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The vasa vasorum of the large pulmonary vessels is involved in the pathology of COVID-19. This specialized microvasculature plays a major role in the biology and pathology of the pulmonary vessel walls. We have evidence that thrombosis of the vasa vasorum of the large and medium-sized pulmonary vessels during severe COVID-19 causes ischemia and subsequent death of the pulmonary vasculature endothelium. Subsequent release of thrombi from the vasa interna into the pulmonary circulation and pulmonary embolism generated at the ischemic pulmonary vascular endothelium site, are the central pathophysiological mechanisms in COVID-19 responsible for pulmonary thromboembolism. The thrombosis of the vasa vasorum of the large and medium-sized pulmonary vessels is an internal event leading to pulmonary thromboembolism in COVID-19.

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ABSTRACT The vasa vasorum of the large pulmonary vessels is involved in the pathology of COVID-19. This specialized microvasculature plays a major role in the biology and pathology of the pulmonary vessel walls. We have evidence that thrombosis of the vasa vasorum of the large and medium-sized pulmonary vessels during severe COVID-19 causes ischemia and subsequent death of the pulmonary vasculature endothelium. Subsequent release of thrombi from the vasa interna into the pulmonary circulation and pulmonary embolism generated at the ischemic pulmonary vascular endothelium site, are the central pathophysiological mechanisms in COVID-19 responsible for pulmonary thromboembolism. The thrombosis of the vasa vasorum of the large and medium-sized pulmonary vessels is an internal event leading to pulmonary thromboembolism in COVID-19.

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This short article discusses selected scanning electron microscope and transmission electron microscope features of vasa vasorum including pericytes and basement membrane of the human saphenous vein (SV) harvested with either conventional (CON) or no-touch (NT) technique for coronary artery bypass grafting. Scanning electron microscope data shows the general damage to vasa vasorum of CON-SV, while the transmission electron microscope data presents ultrastructural features of the vasa in more detail. Hence there are some features suggesting pericyte involvement in the contraction of vasa blood vessels, particularly in CON-SV. Other features associated with the vasa vasorum of both CON-SV and NT-SV preparations include thickened and/or multiplied layers of the basement membrane. In some cases, multiple layers of basement membrane embrace both pericyte and vasa microvessel making an impression of a "unit" made by basement membrane-pericyte-endothelium/microvessel. It can be speculated that this structural arrangement has an effect on the contractile and/or relaxing properties of the vessels involved. Endothelial colocalization of immunoreactive inducible nitric oxide synthase and endothelin-1 can be observed (with laser confocal microscope) in some of the vasa microvessels. It can be speculated that this phenomenon, particularly of the expression of inducible nitric oxide synthase, might be related to structurally changed vasa vessels, e.g., with expanded basement membrane. Fine physiological relationships between vasa vasorum endothelium, basement membrane, pericyte, and perivascular nerves have yet to be uncovered in the detail needed for better understanding of the cells'specific effects in SV preparations for coronary artery bypass grafting.

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ABSTRACT This short article discusses selected scanning electron microscope and transmission electron microscope features of vasa vasorum including pericytes and basement membrane of the human saphenous vein (SV) harvested with either conventional (CON) or no-touch (NT) technique for coronary artery bypass grafting. Scanning electron microscope data shows the general damage to vasa vasorum of CON-SV, while the transmission electron microscope data presents ultrastructural features of the vasa in more detail. Hence there are some features suggesting pericyte involvement in the contraction of vasa blood vessels, particularly in CON-SV. Other features associated with the vasa vasorum of both CON-SV and NT-SV preparations include thickened and/or multiplied layers of the basement membrane. In some cases, multiple layers of basement membrane embrace both pericyte and vasa microvessel making an impression of a "unit" made by basement membrane-pericyte-endothelium/microvessel. It can be speculated that this structural arrangement has an effect on the contractile and/or relaxing properties of the vessels involved. Endothelial colocalization of immunoreactive inducible nitric oxide synthase and endothelin-1 can be observed (with laser confocal microscope) in some of the vasa microvessels. It can be speculated that this phenomenon, particularly of the expression of inducible nitric oxide synthase, might be related to structurally changed vasa vessels, e.g., with expanded basement membrane. Fine physiological relationships between vasa vasorum endothelium, basement membrane, pericyte, and perivascular nerves have yet to be uncovered in the detail needed for better understanding of the cells'specific effects in SV preparations for coronary artery bypass grafting.

