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المؤلفPintus, Gianfranco
المؤلفGiordo, Roberta
المؤلفYushi, Wang
المؤلفWanqu, Zhu
المؤلفSoo, Hyuk Kim
المؤلفLi, Zhang
المؤلفLeng, Ni
المؤلفJing, Zhang
المؤلفRichard, Telljohann
المؤلفKimberly, R. McGraw
المؤلفRobert, E. Monticone
المؤلفChloe, Ferris
المؤلفLijuan, Liu
المؤلفMingyi, Wang
المؤلفEdward, G. Lakatta
تاريخ الإتاحة2018-06-24T10:37:04Z
تاريخ النشر2018-06-05
اسم المنشورOncotarget
المعرّفhttp://dx.doi.org/10.18632/oncotarget.25499
الاقتباسPintus, G., Giordo, R., Wang, Y., Zhu, W., Kim, S. H., Zhang, L., … Lakatta, E. G. (2018). Reduced vasorin enhances angiotensin II signaling within the aging arterial wall. Oncotarget, 9(43), 27117–27132. http://doi.org/10.18632/oncotarget.25499
معرّف المصادر الموحدhttp://hdl.handle.net/10576/6746
الملخصThe glycosylated protein vasorin physically interacts with the transforming growth factor-beta1 (TGF-β1) and functionally attenuates its fibrogenic signaling in the vascular smooth muscle cells (VSMCs) of the arterial wall. Angiotensin II (Ang II) amplifies TGF-β1 activation in the VSMCs of the arterial wall with aging. In this study, we hypothesized that a reduced expression of the protein vasorin plays a contributory role in magnifying Ang II-associated fibrogenic signaling in the VSMCs of the arterial wall with aging. The current study shows that vasorin mRNA and protein expression were significantly decreased both in aortic wall and VSMCs from old (30 mo) vs. young (8 mo) FXBN rats. Exposing young VSMCs to Ang II reduced vasorin protein expression to the levels of old untreated cells while treating old VSMCs with the Ang II type AT1 receptor antagonist Losartan upregulated vasorin protein expression up to the levels of young. The physical interaction between vasorin and TGF-β1 was significantly decreased in old vs. young VSMCs. Further, exposing young VSMCs to Ang II increased the levels of matrix metalloproteinase type II (MMP-2) activation and TGF-β1 downstream molecules p-SMAD-2/3 and collagen type I production up to the levels of old untreated VSMCs, and these effects were substantially inhibited by overexpressing vasorin. Administration of Ang II to young rats (8 mo) for 28 days via an osmotic minipump markedly reduced the expression of vasorin. Importantly, vasorin protein was effectively cleaved by activated MMP-2 both in vitro and in vivo. Administration of the MMP inhibitor, PD 166793, for 6 mo to young adult (18 mo) via a daily gavage markedly increased levels of vasorin in the aortic wall. Thus, reduced vasorin amplifies Ang II profibrotic signaling via an activation of MMP-2 in VSMCs within the aging arterial wall.
اللغةen
الناشرImpact Journals
الموضوعaging
arterial remodeling
VSMC
vasorin
collagen
العنوانReduced vasorin enhances angiotensin II signaling within the aging arterial wall
النوعArticle
الصفحات27117-27132
رقم العدد43
رقم المجلد9
ESSN1949-2553
dc.accessType Open Access


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