS: A retrospective clinical analysis of 15 patients with CV-AVM confirmed by a computational flow model enrolled in a prospective database of patients with congenital vascular malformation between January 2008 and May 2018. RESULTS: The mean age of the patients at first time of presentation was 30 years with balanced sex ratio. Presentation was dominated by soft tissue hypertrophy (n = 12 [80.0%]) and atypical varicose veins (n = 11 [73.3%]). The anatomic location of enlarged varicose veins gave no uniform pattern and did not correspond with the typical picture of primary varicose vein disease. Most often, symptomatic CV-AVM was found at the lower extremities in this series of unselected patients. The most frequent compartment affected was the subcutis (n = 14 [93.3%]), involvement of muscle was recorded in one-third and cutis in one-fourth of patients. CONCLUSIONS: A high grade of clinical suspicion is needed to recognize CV-AVM and to prevent inadequate therapy owing to missed diagnosis.
Assuntos
Malformações Arteriovenosas , Capilares/anormalidades , Vênulas/anormalidades , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/fisiopatologia , Malformações Arteriovenosas/terapia , Velocidade do Fluxo Sanguíneo , Capilares/diagnóstico por imagem , Capilares/fisiopatologia , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Úlcera da Perna/diagnóstico , Úlcera da Perna/etiologia , Úlcera da Perna/fisiopatologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Varizes/diagnóstico por imagem , Varizes/etiologia , Varizes/fisiopatologia , Vênulas/diagnóstico por imagem , Vênulas/fisiopatologia , Adulto JovemRESUMO
The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
Assuntos
Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/fisiologia , Linfocinas/genética , Linfocinas/fisiologia , Vasos Retinianos/crescimento & desenvolvimento , Animais , Arteríolas/anormalidades , Arteríolas/crescimento & desenvolvimento , Sequência de Bases , Padronização Corporal/genética , Padronização Corporal/fisiologia , DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Marcação de Genes , Masculino , Camundongos , Camundongos Transgênicos , Gravidez , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento do Endotélio Vascular , Vasos Retinianos/anormalidades , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Vênulas/anormalidades , Vênulas/crescimento & desenvolvimentoRESUMO
A 26-year-old man with a history of chronic primary lymphedema of the left lower extremity presented with elephantiasis, confluent, violaceous, mascerated plaques, and ulcers on the dorsal aspects of the toes of the left foot. Histopathologic examination showed a proliferation of small blood vessels associated with extravasated erythrocytes and hemosiderin deposits consistent with the diagnosis of acroangiodermatitis. Treatment of the focal ulcers includes compression therapy, local wound care, and surgical elimination of the shunt if there is an associated arteriovenous malformation.
Assuntos
Acrodermatite/complicações , Malformações Arteriovenosas/complicações , Pé/irrigação sanguínea , Acrodermatite/patologia , Adulto , Arteríolas/anormalidades , Malformações Arteriovenosas/patologia , Diagnóstico Diferencial , Humanos , Masculino , Vênulas/anormalidadesRESUMO
PURPOSE: To evaluate short-term efficacy of combining surgical ablation of retinal inflow and outflow vessels and photodynamic therapy (PDT) for stage 3 retinal angiomatous proliferation (RAP). DESIGN: Prospective interventional case series. METHODS: Five eyes (five patients) underwent surgical ablation of inflow and outflow vessels and PDT for stage 3 RAP. RESULTS: Inflow and outflow vessels were ablated in four eyes, and only inflow was ablated in one eye. In four eyes starting PDT within six weeks of surgical ablation, choroidal neovascularization (CNV) disappeared or shrank after one PDT session (three months follow-up). However, CNV enlarged again in three of the four (final follow-up) because of reperfusion from newly formed inflow vessels. In one eye starting PDT seven months after ablation, a new retinal inflow vessel feeding the CNV appeared by the time of the first PDT session. The CNV continued to expand, despite two PDT sessions. CONCLUSIONS: Combining surgical ablation and PDT was not useful on account of a high frequency of reperfusion from retinal inflow vessels.
