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). 10 Royal Brompton & Harefield Hospitals, Imperial College London, London, UK.Īrterial stiffness is a hallmark of vascular ageing that precedes and strongly predicts the development of cardiovascular diseases.9 Department of Internal Medicine, Cantonal Hospital Baden, Baden, Switzerland.8 Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.7 Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.6 Department of Research and Education, University Hospital Zurich, Zurich, Switzerland. ![]() 5 Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland. ![]()
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