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Abstract The importance of the vasa vasorum and blood supply to the wall of human saphenous vein (hSV) used for coronary artery bypass grafting (CABG) is briefly discussed. This is in the context of the possible physical link of the vasa vasorum connecting with the lumen of hSV and the anti-ischaemic impact of this microvessel network in the hSV used for CABG.

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The importance of the vasa vasorum and blood supply to the wall of human saphenous vein (hSV) used for coronary artery bypass grafting (CABG) is briefly discussed. This is in the context of the possible physical link of the vasa vasorum connecting with the lumen of hSV and the anti-ischaemic impact of this microvessel network in the hSV used for CABG.

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Perivascular adipose tissue (PVAT) is a source of factors affecting vasomotor tone with the potential to play a role in the performance of saphenous vein (SV) bypass grafts. As these factors have been described as having constrictor or relaxant effects, they may be considered either beneficial or detrimental. The close proximity of PVAT to the adventitia provides an environment whereby adipose tissue-derived factors may affect the vasa vasorum, a microvascular network providing the vessel wall with oxygen and nutrients. Since medial ischaemia promotes aspects of graft occlusion the involvement of the PVAT/vasa vasorum axis in vein graft patency should be considered.

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Abstract Perivascular adipose tissue (PVAT) is a source of factors affecting vasomotor tone with the potential to play a role in the performance of saphenous vein (SV) bypass grafts. As these factors have been described as having constrictor or relaxant effects, they may be considered either beneficial or detrimental. The close proximity of PVAT to the adventitia provides an environment whereby adipose tissue-derived factors may affect the vasa vasorum, a microvascular network providing the vessel wall with oxygen and nutrients. Since medial ischaemia promotes aspects of graft occlusion the involvement of the PVAT/vasa vasorum axis in vein graft patency should be considered.

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BACKGROUND: Anti-angiogenic regulators may have therapeutic implications for onset and progression of atherosclerosis. OBJECTIVES: To demonstrate histological changes secondary to the use of bevacizumab in the aorta of pigs after interruption of flow in the vasa vasorum. METHODS: Twelve pigs were divided into two groups. The intercostal arteries of the descending aorta were dissected and ligated and wrapped with a polyvinyl chloride membrane. The treatment group received an intravenous dose of bevacizumab. After 15 days, the animals were euthanized and the aorta removed. Histological slides were prepared for control and treatment groups and for non-manipulated areas and analyzed for degree of angiogenesis, injury, inflammation, and intimal thickening. Data were expressed as mean (SD) of scores and groups were compared using the Mann-Whitney test. The Poisson distribution was used to calculate 95% confidence intervals for mean scores, in order to determine effect statistics. RESULTS: Bevacizumab had adverse effects on all treated pigs. The analysis using a Scale of Magnitudes for Effect Statistics showed a trend toward a decrease in angiogenesis [0.58 (1.79/-0.63)] and injury [0.55 (1.76/-0.66)] and an increase in inflammation [0.67 (1.89/-0.55)] with threshold moderate effects. There was no difference in intimal thickening [0 (1.19/-1.19)]. CONCLUSIONS: The medication exhibited a trend toward reduced angiogenesis and injury, but no reduction in the inflammatory process or intimal thickening of the aortic wall. These findings are in disagreement with studies that correlate neovascularization with increased migration of inflammatory cells. Bevacizumab exhibited toxicity in the porcine model.

CONTEXTO: Agentes antiangiogênicos podem ter implicações terapêuticas na progressão e manifestação da aterosclerose. OBJETIVOS: Demonstrar a alteração histológica secundária ao uso de bevacizumabe na aorta descendente de suínos submetida à interrupção dos vasa vasorum. MÉTODOS: Em doze suínos, divididos em dois grupos, foi realizada dissecção da aorta torácica, além de ligadura das artérias intercostais e proteção com polivinil. O grupo tratamento recebeu dose endovenosa de bevacizumabe. Após 15 dias, os animais foram sacrificados para retirada da artéria e preparo das lâminas histológicas dos grupos tratamento, controle e áreas não manipuladas para análise quanto aos graus de angiogênese, injúria, inflamação e espessamento intimal. A análise estatística foi conduzida através da média e do desvio padrão dos escores. As comparações entre os grupos foram realizadas pelo teste de Mann-Whitney. A distribuição de Poisson calculou os intervalos de confiança de 95% para as médias, a fim de determinar o efeito estatístico. RESULTADOS: O bevacizumabe causou efeitos adversos em todos os suínos tratados. As variáveis analisadas através da Escala de Magnitude para Efeito Estatístico demonstraram tendência de redução da angiogênese [0,58 (1,79/-0,63)] e da injúria [0,55 (1,76/-0,66)] e aumento da inflamação [0,67 (1,89/-0,55)] no limite do moderado. Não ocorreu diferença no espessamento intimal [0 (1,19/-1,19)]. CONCLUSÕES: A medicação utilizada mostrou tendência de redução da angiogênese e da injúria, mas não reduziu o processo inflamatório ou o espessamento intimal da parede arterial. Esses achados contrariam estudos que correlacionam a neovascularização com o aumento da migração de células inflamatórias. O bevacizumabe mostrou toxicidade no modelo suíno.