Assuntos
Fístula Arteriovenosa/terapia , Corioide/irrigação sanguínea , Neovascularização de Coroide/terapia , Fotocoagulação a Laser , Fotoquimioterapia , Neovascularização Retiniana/terapia , Vasos Retinianos/anormalidades , Arteríolas/anormalidades , Fístula Arteriovenosa/tratamento farmacológico , Fístula Arteriovenosa/cirurgia , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/cirurgia , Terapia Combinada , Angiofluoresceinografia , Humanos , Verde de Indocianina , Estudos Prospectivos , Neovascularização Retiniana/tratamento farmacológico , Neovascularização Retiniana/cirurgia , Resultado do Tratamento , Vênulas/anormalidadesAssuntos
Angiografia Coronária , Vasos Coronários , Fístula/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico por imagem , Vênulas/anormalidades , Eletrocardiografia , Fístula/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/terapia , Miocárdio , Vênulas/diagnóstico por imagemRESUMO
We investigated the presence of twin vessels in two patients and in four of their relatives at risk from one family with autosomal-dominant hereditary cavernous hemangioma of the retina associated with central nervous system involvement. Twin vessels were detected in four of the six patients examined. The proband had bilateral retinal vascular hamartomas with central nervous system involvement but no twin vessels. The proband's mother had vascular hamartomas of the retina and brain with twin vessels. In the other three family members, twin vessels were associated either with retinal cavernous hemangiomas (one patient) or with normal fundi (two patients). Because twin vessels may be an ocular manifestation of von Hippel-Lindau disease, their presence in one of our two patients and in the otherwise healthy three family members suggests that twin vessels may be associated with different retinal vascular hamartomas, including capillary and cavernous hemangiomas.
Assuntos
Hemangioma Cavernoso/genética , Doenças Retinianas/genética , Vasos Retinianos/anormalidades , Adulto , Arteríolas/anormalidades , Criança , Feminino , Angiofluoresceinografia , Hamartoma/complicações , Hamartoma/genética , Hemangioma Cavernoso/complicações , Humanos , Masculino , Linhagem , Doenças Retinianas/complicações , Vênulas/anormalidades , Doença de von Hippel-Lindau/diagnósticoRESUMO
The syndrome of hemifacial spasm occurs as a consequence of compression, almost universally by blood vessels, of the root entry zone of the facial nerve. The vascular compression is usually obvious at operation, but may be subtle. The author describes a case in which a venule running in an anterior-posterior direction across the caudal aspect of the root entry zone of the facial nerve, which was thought to be causing the spasm, was coagulated and divided. A small, more distal arteriole, probably not contributory, was decompressed away from the nerve. After operation, the patient improved gradually, and she remains free of facial spasm or weakness. This is the most subtle vascular compression seen by the author and his colleagues in over 400 microvascular decompressions for hemifacial spasm.
Assuntos
Músculos Faciais/inervação , Doenças do Nervo Facial/complicações , Malformações Arteriovenosas Intracranianas/complicações , Síndromes de Compressão Nervosa/complicações , Espasmo/etiologia , Veias/anormalidades , Vênulas/anormalidades , Tronco Encefálico/irrigação sanguínea , Doenças do Nervo Facial/cirurgia , Feminino , Lateralidade Funcional , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/cirurgia , Vênulas/cirurgiaRESUMO
Although arteriovenous malformations (AVMs) have been known to have direct communications between arteries and veins without interposing capillaries, the exact location of arterial and venous junctions have not been defined. Utilizing microscopic and endoscopic observations, Yamada and associates identified shunting arterioles (50 mu-250 mu) directly connected to the AVM core vessels. While dissecting the AVMs in functional areas of the brain, shunting arterioles were sectioned to interrupt the arterial blood supply. This technique allowed cleavage formation between the core vessels and surrounding brain, thus avoiding brain tissue removal and preserving microcirculation to functionally critical brain. We demonstrate histologically for the first time by scanning electron microscopy shunting arterioles and communicating venules (20 mu-200 mu).
Assuntos
Artérias Cerebrais/anormalidades , Veias Cerebrais/anormalidades , Malformações Arteriovenosas Intracranianas/patologia , Microscopia Eletrônica de Varredura , Arteríolas/anormalidades , Arteríolas/patologia , Arteríolas/ultraestrutura , Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/ultraestrutura , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Vênulas/anormalidades , Vênulas/patologia , Vênulas/ultraestruturaRESUMO
PURPOSE: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. MATERIALS AND METHODS: A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. RESULTS: High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. CONCLUSIONS: High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities.
