Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice

Stem Cells International
Xueling YueXianwu Cheng

Abstract

Aging is a major risk factor for cardiovascular disease. Cysteine protease cathepsin K (CatK) has been implicated in the process of angiogenesis, but the exact roles of individual CatK in vessel formation during aging are poorly understood. To study the putative role of CatK in ischemia-induced angiogenesis, we applied a hindlimb ischemia model to aged wild-type (CatK+/+) and CatK-deficient (CatK-/-) mice. A serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in the aged CatK-/-mice was impaired throughout the follow-up period. On postoperative day 14, CatK deficiency had also impaired capillary formation. CatK deficiency reduced the levels of cleaved Notch1, phospho-Akt, and/or vascular endothelial growth factor (VEGF) proteins in the ischemic muscles and bone marrow-derived c-Kit+ cells. A flow cytometry analysis revealed that CatK deficiency reduced the numbers of endothelial progenitor cell (EPC)-like CD31+/c-Kit+ cells in the peripheral blood as well as the ischemic vasculature. In vitro experiments, CatK-/- impaired bone-derived c-Kit+ cellular functions (migration, invasion, proliferation, and tubulogenesis) in aged mice. Our findings demonstrated that aging impaire...Continue Reading

References

Sep 21, 2002·Lancet·Eriko Tateishi-YuyamaUNKNOWN Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators
Jan 28, 2003·Journal of Cellular Physiology·Tatsuya IsoYasuo Hamamori
Jan 25, 2005·Nature Medicine·Carmen UrbichStefanie Dimmeler
Apr 6, 2005·Circulation·Florian P LimbourgJames K Liao
Feb 14, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Victor W M van HinsberghPaul H A Quax
Dec 13, 2006·Circulation Research·Kyosuke TakeshitaJames K Liao
Jul 16, 2008·Journal of Molecular and Cellular Cardiology·Carmen UrbichStefanie Dimmeler
Mar 23, 2010·The American Journal of Pathology·Noriaki ShimadaIkuo Morita
Apr 22, 2011·Nature Reviews. Cancer·Prathibha RanganathanAnthony J Capobianco
Dec 18, 2013·Hypertension·Lina HuMasafumi Kuzuya
Mar 5, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·David A Drachman
Jun 5, 2014·Nature Communications·Haiying JiangMasafumi Kuzuya
Feb 11, 2015·International Journal of Cardiology·Xiang LiMasafumi Kuzuya
Feb 19, 2015·Aging Cell·Yinan HuaSreejayan Nair
Jul 2, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Hongxian WuToyoaki Murohara
Jun 6, 2017·Aging and Disease·Guangxian ZhaoMasafumi Kuzuya
Oct 6, 2017·Journal of Atherosclerosis and Thrombosis·Hongxian WuXianwu Cheng
Mar 9, 2018·Circulation Research·Ayman Samman TahhanArshed A Quyyumi
Apr 22, 2018·Nature Reviews. Cardiology·Cong-Lin LiuGuo-Ping Shi
Jun 1, 2018·Current Drug Targets·Haiying JiangXian Wu Cheng
Nov 23, 2018·Journal of Molecular and Cellular Cardiology·Wenqian FangGuo-Ping Shi
Jul 13, 2019·Journal of the American Heart Association·Hailong WangXian Wu Cheng
Oct 28, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Wenhu XuXian Wu Cheng

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Methods Mentioned

BETA
electrophoresis
confocal microscopy
flow cytometry
amputation

Software Mentioned

Exe
SPSS

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