Angiotensin ii secretion and bfgf expression in microvascular
endothelial cells and ventricular myocytes from adult rat hearts.
Fischer, Thomas A., Dan Ungureanu-Longrois, Krishna Singh, Juan De
Zengotita, Daniel Deugarte, Alborz Alali, Albert P. Gadbut, Min-Ae
Lee, Jean-Luc Balligand, Imre Kifor, Thomas W. Smith, and Ralph A.
Kelly.
Cardiovascular Division, and Division of Endocrinology and
Hypertension, Department of Medicine, Brigham and Women's Hospital
and Harvard Medical School, Boston, MA
APStracts 3:0467H, 1996.
Basic fibroblast growth factor (bFGF; FGF-2) and angiotensin II (AII),
among other peptide signaling autacoids (cytokines), are known to
regulate the phenotypic adaptation of cardiac muscle to physiologic
stress. The cell type(s) in cardiac muscle responsible for AII
synthesis and secretion, and the role of endogenous cytokines in the
regulation of bFGF induction, remain unclear. Using confluent, serum
-starved, low passage cultures of cardiac microvascular endothelial
cells (CMEC), AII could be detected in cellular lysates and in medium
conditioned by these cells by HPLC followed by radioimmunoassay for
AII. Using a cell blot assay technique, the secretion of angiotensins
by individual CMEC could be detected. AII secretion was decreased by
brefeldin A, an agent that interrupts constitutive and regulated
secretory pathways for peptide autacoid/hormone synthesis, suggesting
de novo synthesis, activation and secretion of angiotensins by CMEC.
In primary isolates of adult rat ventricular myocytes (ARVM) and
CMEC, AII, acting at AT1 receptors in both cell types, was found to
increase bFGF mRNA levels measured by RNase protection assay.
Endothelin-1 (ET-1), which is known to be synthesized by CMEC, and
bFGF itself, which has been detected in both ARVM and CMEC, increased
bFGF transcript levels in both cell types. Interleukin-1[beta] (IL
-1[beta]), which like AII and ET-1 is known to activate mitogen
-activated protein kinases in both ARVM and CMEC, increased bFGF mRNA
levels only in cardiac myocytes. Thus, cytokines such as AII, ET-1,
bFGF and IL-1[beta] locally generated by cellular constituents of
cardiac muscle, including CMEC, regulate bFGF mRNA levels in a cell
type-specific manner.
Received 13 December 1995; accepted in final form 6 November
1996.
APS Manuscript Number H1160-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996