Dataset Information

Hyaluronidase-1 impairs endothelial barrier in a subtype of age-related macular degeneration

ABSTRACT: Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Here, we cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls. When BOECs were exposed to heterogeneous flow, single-cell analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of endothelial glycocalyx. Hyaluronidase-1 was correspondingly detected in PCV patient vitreous humor and plasma samples. Notably, knockdown of hyaluronidase-1 in PCV BOECs modulated their abnormal cell migration and barrier permeability due to glycocalyx impairment. Therefore, hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179631 | GEO | 2022/01/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Vascular endothelial and hematopoietic cells hold a close relationship that is initiated during development, but that continuously broadens to include new functions aimed at maintaining homeostasis in the adult organism. Here, we report on a population of aortic intimal resident macrophages (MacAIRs) that is a permanent feature of the inner vessel wall (tunica intima) of the aorta in regions of turbulent flow and that shares the luminal surface with the endothelium. MacAIRs were found to be transcriptionally distinct from other macrophages and closely associated with the endothelium in the absence of pathology. Lineage tracing analysis indicated that adult MacAIRs were derived from definitive hematopoietic lineage precursors that migrated from the ductus arteriosus seeding the aorta immediately post-birth in areas of turbulent flow including the lesser curvature of the aortic arch and branch openings. These aortic resident macrophages expanded via direct cell renewal and continued to grow in aged aortae to also populate regions of laminar flow. Binding of MacAIRs relied heavily on expression of endothelial ICAM that interacts with CD11c on macrophages. Genetic deletion of CD11c significantly impaired anchorage of MacAIRs to the endothelium. To clarify the biological significance of this population of macrophages, we used a dual diphtheria toxin induced-depletion system that efficiently eliminated MacAIRs in adult mice. Utilizing this model, we found that absence of MacAIRs led to progressive fibrin accumulation and formation of microclots that, once dislodged, can cause blockade of vessels and organ failure. In fact, 40% of the animals with genetic-mediated depletion of MacAIRs died within 2 weeks post-depletion suggesting that these macrophages were required to clear fibrin deposits in regions of turbulent blood flow. These findings advance our knowledge of how vascular endothelial cells profit from this unique interaction with macrophages to control hemostasis, prevent intravascular clotting, and ensure vascular health.

Dataset Information

Hyaluronidase-1 impairs endothelial barrier in a subtype of age-related macular degeneration

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets