THSD1 preserves vascular integrity and protects against intraplaque haemorrhaging in ApoE-/- mice

Cardiovascular Research
Remco A HaasdijkHenricus J Duckers

Abstract

Impairment of the endothelial barrier leads to microvascular breakdown in cardiovascular disease and is involved in intraplaque haemorrhaging and the progression of advanced atherosclerotic lesions that are vulnerable to rupture. The exact mechanism that regulates vascular integrity requires further definition. Using a microarray screen for angiogenesis-associated genes during murine embryogenesis, we identified thrombospondin type I domain 1 (THSD1) as a new putative angiopotent factor with unknown biological function. We sought to characterize the role of THSD1 in endothelial cells during vascular development and cardiovascular disease. Functional knockdown of Thsd1 in zebrafish embryos and in a murine retina vascularization model induced severe haemorrhaging without affecting neovascular growth. In human carotid endarterectomy specimens, THSD1 expression by endothelial cells was detected in advanced atherosclerotic lesions with intraplaque haemorrhaging, but was absent in stable lesions, implying involvement of THSD1 in neovascular bleeding. In vitro, stimulation with pro-atherogenic factors (3% O2 and TNFα) decreased THSD1 expression in human endothelial cells, whereas stimulation with an anti-atherogenic factor (IL10) show...Continue Reading

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Citations

Nov 27, 2018·Cardiovascular Research·Heather Y Small, Tomasz J Guzik
May 6, 2019·Neuromolecular Medicine·Zhen XuDong H Kim
Aug 18, 2021·Stroke; a Journal of Cerebral Circulation·Mark K Bakker, Ynte M Ruigrok

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