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) Supplemental Figures and Tables All Versions of this Article: 295/6/H2399    most recent 00238.2008v1 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 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 Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Chen, C. Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Chen, C.

Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

Molecular Surgeon Research Center and Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas

Submitted 6 March 2008 ; accepted in final form 15 October 2008

The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 µg/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IB- after SAA treatment. Consequently, the antioxidants seleno-L-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-B. These findings suggest that SAA may contribute to the progress of coronary artery disease.

endothelial nitric oxide synthase; reactive oxygen species; antioxidant; mitogen-activated protein kinase; nuclear factor-B

This article has been cited by other articles:

				N. T. Jenkins, S. Witkowski, E. E. Spangenburg, and J. M. Hagberg Effects of acute and chronic endurance exercise on intracellular nitric oxide in putative endothelial progenitor cells: role of NAPDH oxidase Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1798 - H1805. [Abstract] [Full Text] [PDF]