Inhibition of endo-lysosomal function exacerbates vascular calcification

Scientific Reports
Yujun CaiRaul J Guzman

Abstract

Vascular calcification is a pathologic response to mineral imbalances and is prevalent in atherosclerosis, diabetes mellitus, and chronic kidney disease. When located in the media, it is highly associated with increased cardiovascular morbidity and mortality, particularly in patients on dialysis. Vascular calcification is tightly regulated and controlled by a series of endogenous factors. In the present study, we assess the effects of lysosomal and endosomal inhibition on calcification in vascular smooth muscle cells (VSMCs) and aortic rings. We observed that lysosomal function was increased in VSMCs cultured in calcification medium containing 3.5 mM inorganic phosphate (Pi) and 3 mM calcium (Ca2+) for 7 days. We also found that the lysosomal marker lysosome-associated membrane protein 2 was markedly increased and colocalized with osteogenic markers in calcified aortas from vitamin D3-treated rats. Interestingly, both the lysosomal inhibitor chloroquine and the endosomal inhibitor dynasore dose-dependently enhanced Pi + Ca2+-mediated VSMC calcification. Inhibition of lysosomal and endosomal function also promoted osteogenic transformation of VSMCs. Additionally, lysosome inhibition increased Pi-induced medial calcification of a...Continue Reading

References

Jun 22, 2000·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·A P GuérinF Metivier
Oct 9, 2001·Journal of Neuropathology and Experimental Neurology·A U ZaidiK A Roth
Jan 15, 2004·JAMA : the Journal of the American Medical Association·Philip GreenlandRobert C Detrano
May 6, 2005·Cytokine & Growth Factor Reviews·Kohei MiyazonoTakeshi Imamura
Mar 7, 2006·Journal of the American College of Cardiology·Steven P Marso, William R Hiatt
May 13, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Xiao QinRaul J Guzman
Sep 16, 2006·Molecular Aspects of Medicine·Eeva-Liisa Eskelinen
Jul 20, 2007·Nature Reviews. Molecular Cell Biology·J Paul LuzioNicholas A Bright
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
May 17, 2008·Journal of the American College of Cardiology·Raul J GuzmanXiao Qin
Jun 4, 2008·Circulation·Linda L Demer, Yin Tintut
Mar 26, 2009·Annual Review of Biochemistry·Gary J Doherty, Harvey T McMahon
Jul 23, 2009·Biochemical and Biophysical Research Communications·Xiaohui DuanYongfen Qi
Aug 13, 2009·Nature Reviews. Molecular Cell Biology·Paul Saftig, Judith Klumperman
Aug 28, 2010·Journal of the American Society of Nephrology : JASN·Ashwini S Pai, Cecilia M Giachelli
May 27, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sooyeon LeeRalph A Nixon
Jun 7, 2011·Clinical Lipidology·W Gray Jerome
Nov 22, 2011·Antioxidants & Redox Signaling·Patricia Boya
Nov 10, 2012·Journal of the American Society of Nephrology : JASN·Rukshana ShroffCatherine Shanahan
Jan 12, 2013·Diabetes Research and Clinical Practice·Raul J GuzmanC Michael Stein
Mar 5, 2013·International Journal of Cardiology·Chaoyang WenHui Zhong
Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
Jun 4, 2013·Kidney International·Catherine M Shanahan
Apr 18, 2014·European Heart Journal·Peter LanzerCatherine Shanahan
Aug 22, 2014·American Journal of Physiology. Renal Physiology·Neil J Paloian, Cecilia M Giachelli
Dec 2, 2014·Trends in Cardiovascular Medicine·Jane A Leopold
Dec 6, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·W Charles O'NeillRandolph A Hennigar
Oct 1, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ryo SudoHiroshi Wachi
Nov 20, 2015·Atherosclerosis·Takuyu AkiyoshiMasahiro Akishita
Jan 21, 2016·Journal of Geriatric Cardiology : JGC·Wei LiuYu-Jie Zhou

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Citations

Jul 1, 2020·Journal of Cellular and Molecular Medicine·Jiajun ZhouChaoqing Gao
Jun 19, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Owais M BhatPin-Lan Li

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