Aging reprograms the arterial wall via proinflammation signals partially mediated by matrix metalloproteinases type II (MMP-2) activation;however, whether inactivation of MMP-2 could slow the arterial aging process remain undefined. This study shows that a triad of arterial proinflammatory molecules, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factorVbeta 1 (TGFbetawzn and MMP-2 nconverging p-SMAD2/3 signaling and common transcription factor Ets-1n increases in FXBN rats with aging. Interestingly, 16-month-old rats treated daily with the MMP inhibitor (MMPI), PD166793 (5mg/kg) for 8 mo substantially inhibited arterial MMP-2 activation and attenuated an age-associated increase in systolic blood pressure(SBP), intima thickness (IT), media thickness (MT), MCP-1, TGF- beta1, p-SMAD2/3, and levels of ets-1 and collagen I . Further, in vitro studies show that exposure of young VSMC to MCP-1 via its receptor, CCR-2 signaling, increase TGF- beta1 and MMP-2 activity, and conversely, exposure of young VSMC to TGF- beta1 increases levels of MCP-1, and MMP-2 activation, both to levels of untreated old cells. Collagen deposition and VSMC invasion capacity resulting from this autocatalytic signaling triad are effectively reduced by a neutralizing MMP-2 antibody. Thus, inactivation of MMP2, a breaker of local proinflammation loop signaling, could be a novel approach to the prevention of arterial aging.
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| Wang, Mingyi; Monticone, Robert E; McGraw, Kimberly R (2018) Proinflammatory Arterial Stiffness Syndrome: A Signature of Large Arterial Aging. J Vasc Res 55:210-223 |
| Zhu, Wanqu; Kim, Byoung Choul; Wang, Mingyi et al. (2018) TGF?1 reinforces arterial aging in the vascular smooth muscle cell through a long-range regulation of the cytoskeletal stiffness. Sci Rep 8:2668 |
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| Wang, Mingyi; Jiang, Liqun; Monticone, Robert E et al. (2014) Proinflammation: the key to arterial aging. Trends Endocrinol Metab 25:72-9 |
| Wang, Mingyi; Fu, Zongming; Wu, James et al. (2012) MFG-E8 activates proliferation of vascular smooth muscle cells via integrin signaling. Aging Cell 11:500-8 |
| Wang, Mingyi; Zhang, Jing; Telljohann, Richard et al. (2012) Chronic matrix metalloproteinase inhibition retards age-associated arterial proinflammation and increase in blood pressure. Hypertension 60:459-66 |
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