Responsiveness to growth factors in aortic vascular smooth muscle cells from rats with cirrhosis.
Hemodynamic changes in cirrhosis may be associated with alterations in aortic vascular smooth muscle cell (AVSMC) function. The present study compared the proliferative response to serum and growth factors in cirrhotic and control AVSMC. Serum from cirrhotic rats, cirrhotic cell lysates, and the conditioned medium of cultured cirrhotic AVSMC induced an increase in [3H]thymidine incorporation in control but not in cirrhotic AVSMC. Platelet-derived growth factor-beta (PDGF-BB) induced a greater increase in [3H]thymidine incorporation in cirrhotic than in control cells. [3H]thymidine incorporation induced by cirrhotic conditioned medium was blocked by anti-PDGF antibody. Immunoblot studies showed that the anti-PDGF antibody recognized a 30-kDa protein in the conditioned medium of cirrhotic AVSMC culture, a protein corresponding to PDGF. Binding studies of PDGF-BB indicated a twofold increase in receptor density in cirrhotic AVSMC with no alteration in affinity for PDGF-BB. We conclude that an increased responsiveness of cirrhotic AVSMC to the PDGF could contribute to alterations in AVSMC and muscle cell tone that may play a role in the hemodynamic changes in cirrhosis.
Tazi
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KA
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Beaujon, Clichy, France.
Trombino
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C
Moreau
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R
Lebrec
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D
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007700:Kinetics; D008106:Liver Cirrhosis, Experimental / Q000097:blood* / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D013936:Thymidine