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) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Li, S.-l. Articles by Natarajan, R. Search for Related Content PubMed PubMed Citation Articles by Li, S.-l. Articles by Natarajan, R. Social Bookmarking                What's this?

Enhanced Proatherogenic Responses in Macrophages and Vascular Smooth Muscle Cells Derived From Diabetic db/db Mice

From the Department of Diabetes, Beckman Research Institute of the City of Hope, Duarte, California

Address correspondence and reprint requests to Rama Natarajan, PhD, Gonda Diabetes Research Center, Beckman Research Institute of the City of Hope, 1500 East Duarte Rd., Duarte, CA 91010. E-mail: rnatarajan{at}coh.org

Abbreviations: AGE, advanced glycation end product; COX-2, cyclooxygenase-2; CREB, cAMP response element–binding protein; DME, Dulbecco’s modified Eagle’s; ELISA, enzyme-linked immunosorbent assay; ERK, extracellular signal–regulated kinase; IFN, interferon; IKK, inhibitor of nuclear factor-B kinase; IL, interleukin; JAK, Janus-family tyrosine kinase; MCP-1, monocyte chemoattractant protein-1; MAPK, mitogen-activated protein kinase; MVSMC, aortic vascular smooth muscle cell from mice; NF-B, nuclear factor-B; PDGF, platelet-derived growth factor; STAT, signal transducer and activator of transcription; Th, T-helper-type; TNF-, tumor necrosis factor-; VSMC, vascular smooth muscle cell

Diabetes is associated with enhanced inflammatory responses and cardiovascular complications such as atherosclerosis. However, it is unclear whether similar responses are present in cells derived from experimental animal models of diabetes. We examined our hypothesis that macrophages and short-term cultured vascular smooth muscle cells (VSMCs) derived from obese, insulin-resistant, and diabetic db/db mice would exhibit increased proatherogenic responses relative to those from control db/+ mice. We observed that macrophages from db/db mice exhibit significantly increased expression of key inflammatory cytokines and chemokines as well as arachidonic acid–metabolizing enzymes cyclooxygenase-2 and 12/15-lipoxygenase that generate inflammatory lipids. Furthermore, VSMCs derived from db/db mice also showed similar enhanced expression of inflammatory genes. Expression of inflammatory genes was also significantly increased in aortas derived from db/db mice. Both macrophages and VSMCs from db/db mice demonstrated significantly increased oxidant stress, activation of key signaling kinases, and transcription factors cAMP response element–binding protein and nuclear factor-B, involved in the regulation of atherogenic and inflammatory genes. Interestingly, VSMCs from db/db mice displayed enhanced migration as well as adhesion to WEHI mouse monocytes relative to db/+. Thus, the diabetic milieu and a potential hyperglycemic memory can induce aberrant behavior of vascular cells. These new results demonstrate that monocyte/macrophages and VSMCs derived from db/db mice display a "preactivated" and proinflammatory phenotype associated with the pathogenesis of diabetic vascular dysfunction and atherosclerosis.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Devaraj, A. T. Cheung, I. Jialal, S. C. Griffen, D. Nguyen, N. Glaser, and T. Aoki Evidence of Increased Inflammation and Microcirculatory Abnormalities in Patients With Type 1 Diabetes and Their Role in Microvascular Complications Diabetes, November 1, 2007; 56(11): 2790 - 2796. [Abstract] [Full Text] [PDF]

				J. F. Navarro, C. Mora, M. Gomez, M. Muros, C. Lopez-Aguilar, and J. Garcia Influence of Renal Involvement on Peripheral Blood Mononuclear Cell Expression Behavior of Tumor Necrosis Factor-{alpha} And Interleukin-6 in Type 2 Diabetic Patients Nephrol. Dial. Transplant., October 2, 2007; (2007) gfm674v1. [Abstract] [Full Text] [PDF]

				M. Rajesh, P. Mukhopadhyay, S. Batkai, G. Hasko, L. Liaudet, V. R. Drel, I. G. Obrosova, and P. Pacher Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H610 - H619. [Abstract] [Full Text] [PDF]

				C.-P. Liang, S. Han, T. Senokuchi, and A. R. Tall The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis Circ. Res., June 8, 2007; 100(11): 1546 - 1555. [Abstract] [Full Text] [PDF]