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Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish.

ABSTRACT: The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO-induced vascular relaxation, which led to blood perfusion into the lymphatic system. NO blockage almost completely abrogated hypoxia-induced ALC relaxation and lymphatic perfusion. These findings uncover mechanisms underlying hypoxia-induced oxygen compensation by perfusion of existing lymphatics in fish. Our results might also imply that the hypoxia-induced NO pathway contributes to development of progression of pathologies, including promotion of lymphatic metastasis by modulating arterial-lymphatic conduits, in the mammalian system.

SUBMITTER: Dahl Ejby Jensen L

PROVIDER: S-EPMC2775321 | biostudies-other | 2009 Oct

REPOSITORIES: biostudies-other

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Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish.

Dahl Ejby Jensen Lasse L Cao Renhai R Hedlund Eva-Maria EM Söll Iris I Lundberg Jon O JO Hauptmann Giselbert G Steffensen John Fleng JF Cao Yihai Y

Proceedings of the National Academy of Sciences of the United States of America 20091012 43

The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxi ...[more]

PMID: 19822749

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Project description:PurposeTranscatheter arterial embolization or transcatheter arterial chemoembolization has become a critical therapy for unresectable hepatocarcinoma. Although hypoxia caused by embolization can induce apoptosis and necrosis of the majority of tumor cells, a small proportion of cells can survive with hypoxia and chemotherapy resistance. HIF-1α induced by hypoxia is the key factor rendering surviving tumor cells invasive and metastatic properties. Thus, we generated a synthetic hypoxia-replicative oncolytic adenovirus (HYAD) expecting to further eliminate the surviving tumor cells, which expressed HIF-1α.Materials and methodsIn our study, we detected protein expression, proliferation, apoptosis, and necrosis of hepatic tumor cell line when infected with HYAD under hypoxia and normoxia. And we constructed VX2 hepatic cancer rabbit models to explore the therapeutic effect of transcatheter arterial embolization combined with HYAD perfusion under digital subtraction angiography. Inhibition of tumor growth and invasion was detected by histopathological examination and contrast-enhanced CT scan.ResultsExperiments in vitro verified that HYAD expressed and replicated along with HIF-1α expression or hypoxia. Compared with wild adenovirus type 5 (WT), HYAD expressed much more under hypoxia, which was the main principle of HYAD killing surviving tumor cells posttransarterial embolization. In vivo experiment of VX2 models, HYAD perfusion combined with polyvinyl alcohol (PVA) embolization achieved the highest expression quantity and the longest expression duration compared with simple HYAD perfusion, WT perfusion combined with PVA embolization, and simple WT perfusion. Because adenovirus expression protein E1A had the properties of promoting apoptosis, inhibiting invasion, and inhibiting metastasis, HYAD perfusion combined with PVA embolization group efficiently repressed tumor growth and intrahepatic metastases compared to other processing groups.ConclusionHYAD can overcome the hypoxic tumor microenvironment postembolization and target the surviving tumor cells with specificity. In turn, HYAD perfusion combined with PVA embolization can bring out the best effect in each other.

Dataset Information

Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish.

Publications

Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish.

Similar Datasets

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