TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Resanović, I.
AU  - Savić, Kristina
AU  - Jovanović, A.
AU  - Zafirović, S.
AU  - Obradović, Milan
AU  - Isenović, E. R.
PY  - 2013
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6449
AB  - Zajednički činilac u nastanku vaskularnih oboljenja kao što su ateroskleroza, restenoza i hipertenzija je patološka proliferacija i akumulacija glatkih mišićnih ćelija krvnog suda (VSMC) u njegov unutrašnji (intima) sloj.  Trombin, ključni hormon koagulacionoaterogenetske mreže posreduje u regulisanju tonusa i propustljivosti krvnih sudova, migracije i proliferacije VSMC, privlačenja monocita i raznih proinflamatornih markera u aterosklerotske lezije i svoje efekte ostvaruje direktno kao serinska proteinaza i aktivacijom svojih receptora spregnutih sa G proteinom (GPCR). Pokazano je da trombin posreduje u proliferaciji VSMC transaktivacijom receptora za epidermalni faktor rasta (EGFR). Proces transaktivacije EGFR preko aktivacije trombinskih receptora, uključuje metaloproteinaze koje generišu ligande proteolitičkim cepanjem membranskih prekursora, kao što je heparin vezujući epidermalni faktor rasta (HB-EGF) koji se vezuje za EGFR i aktivira ga, što vodi proliferaciji VSMC preko nishodnih, signalnih puteva mitogenom aktiviranih protein kinaza (MAPK).  U okviru ovog preglednog članka su prikazani i diskutovani novi literaturni podaci koji se odnose na: ulogu aktivacije EGFR u posredovanju proliferativnog efekta trombina na VSMC, razumevanje i reviziju koncepta trostruke kaskade transaktivacije EGFR stimulisane trombinom u mehanizmu proliferacije VSMC.
AB  - The common factor in the development of
vascular diseases, such as atherosclerosis,
hypertension and restenosis, is excessive accumulation
and proliferation of vascular smooth muscle cells
(VSMC) within inner (intima) layer of vessel wall.
 Thrombin, a key player in athero-coagulation
maze, mediates the regulation of vascular permeability
and contraction, migration and proliferation of VSMC,
attracting monocytes and a variety of proinflammatory markers in atherosclerotic lesions.
Thrombin exerts its effects either directly as serine
proteinases and/or via activation of its G proteins
coupled receptors (GPCR). It has been shown that
thrombin mediates transactivation of epidermal growth
factor receptor (EGFR) within the process of VSMC
proliferation. EGFR transactivation process through
the activation of thrombin protease activated receptor
(PAR), includes a matrix metalloproteinase cleavage of
membrane ligands precursors such as epidermal
growth factor like growth factor that binds heparin
(HB-EGF) that binds to the EGFR and activates it,
leading to VSMC proliferation via downstream
signaling pathways of mitogen activated protein kinase
(MAPK).
 This review article presents review of the new
literature data concerning: the role of EGFR
activation in mediating the proliferative effect of
thrombin in VSMC and understanding of the concept of
the triple cascade of EGFR transactivation stimulated
by thrombin in the mechanism of VSMC proliferation.
PB  - Univerzitet u Beogradu - Medicinski fakultet
T2  - Medicinska Istraživanja
T1  - Role of the epidermal growth factor receptor in thrombin regulated vascular smooth muscle cells proliferation
T1  - Uloga receptora za epidermalni faktor rasta u trombinom regulisanoj proliferaciji glatkih mišićnih ćelija krvnih sudova
VL  - 47
IS  - 1
SP  - 10
EP  - 20
DO  - 10.5937/MedIst1301005S
ER  - 

