Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor (PDGF).
This experiment was designed to investigate the possible involvement of angiotensin II (Ang II) and platelet-derived growth factor (PDGF) in the mechanism underlying stretch-induced proliferation of vascular smooth muscle cells (SMCs). SMCs from the rabbit aortic media were grown on polystyrene rubber-bottomed dishes coated with type I collagen. Cells were stretched cyclically by a vacuum-operated downward flexion of the culture dish bottom. A 1.4- to 1.6-fold increase in proliferation of SMCs was induced by cyclic stretching, as determined by [3H]-thymidine incorporation, in a stretch force-dependent manner in the range of 5% to 15% elongation, 30 cycles/min for 24 h. Expression of PDGF-B chain mRNA was up-regulated in a time-dependent manner in the range of 2 to 24 h, 10% elongation, and 30 cycles/min. Saralasin, a selective antagonist of Ang II, and captopril, an angiotensin I converting enzyme inhibitor, significantly suppressed the stretch-induced proliferation of SMCs. Blockade of angiotensinogen mRNA translation by antisense oligonucleotide inhibited proliferation under the mechanical strain. Stretch-induced proliferation was inhibited by 78% in the presence of anti-PDGF-AB neutralizing antibody. Increased expression of PDGF-B chain mRNA under the mechanical strain was inhibited by treatment with saralasin. Our results indicate that the stretch-induced proliferation of cultured SMCs is mediated at least in part via increased production of Ang II by the local renin-angiotensin system and a subsequent up-regulation of PDGF-B chain mRNA in an autocrine-paracrine manner.
Li
Q
Q
Department of Pathology, Wakayama Medical College, Japan.
Muragaki
Y
Y
Ueno
H
H
Ooshima
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002216:Captopril / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D000806:Angiotensin-Converting Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D000808:Angiotensinogen; D002216:Captopril; D012504:Saralasin; D013936:Thymidine