Serotonin and thromboxane A2 stimulate platelet-derived microparticle-induced smooth muscle cell proliferation.
BACKGROUND
At the sites of vascular injury, activated and aggregating platelets release small vesiculated structures called platelet microparticles (PMPs). Apart from PMPs they also release several vasoactive mediators including serotonin and thromboxane A2 (TXA2). PMPs, serotonin, and TXA2 have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Thus, this study is designed to examine the interaction between PMPs and serotonin or TXA2 in inducing rabbit VSMC proliferation.


METHODS
Growth-arrested rabbit SMCs were incubated in serum-free medium with different concentrations of PMPs with or without serotonin or TXA2. VSMC proliferation was examined by increase in incorporation of [3H]thymidine into DNA and by increase in cell number.


RESULTS
PMPs stimulated DNA synthesis in a dose-dependent manner; up to an added concentration of 30 microg/ml (1489 +/- 90%) they stimulated SMC proliferation in a logarithmic fashion. Serotonin at 50 microM (345 +/- 21%) and TXA2 at 7.5 microM (900 +/- 36%) had their maximal effect. When added together, PMPs (10 microg/ml) and serotonin (5 microM), synergistically induced DNA synthesis (581 +/- 36% and 211 +/- 11% when added alone and 1201 +/- 95% when added together), whereas PMPs (10 microg/ml) and TXA2 (5 microM) additively induced DNA synthesis (581 +/- 36% and 781 +/- 56% when added alone and 1262 +/- 115% when added together). These increases in DNA synthesis were paralleled by increase in cell number.


CONCLUSIONS
PMPs, serotonin, and TXA2 are mitogenic to SMC, and function as amplification factors to each other, suggesting that inhibition of neointimal proliferation after vascular injury may require the combined use of multiple growth factor inhibitors to simultaneously block several critical cellular activation pathways.
Department of Internal Medicine, Division of Cardiology, University of Texas Health Science Center Medical School, Houston, TX 77030, USA. rajbabu.pakala@medstar.net
Rajbabu
R
Pakala
D000818:Animals; D001792:Blood Platelets; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D010316:Particle Size; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology*
D012701:Serotonin; D013928:Thromboxane A2