Inhibition of protein kinase Calpha prevents endothelial cell migration and vascular tube formation in vitro and myocardial neovascularization in vivo

Circulation Research
Aihong WangJ A Ware

Abstract

Although protein kinase C (PKC) activation is required for endothelial cell (EC) growth, migration, adhesion, and vessel formation, the role of individual PKC isoenzymes in these events is not defined. Because PKCalpha has been previously linked with enhanced EC migration and response to angiogenic growth factors, we characterized a specific phosphorothioate-modified 21-mer antisense PKCalpha (AS-PKCalpha). AS-PKCalpha (500 nmol/L) prevented the expression of PKCalpha protein by 90% in human ECs and did not reduce the expression of any other PKC isoenzyme. AS-PKCalpha reduced human EC migration by 64% compared with its control oligonucleotide in a "scratch" wounding assay, and AS-PKCalpha reduced human EC adhesion to the extracellular matrix protein vitronectin by 18%. Phosphorylation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) induced by vascular endothelial growth factor was inhibited by 30% in human ECs transfected with AS-PKCalpha. Compared with control, AS-PKCalpha also reduced the number of EC tubes formed in a 3D type I collagen gel assay by 37.5%. Finally, using an osmotic minipump, we infused AS-PKCalpha into mice in which myocardial infarction was induced by coronary ligation and fo...Continue Reading

References

Sep 11, 1979·Nucleic Acids Research·H Donis-Keller
Dec 1, 1995·Science·M FriedlanderD A Cheresh
Apr 1, 1994·The Journal of Clinical Investigation·R MorishitaV J Dzau
Jun 1, 1996·The Journal of Surgical Research·S YamamuraK C Kent
Aug 9, 1996·Science·M LeitgesA Tarakhovsky
Feb 1, 1997·Nature Medicine·J A Ware, M Simons
Jul 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J Hofmann
Jul 1, 1997·The American Journal of Physiology·G C HaralabopoulosM E Maragoudakis
Feb 12, 1998·The Journal of Biological Chemistry·O TraubB C Berk
Sep 11, 1998·Science·M R Sierra-HonigmannJ R Flores-Riveros
Apr 29, 2000·Trends in Pharmacological Sciences·K J WayG L King

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Citations

Mar 22, 2005·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Fredrik Ghosh, Karin Gjörloff
Mar 12, 2004·The Journal of Surgical Research·Ponnandai SomasundarLinda Vona-Davis
Aug 19, 2003·Trends in Cardiovascular Medicine·Chieko Mineo, Philip W Shaul
Nov 1, 2007·Nature Reviews. Molecular Cell Biology·Mark R MorganMark D Bass
Jan 12, 2010·Journal of Burn Care & Research : Official Publication of the American Burn Association·Areck A UcuzianHoward P Greisler
Mar 4, 2005·BMC Cell Biology·Jianfeng QinJustin D Pearlman
Dec 12, 2012·Indian Journal of Endocrinology and Metabolism·Sunil K KotaKirtikumar D Modi
May 16, 2002·The Journal of Cell Biology·Arie HorowitzMichael Simons
Jun 5, 2012·Journal of Diabetes and Its Complications·Umesh C S YadavKota V Ramana
Aug 17, 2010·Biochemical and Biophysical Research Communications·Zhong-Xiu-Zi GaoJin-Hua Zheng
Dec 24, 2005·The Journal of Investigative Dermatology·Sirosh M BokhariVaishali Chaudhuri
Jun 14, 2005·Experimental Cell Research·Frank EntschladenKurt S Zaenker
Jun 7, 2005·Expert Opinion on Therapeutic Targets·Patrick M Martin, Isa M Hussaini
Dec 9, 2009·Trends in Pharmacological Sciences·Olga Konopatskaya, Alastair W Poole
Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mi ZhouJin Xu
May 4, 2004·Biochemical and Biophysical Research Communications·Michael K JonesDolgor Baatar
Jun 19, 2007·The Journal of Surgical Research·Kentaro KamiyaBo Liu
Dec 25, 2002·Medicinal Research Reviews·Alexandra MartinDavid C Sane
Aug 26, 2003·Journal of Cellular Biochemistry·Jianqiang Wu, Nader Sheibani
Sep 6, 2005·Circulation Research·Pinaki ChaudhuriLinda M Graham
Mar 5, 2008·Journal of Surgical Oncology·Kai-Yuan LinSheng-Hsuan Chen
Feb 21, 2009·Journal of Cellular Physiology·Peng ZhangHandong Yang
Nov 6, 2018·Journal of Cellular Physiology·Toshihiro SeraSusumu Kudo
May 25, 2007·The Journal of Biological Chemistry·Wei ZhangVedat Schwenger
Sep 12, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jirka GrosseDaniela Grimm
Oct 6, 2006·Current Opinion in Anaesthesiology·Dawn M Pedrotty, Laura E Niklason
Dec 6, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrea S RothmeierStefan Zahler
Jan 4, 2003·The Journal of Biological Chemistry·Chieko MineoPhilip W Shaul
Sep 19, 2003·American Journal of Physiology. Cell Physiology·John H TinsleySarah Y Yuan
Aug 20, 2005·Cellular Signalling·Christer Larsson
Jul 19, 2006·Prostaglandins & Other Lipid Mediators·Brian ThompsonRamadan I Sha'afi

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