siMMP-2-treated mice showed increased elastin-to-collagen ratio, lower plasma desmosine (DES), enhanced phosphorylation of endothelial nitric oxide synthase (eNOS), and higher levels of vascular cyclic guanosine monophosphate (cGMP). MMP-2 knockdown reduced vascular MMP-2 levels and attenuated age-dependent carotid stiffness. Carotid PWV was assessed at baseline, 2 and 4 weeks after start of the treatment. Old WT mice (18- to 21-month old) were treated for 4 weeks with either MMP-2 or scrambled (Scr) siRNA via tail vein injection. Carotid PWV as well as vascular and circulating MMP-2 were elevated with increasing age in mice.
MMP-2 levels in the carotid artery and plasma of young (3 months) and old (20-25 months) WT mice were determined. Pulse wave velocity (PWV) was assessed in right carotid artery of wild-type (WT) mice from different age groups. Thus, we aimed to investigate the efficacy of MMP-2 knockdown using small-interfering RNA (siRNA) on age-dependent arterial stiffness. However, the mechanistic link between age-dependent arterial stiffness and MMP-2 remains unclear. Age-dependent stiffening of large elastic arteries is primarily attributed to increased levels of matrix metalloproteinase-2 (MMP-2).
6 Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.5 Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.4 Department of Medicine, Jagiellonian University Collegium Medicum, Cracow, Poland.3 Institute of Cardiovascular and Medical Science, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.2 Department of Internal Medicine, University of Genoa, Genoa, Italy.
1 Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, CH-8952 Schlieren, Switzerland.
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