Sarpogrelate Inhibits Intimal Hyperplasia and Proliferation of Smooth Muscle Cells in Balloon-Injured Carotid Artery of Rat_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENYue-xin , WANGWen-da , YEWei , LITian-jia ,  LIUChang-wei

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China;

Corresponding author：

LIUChang-wei, Email: liucw@vip.sina.com

Keywords：

Sarpogrelate; Clopidogrel; Intimal hyperplasia; Carotid artery; Proliferative cell nuclear antigen

DOI：

10.7507/1007-9424.20150151

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Objective To assess the inhibitory ability of sarpogrelate on neointimal hyperplasia of carotid artery in rat balloon-injuried model, and to compare the proliferation of vascular smooth muscle cell (VSMC) by monitoring the expression of proliferative cell nuclear antigen (PCNA). Methods Twenty-four male SD rats (SPF, 8 weeks) were allocated prospectively and randomly into 3 groups: blank group, sarpogrelate group, and clopidogrel group. Each group included 8 rats. All the rats were fed high-fat diet for 1 week before the operation. No drug was fed in the blank group, and sarpogrelate 100 mg/(kg·d) or clopidogrel 20 mg/(kg·d) was fed in the sarpogrelate group or clopidogrel group respectively. The carotid artery of rat was dilated by the Forgarty balloon catheter. The rats were killed 2 weeks later and the samples were got in the balloon-injuried carotid arteries. Histomorphological analysis and immunohistochemical analysis were proceeded. The thickness ratio and area ratio of intima and media, the ratio of PCNA positive cells and PCNA absorbance were calculated among the three groups. Results Compared with the blank group, the average intimal thickness, average intimal area, thickness ratio of intima and media, area ratio of intima and media, PCNA absorbance, and ratio of PCNA positive cells were significant decreased in the sarpogrelate group (P < 0.001) and the clopidogrel group (P < 0.001), but which had no significant differences between the sarpogrelate group and the clopidogrel group (P > 0.05). There was no significant difference in the average media thickness or area among the 3 groups (P > 0.05). Conclusion Sarpogrelate and clopidogrel could significantly reduce the thickness or area of intima, the absorbance of PCNA and the ratio of PCNA positive cells.

Citation： CHENYue-xin, WANGWen-da, YEWei, LITian-jia, LIUChang-wei. Sarpogrelate Inhibits Intimal Hyperplasia and Proliferation of Smooth Muscle Cells in Balloon-Injured Carotid Artery of Rat. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(5): 571-575. doi: 10.7507/1007-9424.20150151 Copy

1.	Golledge J, Ferguson K, Ellis M, et al. Outcome of femoropopliteal angioplasty. Ann Surg, 1999, 229(1):146-153.
2.	Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med, 2006, 354(18):1879-1888.
3.	Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery:twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv, 2010, 3(3):267-276.
4.	Sharma SK, Del Rizzo DF, Zahradka P, et al. Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells:implications for long-term graft patency. Ann Thorac Surg, 2001, 71(6):1856-1865.
5.	曾宏, 孙晓磊, 何虎强, 等.盐酸沙格雷酯治疗慢性下肢动脉硬化闭塞症的近期临床疗效观察.中国普外基础与临床杂志, 2013, 20(6):661-663.
6.	方青波, 阿力木江.盐酸沙格雷酯治疗血栓闭塞性脉管炎的近期疗效.中国普外基础与临床杂志, 2014, 21(6):749-750.
7.	Sharma SK, Zahradka P, Chapman D, et al. Inhibition of serotonininduced vascular smooth muscle cell proliferation by sarpogrelate. J Pharmacol Exp Ther, 1999, 290(3):1475-1481.
8.	Fujita M, Mizuno K, Ho M, et al. Sarpogrelate treatment reduces restenosis after coronary stenting. Am Heart J, 2003, 145(3):E16.
9.	Waksman R, Pakala R, Roy P, et al. Effect of clopidogrel on neointimal formation and inflammation in balloon-denuded and radiated hypercholesterolemic rabbit iliac arteries. J Interv Cardiol, 2008, 21(2):122-128.
10.	Douglas JS Jr. Pharmacologic approaches to restenosis prevention. Am J Cardiol, 2007, 100(5A):10K-16K.
11.	Goncu T, Yavuz S, Çekirdekçi A, et al. The effect of perindopril on the intimal hyperplasia occurring after vascular injury. Turkish J Thorac and Cardiovasc Surg, 2001, 9:109-114.
12.	Uchida K, Sasahara M, Morigami N, et al. Expression of plateletderived growth factor B-chain in neointimal smooth muscle cells of balloon injured rabbit femoral arteries. Atherosclerosis, 1996, 124(1):9-23.
13.	Olson NE, Chao S, Lindner V, et al. Intimal smooth muscle cell proliferation after balloon catheter injury. The role of basic fibroblast growth factor. Am J Pathol, 1992, 140:1017-1023.
14.	Göncü T, Tiryakioğlu O, Ozcan A, et al. Inhibitory effects of ticlopidine and clopidogrel on the intimal hyperplastic response after arterial injury. Anadolu Kardiyol Derg, 2010, 10(1):11-16.
15.	Koyama N, Hart CE, Clowes AW. Different functions of the platelet-derived growth factor-alpha and-beta receptors for the migration and proliferation of cultured baboon smooth muscle cells. Circ Res, 1994, 75(4):682-691.
16.	Li J, Zhang H, Zhang C. Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion:mechanisms and therapeutic implications. J Mol Cell Cardiol, 2012, 52(4):865-872.
17.	Cortelekoglu T, Bozkurt AK, Ustundag N, et al. The effects of clopidogrel and Calcium dobesilate on intimal hyperplasia following vascular injury. Acta Chir Belg, 2006, 106(2):206-210.
18.	Nishihira K, Yamashita A, Tanaka N, et al. Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery. J Thromb Haemost, 2006, 4(1):247-255.
19.	Machida T, Iizuka K, Hirafuji M. 5-hydroxytryptamine and its receptors in systemic vascular walls. Biol Pharm Bull, 2013, 36(9):1416-1419.
20.	Nagatomo T, Rashid M, Abul Muntasir H, et al. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol Ther, 2004, 104(1):59-81.
21.	Fujita M, Minamino T, Sanada S, et al. Selective blockade of serotonin 5-HT2A receptor increases coronary blood flow via augmented cardiac nitric oxide release through 5-HT1B receptor in hypoperfused canine hearts. J Mol Cell Cardiol, 2004, 37(6):1219-1223.
22.	Yasui H, Hakozaki T, Date A, et al. Real-time chemiluminescent imaging and detection of reactive oxygen species generated in the UVB-exposed human skin equivalent model. Biochem Biophys Res Commun, 2006, 347(1):83-88.
23.	Watanabe T, Sato K, Itoh F, et al. The roles of salusins in atherosclerosis and related cardiovascular diseases. J Am Society Hyperten, 2011, 5(5):359-365.
24.	Liu LL, Wu YQ, Song Z, et al. Effect of salusin-βon the proliferation of vascular smooth muscle cells and the underlying mechanisms. Chem Pharm Bull, 2010, 26(5):666-669.
25.	Sobel M, Verhaeghe R; American College of Chest Physicians. Antithrombotic therapy for peripheral artery occlusive disease:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 2008, 133(6 Suppl):815S-843S.