@article{
author = "Smiljanić, Katarina and Resanović, I. and Savić, Kristina and Jovanović, A. and Zafirović, S. and Obradović, Milan and Isenović, E. R.",
year = "2013",
abstract = "Zajednički činilac u nastanku vaskularnih oboljenja kao što su ateroskleroza, restenoza i hipertenzija je patološka proliferacija i akumulacija glatkih mišićnih ćelija krvnog suda (VSMC) u njegov unutrašnji (intima) sloj.  Trombin, ključni hormon koagulacionoaterogenetske mreže posreduje u regulisanju tonusa i propustljivosti krvnih sudova, migracije i proliferacije VSMC, privlačenja monocita i raznih proinflamatornih markera u aterosklerotske lezije i svoje efekte ostvaruje direktno kao serinska proteinaza i aktivacijom svojih receptora spregnutih sa G proteinom (GPCR). Pokazano je da trombin posreduje u proliferaciji VSMC transaktivacijom receptora za epidermalni faktor rasta (EGFR). Proces transaktivacije EGFR preko aktivacije trombinskih receptora, uključuje metaloproteinaze koje generišu ligande proteolitičkim cepanjem membranskih prekursora, kao što je heparin vezujući epidermalni faktor rasta (HB-EGF) koji se vezuje za EGFR i aktivira ga, što vodi proliferaciji VSMC preko nishodnih, signalnih puteva mitogenom aktiviranih protein kinaza (MAPK).  U okviru ovog preglednog članka su prikazani i diskutovani novi literaturni podaci koji se odnose na: ulogu aktivacije EGFR u posredovanju proliferativnog efekta trombina na VSMC, razumevanje i reviziju koncepta trostruke kaskade transaktivacije EGFR stimulisane trombinom u mehanizmu proliferacije VSMC., The common factor in the development of
vascular diseases, such as atherosclerosis,
hypertension and restenosis, is excessive accumulation
and proliferation of vascular smooth muscle cells
(VSMC) within inner (intima) layer of vessel wall.
 Thrombin, a key player in athero-coagulation
maze, mediates the regulation of vascular permeability
and contraction, migration and proliferation of VSMC,
attracting monocytes and a variety of proinflammatory markers in atherosclerotic lesions.
Thrombin exerts its effects either directly as serine
proteinases and/or via activation of its G proteins
coupled receptors (GPCR). It has been shown that
thrombin mediates transactivation of epidermal growth
factor receptor (EGFR) within the process of VSMC
proliferation. EGFR transactivation process through
the activation of thrombin protease activated receptor
(PAR), includes a matrix metalloproteinase cleavage of
membrane ligands precursors such as epidermal
growth factor like growth factor that binds heparin
(HB-EGF) that binds to the EGFR and activates it,
leading to VSMC proliferation via downstream
signaling pathways of mitogen activated protein kinase
(MAPK).
 This review article presents review of the new
literature data concerning: the role of EGFR
activation in mediating the proliferative effect of
thrombin in VSMC and understanding of the concept of
the triple cascade of EGFR transactivation stimulated
by thrombin in the mechanism of VSMC proliferation.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet",
journal = "Medicinska Istraživanja",
title = "Role of the epidermal growth factor receptor in thrombin regulated vascular smooth muscle cells proliferation, Uloga receptora za epidermalni faktor rasta u trombinom regulisanoj proliferaciji glatkih mišićnih ćelija krvnih sudova",
volume = "47",
number = "1",
pages = "10-20",
doi = "10.5937/MedIst1301005S"
}

Smiljanić, K., Resanović, I., Savić, K., Jovanović, A., Zafirović, S., Obradović, M.,& Isenović, E. R.. (2013). Role of the epidermal growth factor receptor in thrombin regulated vascular smooth muscle cells proliferation. in Medicinska Istraživanja
Univerzitet u Beogradu - Medicinski fakultet., 47(1), 10-20.
https://doi.org/10.5937/MedIst1301005S

Smiljanić K, Resanović I, Savić K, Jovanović A, Zafirović S, Obradović M, Isenović ER. Role of the epidermal growth factor receptor in thrombin regulated vascular smooth muscle cells proliferation. in Medicinska Istraživanja. 2013;47(1):10-20.
doi:10.5937/MedIst1301005S .

Smiljanić, Katarina, Resanović, I., Savić, Kristina, Jovanović, A., Zafirović, S., Obradović, Milan, Isenović, E. R., "Role of the epidermal growth factor receptor in thrombin regulated vascular smooth muscle cells proliferation" in Medicinska Istraživanja, 47, no. 1 (2013):10-20,
https://doi.org/10.5937/MedIst1301005S . .

TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Savić, Kristina
AU  - Obradovic, Milan
AU  - Putniković, Biljana
AU  - Đorđević, Jelena
AU  - Isenović, Esma
PY  - 2013
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6448
AB  - 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.
AB  - 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.
PB  - Univerzitet u Beogradu - Medicinski fakultet
T2  - Medicinska Istraživanja
T1  - Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation
T1  - Uloga PKCd i ERK1/2 u trombinom stimulisanoj proliferaciji glatkih mišićnih ćelija krvnih sudova
VL  - 47
IS  - 1
SP  - 5
EP  - 9
DO  - 10.5937/MedIst1301005S
ER  - 

@article{
author = "Smiljanić, Katarina and Savić, Kristina and Obradovic, Milan and Putniković, Biljana and Đorđević, Jelena and Isenović, Esma",
year = "2013",
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.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet",
journal = "Medicinska Istraživanja",
title = "Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation, Uloga PKCd i ERK1/2 u trombinom stimulisanoj proliferaciji glatkih mišićnih ćelija krvnih sudova",
volume = "47",
number = "1",
pages = "5-9",
doi = "10.5937/MedIst1301005S"
}

Smiljanić, K., Savić, K., Obradovic, M., Putniković, B., Đorđević, J.,& Isenović, E.. (2013). Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation. in Medicinska Istraživanja
Univerzitet u Beogradu - Medicinski fakultet., 47(1), 5-9.
https://doi.org/10.5937/MedIst1301005S

Smiljanić K, Savić K, Obradovic M, Putniković B, Đorđević J, Isenović E. Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation. in Medicinska Istraživanja. 2013;47(1):5-9.
doi:10.5937/MedIst1301005S .

Smiljanić, Katarina, Savić, Kristina, Obradovic, Milan, Putniković, Biljana, Đorđević, Jelena, Isenović, Esma, "Role Of Pkc-delta And Erk1/2 In Trombin stimulated vascular smooth muscle cells proliferation" in Medicinska Istraživanja, 47, no. 1 (2013):5-9,
https://doi.org/10.5937/MedIst1301005S . .