HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/C2276    most recent 00606.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by House, S. J. Articles by Singer, H. A. Search for Related Content PubMed PubMed Citation Articles by House, S. J. Articles by Singer, H. A.

VASCULAR BIOLOGY

Calcium/calmodulin-dependent protein kinase II- isoform regulation of vascular smooth muscle cell proliferation

¹Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; and ²Upstate/Chemicon Group, Millipore Corporation, Temecula, California

Submitted 6 December 2006 ; accepted in final form 28 January 2007

There is accumulating evidence that Ca²⁺-dependent signaling pathways regulate proliferation and migration of vascular smooth muscle (VSM) cells, contributing to the intimal accumulation of VSM that is a hallmark of many vascular diseases. In this study we investigated the role of the multifunctional serine/threonine kinase, calmodulin (CaM)-dependent protein kinase II (CaMKII), as a mediator of Ca²⁺ signals regulating VSM cell proliferation. Differentiated VSM cells acutely isolated from rat aortic media express primarily CaMKII gene products, whereas passaged primary cultures of de-differentiated VSM cells express primarily CaMKII₂, a splice variant of the gene. Experiments examining the time course of CaMKII isoform modulation revealed the process was rapid in onset following initial dispersion and primary culture of aortic VSM with a significant increase in CaMKII₂ protein and a significant decrease in CaMKII protein within 30 h, coinciding with the onset of DNA synthesis and cell proliferation. Attenuating the initial upregulation of CaMKII₂ in primary cultured cells using small-interfering RNA (siRNA) resulted in decreased serum-stimulated DNA synthesis and cell proliferation in primary culture. In passaged VSM cells, suppression of CaMKII₂ activity by overexpression of a kinase-negative mutant, or suppression of endogenous CaMKII content using multiple siRNAs, significantly attenuated serum-stimulated DNA synthesis and cell proliferation. Cell cycle analysis following either inhibitory approach indicated decreased proportion of cells in G1, an increase in proportion of cells in G2/M, and an increase in polyploidy, corresponding with accumulation of multinucleated cells. These results indicate that CaMKII₂ is specifically induced during modulation of VSM cells to the synthetic phenotypic and is a positive regulator of serum-stimulated proliferation.

calmodulin kinase II; phenotype modulation

This article has been cited by other articles:

				M. Z. Mercure, R. Ginnan, and H. A. Singer CaM kinase II{delta}2-dependent regulation of vascular smooth muscle cell polarization and migration Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1465 - C1475. [Abstract] [Full Text] [PDF]

				Z. Pavicevic, C. C. Leslie, and K. U. Malik cPLA2 phosphorylation at serine-515 and serine-505 is required for arachidonic acid release in vascular smooth muscle cells J. Lipid Res., April 1, 2008; 49(4): 724 - 737. [Abstract] [Full Text] [PDF]

				S. J. House and H. A. Singer CaMKII-{delta} Isoform Regulation of Neointima Formation After Vascular Injury Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 441 - 447. [Abstract] [Full Text] [PDF]