Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation

Abstract

Kardiovaskularne bolesti predstavljaju najveći uzrok smrtnosti ljudske populacije, a jedna od njihovih najučestalijih patoloških komponenti je i sama ateroskleroza. Proliferacija ili deoba glatkih mišićnih ćelija krvnih sudova (VSMC) ključni je događaj u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. U procesu diferencijacije i abnormalne deobe VSMC povezanih sa hipertenzijom i aterosklerozom uključen je i trombin. Stimulisanje VSMC trombinom dovodi do aktivacije ekstracelularnim signalima regulisanih kinaza 1 i 2 (ERK1/2), preko transaktivacije receptora za epidermalni faktor rasta (EGFR). U našim ranijim studijama potvrdili smo na osnovu inhibicije ERK1/2 od strane PD9805 inhibitora, učešće ERK1/2 u regulaciji proliferacije VSMC izazvanoj trombinom. Takođe, protein kinaza C delta (PKCδ), detektovana je u VSMC i pokazano je da je i njena aktivnost takođe regulisana trombinom. U okviru ovog preglednog članka biće prikazani literaturni podaci koji se odnose na ulogu PKCδ i ERK1/2, u posredovanju proliferativnog efekta trombina na VSMC.

Cardiovascular disease is the greatestest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. Thrombin is involved in the differentiation and abnormal proliferation of VSMC associated with atherosclerosis and hypertension. Thrombin stimulation results in extracellular signal-regulated kinase (ERK1/2) activation through transactivation of the epidermal growth factor receptor (EGFR). Based on our reacent studies in which PD98059 used to inhibit ERK1/2, we have shown previously that ERK1/2 was involved in the regulation by thrombin of VSMC’s proliferation. In addition, protein kinase C delta (PKCδ) have also been detected in VSMC and shown to be regulated by thrombin. In this review, we are presenting literature data relating to role of PKCδ and ERK1/2 in mediating the mitogenic action of thrombin in VSMC.