1. Golledge J, Ferguson K, Ellis M, et al. Outcome of femoropopliteal angioplasty. Ann Surg, 1999, 229(1):146-153.
2. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med, 2006, 354(18):1879-1888.
3. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery:twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv, 2010, 3(3):267-276.
4. Sharma SK, Del Rizzo DF, Zahradka P, et al. Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells:implications for long-term graft patency. Ann Thorac Surg, 2001, 71(6):1856-1865.
5. 曾宏, 孙晓磊, 何虎强, 等.盐酸沙格雷酯治疗慢性下肢动脉硬化闭塞症的近期临床疗效观察.中国普外基础与临床杂志, 2013, 20(6):661-663.
6. 方青波, 阿力木江.盐酸沙格雷酯治疗血栓闭塞性脉管炎的近期疗效.中国普外基础与临床杂志, 2014, 21(6):749-750.
7. Sharma SK, Zahradka P, Chapman D, et al. Inhibition of serotonininduced vascular smooth muscle cell proliferation by sarpogrelate. J Pharmacol Exp Ther, 1999, 290(3):1475-1481.
8. Fujita M, Mizuno K, Ho M, et al. Sarpogrelate treatment reduces restenosis after coronary stenting. Am Heart J, 2003, 145(3):E16.
9. Waksman R, Pakala R, Roy P, et al. Effect of clopidogrel on neointimal formation and inflammation in balloon-denuded and radiated hypercholesterolemic rabbit iliac arteries. J Interv Cardiol, 2008, 21(2):122-128.
10. Douglas JS Jr. Pharmacologic approaches to restenosis prevention. Am J Cardiol, 2007, 100(5A):10K-16K.
11. Goncu T, Yavuz S, Çekirdekçi A, et al. The effect of perindopril on the intimal hyperplasia occurring after vascular injury. Turkish J Thorac and Cardiovasc Surg, 2001, 9:109-114.
12. Uchida K, Sasahara M, Morigami N, et al. Expression of plateletderived growth factor B-chain in neointimal smooth muscle cells of balloon injured rabbit femoral arteries. Atherosclerosis, 1996, 124(1):9-23.
13. Olson NE, Chao S, Lindner V, et al. Intimal smooth muscle cell proliferation after balloon catheter injury. The role of basic fibroblast growth factor. Am J Pathol, 1992, 140:1017-1023.
14. Göncü T, Tiryakioğlu O, Ozcan A, et al. Inhibitory effects of ticlopidine and clopidogrel on the intimal hyperplastic response after arterial injury. Anadolu Kardiyol Derg, 2010, 10(1):11-16.
15. Koyama N, Hart CE, Clowes AW. Different functions of the platelet-derived growth factor-alpha and-beta receptors for the migration and proliferation of cultured baboon smooth muscle cells. Circ Res, 1994, 75(4):682-691.
16. Li J, Zhang H, Zhang C. Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion:mechanisms and therapeutic implications. J Mol Cell Cardiol, 2012, 52(4):865-872.
17. Cortelekoglu T, Bozkurt AK, Ustundag N, et al. The effects of clopidogrel and Calcium dobesilate on intimal hyperplasia following vascular injury. Acta Chir Belg, 2006, 106(2):206-210.
18. Nishihira K, Yamashita A, Tanaka N, et al. Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery. J Thromb Haemost, 2006, 4(1):247-255.
19. Machida T, Iizuka K, Hirafuji M. 5-hydroxytryptamine and its receptors in systemic vascular walls. Biol Pharm Bull, 2013, 36(9):1416-1419.
20. Nagatomo T, Rashid M, Abul Muntasir H, et al. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol Ther, 2004, 104(1):59-81.
21. Fujita M, Minamino T, Sanada S, et al. Selective blockade of serotonin 5-HT2A receptor increases coronary blood flow via augmented cardiac nitric oxide release through 5-HT1B receptor in hypoperfused canine hearts. J Mol Cell Cardiol, 2004, 37(6):1219-1223.
22. Yasui H, Hakozaki T, Date A, et al. Real-time chemiluminescent imaging and detection of reactive oxygen species generated in the UVB-exposed human skin equivalent model. Biochem Biophys Res Commun, 2006, 347(1):83-88.
23. Watanabe T, Sato K, Itoh F, et al. The roles of salusins in atherosclerosis and related cardiovascular diseases. J Am Society Hyperten, 2011, 5(5):359-365.
24. Liu LL, Wu YQ, Song Z, et al. Effect of salusin-βon the proliferation of vascular smooth muscle cells and the underlying mechanisms. Chem Pharm Bull, 2010, 26(5):666-669.
25. Sobel M, Verhaeghe R; American College of Chest Physicians. Antithrombotic therapy for peripheral artery occlusive disease:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 2008, 133(6 Suppl):815S-843S.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Sarpogrelate Inhibits Intimal Hyperplasia and Proliferation of Smooth Muscle Cells in Balloon-Injured Carotid Artery of Rat

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