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Osteoprotegerin Prevents Intracranial Aneurysm Progression by Promoting Collagen Biosynthesis and Vascular Smooth Muscle Cell Proliferation

Miyata, Takeshi 京都大学 DOI:10.14989/doctor.k23380

2021.05.24

概要

BACKGROUND: Decreased extracellular matrix formation and few vascular smooth muscle cells (VSMCs) in cerebral vascular walls are the main characteristics of intracranial aneurysm (IA) pathogenesis. Recently, osteoprotegerin was reported to activate collagen biosynthesis and VSMC proliferation via the TGF-β1 (transforming growth factor-β1) signaling. This study aimed to investigate whether osteoprotegerin can prevent IA progression in rats through enhanced collagen expression and VSMC proliferation.

METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague–Dawley rats; at 1-week post-operation, recombinant mouse osteoprotegerin or vehicle control was continuously infused for 4 weeks into the lateral ventricle using an osmotic pump. In the osteoprotegerin-treatment group, the aneurysmal size was significantly smaller (37.5 μm versus 60.0 μm; P

CONCLUSIONS: Osteoprotegerin suppressed the IA progression by a unique mechanism whereby collagen biosynthesis and VSMC proliferation were activated via TGF-β1 without altering proinflammatory gene expression. Osteoprotegerin may represent a novel therapeutic target for IAs.

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