(Hypertension. 2000;35:978.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Angiotensin II and 
vß3 Integrin Expression in Rat Neonatal Cardiac Fibroblasts
From the Division of Endocrinology, Diabetes and Hypertension (W.A.H., R.E.L.), University of California Los Angeles, School of Medicine, and the Department of Medicine/Cardiology (K.G., M.N., P.S., E.F.), Charité, Campus Virchow Klinikum, Humboldt Universität Berlin and Deutsches Herzzentrum Berlin, Berlin, Germany.
Correspondence to Dr Kristof Graf, Med Klinik m S Kardiologie, Charité, Campus Virchow Klinikum, Humboldt Universität Berlin und Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Abstract—We recently
demonstrated that 
vß3 integrins are
involved in the mechanisms of angiotensin II (Ang
II)–induced DNA synthesis and collagen gel contractions in rat cardiac
fibroblasts (CFBs), cellular mechanisms that are relevant for cardiac
remodeling. The aim of the present study was to elucidate the
effect of Ang II and other growth factors on the regulation of the
vß3 integrins in fibroblasts from neonatal
rat hearts. The vß3 integrin receptor
expression was significantly increased (P<0.05) at the
mRNA level after treatment with Ang II, transforming growth
factor-ß1 (TGF-ß1), and
platelet-derived growth factor (PDGF) for 8 and 16 hours. The
surface expression of the v and ß3
integrin subunits was elevated after 32 and 48 hours
(P<0.05) as determined with flow cytometry. To
investigate fibroblast motility, we performed chemotaxis experiments
with transwell chambers. Ang II was chemotactic for CFBs, as tested
with checkerboard experiments. The chemotactic effect was concentration
dependent and was completely blocked by Ang II type 1
receptor blockers but not by Ang II type 2 receptor blocker
PD 123319. Ang II– and PDGF-BB–mediated chemotaxis could be
significantly inhibited by RGD peptides and the blocking antibodies
against vß3 integrin (both
P<0.01). Adhesion of CFBs to vitronectin
was partially inhibited by an antibody to
vß3 integrin but was mainly mediated by an
vß5 integrin. Relevant in vivo expression
of vß3 integrin by CFBs was confirmed with
in situ hybridization with probes for v and
ß3 mRNA in rat hearts. The present study demonstrates
that the expression of vß3 integrin is
augmented by Ang II, PDGF, and TGF-ß1 in neonatal CFBs.
Furthermore, this integrin is involved in the chemotaxis, motility, and
adhesion of CFBs. The present findings support the current concept
that integrins participate in the control of fibroblast behavior during
cardiac remodeling mechanisms.
Key Words: integrins • angiotensin II • fibroblasts • remodeling
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