Platelet derived serotonin drives the activation of rat cardiac fibroblasts by 5-HT2A receptors.
Platelet activation occurs in different acute and chronic heart diseases including myocardial infarction, obstructive hypertrophic cardiomyopathy and valve stenosis. Recent studies suggested that some factors secreted by activated platelets may participate in cardiac remodeling. In the present study, we investigated whether platelets and platelet-released serotonin (5-HT) are directly involved in the functional regulation of cardiac fibroblasts. Treatment of neonatal rat cardiac fibroblasts with platelet lysate, 5-HT and the 5-HT2A receptor agonist DOI increased the expression of alpha-SMA protein, a marker of fibroblast differentiation into myofibroblasts. Platelet lysate, 5-HT and DOI also induced a time-dependent stimulation of cardiac fibroblast migration that was inhibited by the 5-HT2A receptor antagonist ketanserin. Finally, incubation of cardiac fibroblasts with platelet lysate or 5-HT enhanced secretion of TGF-beta1 and expression of MMP-3 and MMP-13. As observed for fibroblast migration, these effects were prevented by ketanserin. These results demonstrated for the first time that factors released from platelet directly regulate cardiac fibroblasts by enhancing secretion of TGF-beta1 and MMPs and promoting their migration and differentiation. 5-HT released by platelets appears to be a major contributor of platelet effects which are mediated through 5-HT2A receptors.
Yabanoglu
Samiye
S
Institut National de la Santé et de la Recherche Médicale U858, Institut de Médecine Moléculaire de Rangueil, Bât L3, CHU Rangueil, Toulouse cedex 4, France.
Akkiki
Mansour
M
Seguelas
Marie-Helène
MH
Mialet-Perez
Jeanne
J
Parini
Angelo
A
Pizzinat
Nathalie
N
D000199:Actins / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat