This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sutliff, R. L. Articles by Paul, R. J. Search for Related Content PubMed PubMed Citation Articles by Sutliff, R. L. Articles by Paul, R. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Contractile function Genetically altered mice Endothelium/vascular type/nitric oxide

(Circulation Research. 1999;84:360-364.)
© 1999 American Heart Association, Inc.

Rapid Communication

Phospholamban Is Present in Endothelial Cells and Modulates Endothelium-Dependent Relaxation

Evidence From Phospholamban Gene-Ablated Mice

Roy L. Sutliff, James B. Hoying, Vivek J. Kadambi, Evangelia G. Kranias, Richard J. Paul

From the Departments of Molecular and Cellular Physiology (R.L.S., E.G.K., R.J.P.); Pharmacology and Cell Biophysics (V.J.K., R.J.P.); Molecular Genetics (J.B.H.), University of Cincinnati College of Medicine, Cincinnati, Ohio.

Correspondence to Richard J. Paul, PhD, PO Box 670576, 231 Bethesda Ave, Cincinnati, OH 45267-0576. E-mail Richard.Paul{at}uc.edu

Abstract—Vascular endothelial cells regulate vascular smooth muscle tone through Ca²⁺-dependent production and release of vasoactive molecules. Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca²⁺]_i and contractility in these muscles. In the present study, we report the existence of PLB in the vascular endothelium, a nonmuscle tissue, and provide functional data on PLB regulation of vascular contractility through its actions in the endothelium. Endothelium-dependent relaxation to acetylcholine was attenuated in aorta of PLB-deficient (PLB-KO) mice compared with wild-type (WT) controls. This effect was not due to actions of nitric oxide on the smooth muscle, because sodium nitroprusside–mediated relaxation in either denuded or endothelium-intact aortas was unaffected by PLB ablation. Relative to denuded vessels, relaxation to forskolin was enhanced in WT endothelium-intact aortas. The endothelium-dependent component of this relaxation was attenuated in PLB-KO aortas. To investigate whether these changes were due to PLB, WT mouse aorta endothelial cells were isolated. Both reverse transcriptase–polymerase chain reaction and Western blot analyses revealed the presence of PLB in endothelial cells, which were shown to be >98% pure by diI-acetylated LDL uptake and nuclear counterstaining. These data indicate that PLB is present and modulates vascular function as a result of its actions in endothelial cells. The presence of PLB in endothelial cells opens new fields for investigation of Ca²⁺ regulatory pathways in nonmuscle cells and for modulation of endothelial-vascular interactions.

Key Words: phospholamban • endothelium • vasorelaxation • SERCA • Ca²⁺

This article has been cited by other articles:

				S. A. Kasseckert, C. Schafer, A. Kluger, D. Gligorievski, J. Tillmann, K.-D. Schluter, T. Noll, H. Sauer, H. M. Piper, and Y. Abdallah Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation Cardiovasc Res, July 15, 2009; 83(2): 381 - 387. [Abstract] [Full Text] [PDF]

				H. Taniguchi, I. Mohri, H. Okabe-Arahori, K. Aritake, K. Wada, T. Kanekiyo, S. Narumiya, M. Nakayama, K. Ozono, Y. Urade, et al. Prostaglandin D2 Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury J. Neurosci., April 18, 2007; 27(16): 4303 - 4312. [Abstract] [Full Text] [PDF]

				M. Kim and B. A. Perrino CaM kinase II activation and phospholamban phosphorylation by SNP in murine gastric antrum smooth muscles Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1045 - G1054. [Abstract] [Full Text] [PDF]

				A. N. Carr, B. W. Howard, H. T. Yang, E. Eby-Wilkens, P. Loos, A. Varbanov, A. Qu, J. P. DeMuth, M. G. Davis, A. Proia, et al. Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: Support for an endothelium-dependent mechanism Cardiovasc Res, March 1, 2006; 69(4): 925 - 935. [Abstract] [Full Text] [PDF]

				K. F Frank, B. Bolck, E. Erdmann, and R. H.G Schwinger Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation Cardiovasc Res, January 1, 2003; 57(1): 20 - 27. [Abstract] [Full Text] [PDF]

				K. Nobe, R. L Sutliff, E. G Kranias, and R. J Paul Phospholamban regulation of bladder contractility: evidence from gene-altered mouse models J. Physiol., September 15, 2001; 535(3): 867 - 878. [Abstract] [Full Text] [PDF]

				J. Knapp, P. Bokník, B. Linck, H. Lüss, F. U. Müller, L. Petertönjes, W. Schmitz, and J. Neumann Cantharidin Enhances Norepinephrine-Induced Vasoconstriction in an Endothelium-Dependent Fashion J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 620 - 626. [Abstract] [Full Text]

				S. Rao and A. S. Verkman Analysis of organ physiology in transgenic mice Am J Physiol Cell Physiol, July 1, 2000; 279(1): C1 - C18. [Abstract] [Full Text] [PDF]

				A. G. Brittsan, A. N. Carr, A. G. Schmidt, and E. G. Kranias Maximal Inhibition of SERCA2 Ca2+ Affinity by Phospholamban in Transgenic Hearts Overexpressing a Non-phosphorylatable Form of Phospholamban J. Biol. Chem., April 14, 2000; 275(16): 12129 - 12135. [Abstract] [Full Text] [PDF]

				F. M. Faraci and C. D. Sigmund Vascular Biology in Genetically Altered Mice : Smaller Vessels, Bigger Insight Circ. Res., December 3, 1999; 85(12): 1214 - 1225. [Full Text] [PDF]