原创力文档a local proinflammatory signalling loop facilitates adverse age-associated arterial remodeling当地的促炎信号循环促进不良与年龄有关的动脉重建.pdfVIP
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a local proinflammatory signalling loop facilitates adverse age-associated arterial remodeling当地的促炎信号循环促进不良与年龄有关的动脉重建
A Local Proinflammatory Signalling Loop Facilitates
Adverse Age-Associated Arterial Remodeling
1. 1,2. 1 1 1 1
Mingyi Wang *, Gaia Spinetti , Robert E. Monticone , Jing Zhang , James Wu , Liqun Jiang ,
1 1 1
Benjamin Khazan , Richard Telljohann , Edward G. Lakatta
1 Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America, 2 Casa di Cura,
MultiMedica-IRCCS, Milano, Italy
Abstract
Background: The coincidence of vascular smooth muscle cells (VSMC) infiltration and collagen deposition within a diffusely
thickened intima is a salient feature of central arterial wall inflammation that accompanies advancing age. However, the
molecular mechanisms involved remain undefined.
Methodology/Principal Findings: Immunostaining and immunoblotting of rat aortae demonstrate that a triad of
proinflammatory molecules, MCP-1, TGF-b1, and MMP-2 increases within the aortic wall with aging. Exposure of VSMC
isolated from 8-mo-old rats (young) to MCP-1 effects, via CCR-2 signaling, both an increase in TGF-b1 activity, up to levels of
untreated VSMC from 30-mo-old (old) rats, and a concurrent increase in MMP-2 activation. Furthermore, exposure of young
VSMC to TGF- b1 increases levels of MCP-1, and MMP-2 activation, to levels of untreated VSMC from old rats. This
autocatalytic signaling loop that enhances collagen production and invasiveness of VSMC is effectively suppressed by si-
MCP-1, a CCR2 antagonist, or MMP-2 inhibition.
Conclusions/Significance: Thresho
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