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Background Anti-angiogenic regulators may have therapeutic implications for onset and progression of atherosclerosis. Objectives To demonstrate histological changes secondary to the use of bevacizumab in the aorta of pigs after interruption of flow in the vasa vasorum. Methods Twelve pigs were divided into two groups. The intercostal arteries of the descending aorta were dissected and ligated and wrapped with a polyvinyl chloride membrane. The treatment group received an intravenous dose of bevacizumab. After 15 days, the animals were euthanized and the aorta removed. Histological slides were prepared for control and treatment groups and for non-manipulated areas and analyzed for degree of angiogenesis, injury, inflammation, and intimal thickening. Data were expressed as mean (SD) of scores and groups were compared using the Mann-Whitney test. The Poisson distribution was used to calculate 95% confidence intervals for mean scores, in order to determine effect statistics. Results Bevacizumab had adverse effects on all treated pigs. The analysis using a Scale of Magnitudes for Effect Statistics showed a trend toward a decrease in angiogenesis [0.58 (1.79/-0.63)] and injury [0.55 (1.76/-0.66)] and an increase in inflammation [0.67 (1.89/-0.55)] with threshold moderate effects. There was no difference in intimal thickening [0 (1.19/-1.19)]. Conclusions The medication exhibited a trend toward reduced angiogenesis and injury, but no reduction in the inflammatory process or intimal thickening of the aortic wall. These findings are in disagreement with studies that correlate neovascularization with increased migration of inflammatory cells. Bevacizumab exhibited toxicity in the porcine model

Agentes antiangiogênicos podem ter implicações terapêuticas na progressão e manifestação da aterosclerose. Objetivos Demonstrar a alteração histológica secundária ao uso de bevacizumabe na aorta descendente de suínos submetida à interrupção dos vasa vasorum. Métodos Em doze suínos, divididos em dois grupos, foi realizada dissecção da aorta torácica, além de ligadura das artérias intercostais e proteção com polivinil. O grupo tratamento recebeu dose endovenosa de bevacizumabe. Após 15 dias, os animais foram sacrificados para retirada da artéria e preparo das lâminas histológicas dos grupos tratamento, controle e áreas não manipuladas para análise quanto aos graus de angiogênese, injúria, inflamação e espessamento intimal. A análise estatística foi conduzida através da média e do desvio padrão dos escores. As comparações entre os grupos foram realizadas pelo teste de Mann-Whitney. A distribuição de Poisson calculou os intervalos de confiança de 95% para as médias, a fim de determinar o efeito estatístico. Resultados O bevacizumabe causou efeitos adversos em todos os suínos tratados. As variáveis analisadas através da Escala de Magnitude para Efeito Estatístico demonstraram tendência de redução da angiogênese [0,58 (1,79/-0,63)] e da injúria [0,55 (1,76/-0,66)] e aumento da inflamação [0,67 (1,89/-0,55)] no limite do moderado. Não ocorreu diferença no espessamento intimal [0 (1,19/-1,19)]. Conclusões A medicação utilizada mostrou tendência de redução da angiogênese e da injúria, mas não reduziu o processo inflamatório ou o espessamento intimal da parede arterial. Esses achados contrariam estudos que correlacionam a neovascularização com o aumento da migração de células inflamatórias. O bevacizumabe mostrou toxicidade no modelo suíno

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Actualmente se acepta que la adventicia tiene: un importante rol fisiológico al determinar el nivel de nutrición, oxigenación, reparación arterial, regulación de la vasomotricidad, control de la poscarga ventricular, control de la función arterial, etcétera, a la vez que tiene una importante participación en procesos patológicos (por ejemplo, aterosclerosis, hipertensión arterial, génesis de aneurismas de aorta abdominal). Sin embargo, dado lo reciente de la mayoría de los estudios que han redefinido el rol de la adventicia, aún persiste mucho desconocimiento en la comunidad biomédica acerca de la fisiología de la capa adventicia arterial. El presente trabajo tiene como objetivo revisar el rol que actualmente se reconoce para la capa adventicia de la pared arterial.

