Medial and endothelial platelet-derived growth factor A chain expression is regulated by in vivo exposure to elevated flow.
Previous work from this laboratory demonstrated that in vivo exposure to elevated arterial flow stimulates endothelial and smooth muscle cell hyperplasia concomitant with lumen enlargement, medial wall hypertrophy, and increases in medial extracellular connective tissue in rat mesenteric small arteries. In an effort to elucidate the role of growth factors in mediating this arterial remodeling response, in situ hybridization was performed on control and high flow arterial sections using 35S-labeled riboprobes for PDGF-A, PDGF-B, basic FGF, and TGFbeta1 mRNA. Results demonstrate that after exposure to elevated arterial flow for 24 h, expression of PDGF-A mRNA in the media was significantly elevated over basal levels (+215%, p < 0.001). This expression decreased towards control levels by 3 and 7 days. Increased endothelial expression of PDGF-A mRNA over basal levels was evident after 3 and 7 days of elevated flow (+129%, p < 0.01; +182%; p < 0.01, respectively). Acute medial PDGF-A mRNA expression may result from elevated circumferential hoop stress secondary to flow-induced dilation while delayed expression in the endothelium may result from normalization of wall shear stress. Endothelial expression of PDGF-B mRNA was significantly elevated over control levels (+62%, p < 0.01) after exposure to high flow for 7 days. Expression of bFGF and TGFbeta1 mRNA was not significantly different between control and high flow vessels at all times measured. These results suggest a role for PDGF-A in regulating acute arterial remodeling following in vivo exposure to elevated flow.
Tulis
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Department of Physiology, Eastern Virginia Medical School, Norfolk, Va., 23501-1980 USA.
Prewitt
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D000818:Animals; D001345:Autoradiography; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression; D018056:Hemorheology; D006965:Hyperplasia; D008432:Mathematical Computing; D008638:Mesenteric Arteries / Q000473:pathology / Q000502:physiology*; D008955:Models, Cardiovascular; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2