Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells
Language: 
English
Abstract: 

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 microg/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 IkappaB-alpha 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-kappaB. These findings suggest that SAA may contribute to the progress of coronary artery disease.

Author(s): 
Wang, Xinwen
Chai, Hong
Wang, Zehao
Lin, Peter H.
Yao, Qizhi
Chen, Changyi
Item Type: 
Journal Article
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology
Journal Abbreviation: 
Am. J. Physiol. Heart Circ. Physiol.
Publication Date: 
Dec 2008
Publication Year: 
2008
Pages: 
H2399-2408
Volume: 
295
Issue: 
6
ISSN: 
0363-6135
DOI: 
10.1152/ajpheart.00238.2008
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 18931033 PMCID: PMC2614654

Turabian/Chicago Citation

Xinwen Wang, Hong Chai, Zehao Wang, Peter H. Lin, Qizhi Yao and Changyi Chen. Dec 2008. "Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells." American Journal of Physiology. Heart and Circulatory Physiology 295: 6: H2399-2408. 10.1152/ajpheart.00238.2008.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1152/ajpheart.00238.2008 | issn = 0363-6135 | volume = 295 | pages = H2399-2408 | last = Wang | first = Xinwen | coauthors = Chai, Hong, Wang, Zehao, Lin, Peter H., Yao, Qizhi, Chen, Changyi | title = Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells | journal = American Journal of Physiology. Heart and Circulatory Physiology | date = Dec 2008 | pmid = | pmc = }} </ref>