Vol. 273, Issue 4, G883-G890, October 1997
Responsiveness to growth factors in aortic vascular smooth
muscle cells from rats with cirrhosis
Khalid A.
Tazi,
Concetta
Trombino,
Richard
Moreau, and
Didier
Lebrec
Laboratoire d'Hémodynamique Splanchnique et de Biologie
Vasculaire, Unité de Recherches de Physiopathologie
Hépatique, Institut National de la Santé et de la
Recherche Médicale, Hôpital Beaujon, 92118 Clichy, France
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-
(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.
platelet-derived growth factor; fibroblast growth factor; hemodynamic changes