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OBJETIVO: Investigar os efeitos da remoção da adventícia da aorta em suínos. MÉTODOS: O experimento foi realizado com oito suínos. Removeu-se a camada adventícia da aorta descendente. Após a eutanásia com duas, quatro, seis e oito semanas, o segmento aórtico era removido. Após, eram feitos cortes histológicos com a coloração de hematoxilina e eosina (HE) e pelo método de Weigert - Van Gieson. RESULTADOS: Após duas semanas identificou-se um leve desarranjo do terço externo da túnica média. Nos animais sacrificados após quatro semanas observou-se um desarranjo estrutural dos terços externos da túnica média. Após seis semanas observou-se necrose da parede aórtica. Finalmente, após oito semanas além da fibrose da parede aórtica identificou-se a destruição da lâmina elástica interna. CONCLUSÃO: A remoção da adventícia da aorta em suínos levou à alterações degenerativas da média, determinando perda da estrutura da parede aórtica que é variável em sua localização, intensidade e forma, dependendo do tempo a partir do qual se estabeleceu a lesão isquêmica.

OBJECTIVE: To investigate the effects of removal of the adventitia on the tunica media in a pig model. METHODS: The experiment was performed in eight pigs. The adventitia of the descending aorta was removed. Following euthanasia, at two, four, six and eight weeks, the aortic segment was removed. Next, slices of the aorta were stained with hematoxylin and eosin (HE) and Weigert - Van Gieson. RESULTS: After two weeks there was a slight cellular breakdown in the outer third of the media. After four weeks structural breakdown of elastic fibers was observed in the outer two thirds of the same layer. In six weeks, several areas of necrosis and almost complete disruption of elastic fibers were identified. Finally, after eight weeks, there was fibrosis of the entire wall with disruption of the internal elastic lamina. CONCLUSION: The removal of the adventitia leads to degeneration of the media, determining loss of the normal structure of the aortic wall that is variable in its location, intensity and shape, depending on the length and duration of the ischemic insult.

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A ruptura dos vasa vasorum tem sido reconhecida como uma das causas do hematoma intramural da aorta há 90 anos. Esta breve revisão apresenta sistematicamente a fisiologia desses vasos e o seu papel na fisiopatologia das alterações parietais da aorta que ocorrem na hipertensão arterial, na arteriosclerose e na síndrome aórtica aguda. A hipótese defendida aqui é a de que a ruptura dos vasa vasorum ocorre como um fenômeno secundário e não como um dos fatores causais na fisiopatologia do hematoma intramural.

Rupture of vasa varorum has been recognized as one cause of intramural hematoma of the aorta for 90 years. This brief revision presents systematically, the physiology of these vessels and its role in the physiopathology of the alterations in the aortic wall secondary to hypertension, arteriosclerosis and in Acute Aortic Syndrome. The hypothesis is that rupture of vasa vasorum is a secondary phenomenon and not one causal factor in the physiopathology of intramural hematoma.

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La adventicia se ha definido como la capa de tejido conectivo más externa de un vaso y no formaría una unidad con la estructura vascular. El término "adventicia" proviene del latín adventicius, que significa "venido de afuera, extraño". Estos conceptos tal vez constituyan la causa de la subestimación del papel fisiológico de esta túnica. Al presente es bien conocido que la adventicia contiene vasa vasorum y nervi vasorum con funciones nutricionales y de control, respectivamente. A ello se suma la presencia de factores bioquímicos que serían responsables de cambios en la conducta elástica y viscosa de la pared arterial a través de una regulación de la función muscular lisa. En este trabajo se realiza una síntesis del papel estructural y fisiológico de la adventicia; se analizan además datos clínicos y experimentales que se comparan con resultados originales publicados por el autor.

The adventitia has been defined as the outermost connective tissue covering of a vessel, and does not form an integral part of the vascular structure. The term "adventitia" comes from the Latin word adventicius, meaning "coming from abroad, foreign". These concepts may explain why the physiological role of this tunic has been underestimated. It is well known that the adventitia has vasa vasorum and nervi vasorum with nutritional and control functions, respectively. In addition, biochemical factors may probably account for changes seen in elastic and viscous behaviour of the arterial wall due to changes in smooth muscle function. This study reports a summary of the structural and physiological role of the adventitia: clinical and experimental data are also analyzed and compared with the original outcomes published by the author.