Short-term stimulation of vascular smooth muscle cells with platelet-derived growth factor (PDGF)-BB and angiotensin II induces.
Growth factors such as the platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II) have been shown to induce vascular smooth muscle cell (VSMC) proliferation after long stimulation periods. Little is known though, about the effects of PDGF-BB and Ang II on VSMC proliferation after short stimulation periods. The purpose of our study was to examine whether a short term (3-60 min) stimulation of VSMC with PDGF-BB or Ang II is sufficient to induce cell proliferation. Incubation of VSMC with Ang II (100 nM) or PDGF-BB (50 ng/ml) caused a significant increase in [3H]thymidine incorporation starting after a 3-min stimulation, while the cell counts required 32 and 8 h of stimulation, respectively. Mitogen-activated protein kinase activation reached a maximum at 5-10 min of PDGF-BB or Ang II stimulation. This study demonstrates that the growth-promoting effects of PDGF-BB and Ang II are strongly dependent on the length of the stimulation period and that while prolonged stimulation periods (>8-32 h) result in VSMC proliferation, short ones (3-60 min) result only in [3H]thymidine incorporation without an increase in cell count, a fact of considerable pathophysiological significance, considering that the time kinetics of growth factors in the VSMC microenvironment have not as yet been clarified.
Gouni-Berthold
I
I
Medizinische Universitäts-Poliklinik Bonn, Germany.
Berthold
H K
HK
Seewald
S
S
Seul
C
C
Ko
Y
Y
Vetter
H
H
Sachinidis
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011921:Rats, Inbred WKY; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014316:Tritium; D000804:Angiotensin II; D000077214:Becaplermin; D004247:DNA; D013936:Thymidine