Matrix sieving-enforced retrograde transcytosis regulates tissue accumulation of C-reactive protein.

Abstract:

Aims:Circulating proteins larger than 3 nm can be transported across continuous endothelial barrier of blood vessels via transcytosis. However, excessive accumulation of serum proteins within the vessel walls is uncommon even for those abundant in the circulation. The aim of this study was to investigate how transcytosis regulates tissue accumulation of the prototypical acute-phase reactant C-reactive protein (CRP) and other serum proteins. Methods and results:Transcytosis of CRP as well as of transferrin and low-density lipoprotein across aortic endothelial cells is bidirectional with directional preference from the apical (blood) to basolateral (tissue) direction both in vitro and in vivo. This directional preference is, however, reversed by the basement membrane (BM) matrix underlying the basolateral surface of endothelial cells. This is due to the sieving effect of the BM that physically hinders the diffusion of transcytosed proteins from the apical compartment towards underlying tissues, resulting in immediate retrograde transcytosis that limits basolateral protein accumulation. Conversely, CRP produced within vessel wall lesions can also be transported into the circulation. Conclusion:Our findings identify matrix sieving-enforced retrograde transcytosis as a general mechanism that prevents excessive tissue accumulation of blood-borne proteins and suggest that lesion-derived CRP might also contribute to elevated serum CRP levels associated with increased risk for cardiovascular diseases.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Li HY,Liu XL,Liu YT,Jia ZK,Filep JG,Potempa LA,Ji SR,Wu Y

doi

10.1093/cvr/cvy181

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

440-452

issue

2

eissn

0008-6363

issn

1755-3245

pii

5050858

journal_volume

115

pub_type

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