Full Text:


Ǵм Vol.24_No.2 Suppl. P.S373-383, Dec. 2007

Original Article

Ȱ ɸī

Differential Expression of Chemokines in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rat and Normotensive Rat

, ڼҿ*,
б ǰ ̻б, б*
åڣ, 뱸 5 317-1, б ǰ ̻б
Tel: (053) 620-4363, Fax: (053) 653-6628
E-mail: heesun@med.yu.ac.kr

December 30, 2007


BackgroundThe action of chemokines to the vascular inflammation plays a pathogenic role in the development and maintenance of hypertension.
Materials and methodsIn the present study, the expression of chemokine IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of normotensive Wister-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). We used real-time PCR and western blotting.
ResultThe expressions of IL-8/CXCL8, and MCP-1/CCL2 mRNA were stronger in VSMC from SHR than in WKY. However, the expression of RANTES/CCL5 was stronger in VSMC from WKY than in SHR. Expressions of CXCR1, CCR2, CD14 and PPAR mRNA were stronger in VSMC from WKY than in SHR. Expressions of LPS-induced IL-8/CXCL8 and MCP-1/CCL2 mRNA were stronger in VSMC from SHR, but expression of LPS-induced RANTES/CCL5 was stronger in VSMC from WKY. A PPAR- ligand, 15-deoxy-?12,14- prostaglandin J2 (15d-PGJ2) which possesses anti-inflammatory activity suppressed the expressions of LPS-induced IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 in VSMC from WKY and the expressions of LPS-induced MCP-1/CCL2 and RANTES/CCL5 expressions in SHR. But, the expression of LPS-induced IL-8/CXCL8 mRNA in SHR was increased by 15d- PGJ2. Angiotensin II (AngII) also induced IL-8/CXCL8 and MCP-1/CCL2 mRNA expressions in VSMC from SHR, but inhibited the expression of RANTES/CCL5 mRNA. Activities of LPS, or AngII-induced MAP kinases were stronger in VSMC from SHR than in WKY. Expression of AngII-induced IL-8/CXCL8 mRNA was associated with ERK phathway, and the expression of AngII-induced MCP-1/CCL2 mRNA was associated with p38 pathway, and the inhibition of RANTES/CCL5 mRNA by AngII was not associated with MAP Kinases pathways.
ConclusionChemokine IL-8/CXCL8 and MCP-1/CCL2, not RANTES/CCL5, has a possibility to play a critical role in the pathogenesis of hypertension in the SHR.

Key Words: Chemokine, MAP kinase, Gene expression


1. Alexander RW. Hypertension and the patho- genesis of atherosclerosis. Hypertension 1995; 25:155-61.

2. Gerszten RE. Pleiotropic effects of chemokines in vascular lesion development. Artherioscler Thromb Vasc Biol 2002;22:528-9.

3. Luster AD. Chemokines?chemotactic cytokines that mediate inflammation. The New England J Med 1998;338:436-45.

4. Spinetti G, Wang M, Monticone R, Zhang J, Zhao D, Lakatta EG. Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler Thromb Vasc Biol 2004;24:1397-402.

5. Ishibashi M, Hiasa KI, Zhao Q, et al. Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocyte in hypertension- induced vascular inflammation and remodeling. Circ Res 2004;94:1203-10.

6. Capers QI, Alexander RW, Lou P, et al. Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 1997;30:1397-402.

7. Parissis JT, Korovesis S, Giazitzoglou E, Kalivas P, Katritsis D. Plasma profile of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1. Int J Cardiol 2002; 83:13-21.

8. Zhang Y, Griendling KK, Dikalova A, Owens GK, Talyor WR. Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2. Hypertension 2005;46:732-7.

9. Rodriguez-Iturbe B, Vaziri ND, Herrera-Acosta J, Johnson RJ. Oxidative stress, renal infiltration of immune cells and salt-sensitive hypertension: all for one and one for all. Am J Physiol 2004;286:F606-F16.

10. Chen XL, Tummala PE, Olbrych MT, Alexander RW, Medford RM. Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Circ Res 1998;83:952-9.

11. Xie QY, Sun M, Yang TL, Sun ZL. Losartan reduces monocyte chemoattractant protein-1 expression in aortic tissues of 2K1C hyperten- sive rats. Int J Cardiol 2006;110:60-6.

12. Boekholdt S, Peters R, Hack CE, et al. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women. Arterioscler Thromb Vasc Biol 2004;24:1503-08.

13. Barbier O, Torra IP, Duguay Y, Fruchart JC, Glineur C, Staels B. Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2002;22:717-26.

14. Calnek DS, Mazzella L, Roser S, Roman J, Hart CM. Peroxisome proliferators-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 2003;23:52-7.

15. Dobrian AD, Schriver SD, Khraibi AA, Prewitt RL. Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity. Hypertension 2004;43:48-56.

16. Jiang C, Ting AT, Seed B. PPAR-agonists inhibit production of monocyte inflammatory cytokines. Nature 1998;391:82-6.

17. Rajagopalan S, Kurz S, Munzel T, et al. Angiotensin II mediated hypertension in the rat increase vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916-23.

18. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994;74:1141-8.

19. Touyz RM, He G, El Mabrouk M, Diep Q, Mardigyan V, Schiffrin EL. Differential activation of extracellular signal-regulated protein kinase 1/2 and p38 mitogen activated-protein kinase by AT1 receptors in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats. Hypertension 2001;19:553-9.