Molecular Human Reproduction, Vol. 5, No. 2, 139-145,
February 1999
© 1999 European Society of Human Reproduction and Embryology
Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of 
-smooth muscle actin, calponin h1 and p27
1 Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3–1–1 Asahi, Matsumoto 390–8621, and 2 Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606–8397, Japan
Mast cells are widely distributed in human tissues, including the human uterus. However, the function of mast cells in uterine smooth muscle has not been clearly established. Mast cells possess secretory granules containing such substances as heparin, serotonin, histamine and many cytokines. To help establish the role of mast cells in the human myometrium, the action of heparin was investigated using smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under heparin treatment. Western blotting analysis showed that markers of SMC differentiation such as 
-smooth muscle actin (-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by heparin, whereas cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these results indicate that heparin inhibits the proliferation of myometrial and leiomyomal SMC through the induction of -SMA, calponin h1 and p27. We suggest that heparin from mast cells may induce differentiation in uterine SMC and may influence tissue remodelling and reconstruction during physiological and pathophysiological events.
-smooth muscle actin/heparin/mast cells/myometrium and leiomyoma/p27
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