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Ann Thorac Surg 2001;71:1856-1864
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency

^a Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada
^b Department of Internal Medicine, Aoto Hospital, Jikei University School of Medicine, Tokyo, Japan

Accepted for publication January 5, 2001.

Address reprint requests to Dr Del Rizzo, Laboratory for Experimental Cardiovascular Surgery, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Taché Ave, Winnipeg, MB, Canada R2H 2A6
e-mail: delrizzo{at}cc.umanitoba.ca
e-mail: ddelrizzo{at}exchange.hsc.mb.ca

Background. Serotonin can induce proliferation of vascular smooth muscle cells. We assessed the ability of a specific serotonin receptor antagonist, sarpogrelate, to inhibit proliferation of cultured porcine coronary artery smooth muscle cells.

Methods. Cell proliferation and mitotic activity were measured using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide. To determine the effect of sarpogrelate on DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and protein synthesis, radioactive incorporation of ³H-thymidine, ³H-uridine, and ³H-phenylalanine, respectively, was used. Synthesis of DNA was also assessed by flow cytometry with propidium iodide as a fluorochrome.

Results. Serotonin, platelet-derived growth factor, endothelin, and angiotensin II all induced proliferation of porcine coronary artery smooth muscle cells. Sarpogrelate specifically inhibited the serotonin-induced cytokine trigger but did not influence platelet-derived growth factor–, endothelin–, or angiotensin II–induced cell proliferation. Sarpogrelate inhibited the serotonin-induced increase in intracellular free ionized calcium concentration, prevented mitogen-activated protein kinase activation, and down-regulated expression of the protooncogenes c-fos and c-jun. Sarpogrelate acted at the G₁ phase of the cell cycle.

Conclusions. These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts.

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Invited commentary

Norman B. Ratliff
Ann. Thorac. Surg. 2001 71: 1865. [Extract] [Full Text] [PDF]

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