Assuntos
Vasos Sanguíneos/anormalidades , Vasos Sanguíneos/fisiopatologia , Líquido Extracelular/fisiologia , Melanoma/irrigação sanguínea , Pressão , Neoplasias Cutâneas/irrigação sanguínea , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Arteríolas/anormalidades , Arteríolas/patologia , Arteríolas/fisiopatologia , Vasos Sanguíneos/patologia , Linhagem Celular Tumoral , Feminino , Proteínas de Fluorescência Verde/metabolismo , Humanos , Melanoma/sangue , Melanoma/patologia , Melanoma/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/patologia , Fluxo Sanguíneo Regional , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia , Fatores de Tempo , Vênulas/anormalidades , Vênulas/patologia , Vênulas/fisiopatologiaRESUMO
Classification of cutaneous vascular anomalies is difficult because conceptual confusion persists between vascular neoplasms and malformations. However, hemangiomas of the infancy fulfill criteria both for hyperplasia and neoplasm because they result from proliferation of endothelial cells, but often undergo complete regression. Despite these pitfalls we have classified cutaneous vascular anomalies into the following categories: hamartomas, malformations, dilatations of preexisting vessels, hyperplasias, benign neoplasms, and malignant neoplasms. In this first part of our clinicopathologic review of vascular anomalies, hamartomas, malformations, and dilatation of preexisting vessels are covered. Hamartomas include several combined vascular and melanocytic proliferations grouped as phakomatosis pigmentovascularis and the so-called eccrine angiomatous hamartoma that consists of proliferations of both eccrine glands and blood vessels. Vascular malformations result from anomalies of embryologic development, and in some of them the abnormalities of the involved vessels are more functional than anatomic, as is the case of nevus anemicus. In contrast, other cutaneous vascular malformations show striking morphologic abnormalities of the vascular structures. These anatomic vascular malformations are subdivided into the following groups: capillary, venous, arterial, lymphatic, and combined anomalies. Spider angioma, capillary aneurysm-venous lake, and telangiectases are not vascular proliferations at all, but dilations of preexisting vessels. In our opinion, most of the lesions described with the generic term of "angiokeratoma" are not authentic vascular neoplasms, but hyperkeratotic malformations of capillaries and venules or acquired telangiectases of preexisting blood vessels of the papillary dermis. Therefore the first group of these "angiokeratomas" are included in the vascular malformations section, and the second group are covered in the section of dilation of preexisting vessels. Lymphangiectases are considered the lymphatic counterpart of angiokeratomas because they result from ectasia of preexisting lymphatic vessels of the papillary dermis.
Assuntos
Vasos Sanguíneos/anormalidades , Hamartoma/patologia , Dermatopatias Vasculares/patologia , Pele/irrigação sanguínea , Aneurisma/patologia , Angioceratoma/patologia , Capilares/anormalidades , Dilatação Patológica/patologia , Glândulas Écrinas/patologia , Endotélio Vascular/patologia , Hemangioma/patologia , Humanos , Hiperplasia , Lactente , Linfangiectasia/patologia , Sistema Linfático/anormalidades , Melanócitos/patologia , Regressão Neoplásica Espontânea , Remissão Espontânea , Telangiectasia/patologia , Neoplasias Vasculares/patologia , Vênulas/anormalidadesRESUMO
Las malformaciones vasculares son anomalías presentes siempre desde el nacimiento que, al contrario de los hemangiomas, nunca desaparecen; pueden crecer durante toda la vida por hipertrofia. Según la clasificación de la ISSVA, las malformaciones vasculares se dividen en función del vaso afectado en capilares o venulares, venosas, linfáticas, arterio-venosas y combinadas o complejas. Cada una de ellas, con unas peculiaridades clínicas y hemodinámicas definitorias.
Vascular malformations are anomalies always present at birth that, contrary to hemangiomas, never regress; and may hypertrophy during lifetime. According to the ISSVA classification, vascular malformations are divided, depending on the affected vessel, into capillary or venular, venous, lymphatic, arteriovenous and combined or complex; each with certain defining clinical and haemodynamic peculiarities.