March 14, 2000Circulation
Angiotensin II Has Multiple Profibrotic Effects in Human Cardiac Fibroblasts
Key result
Angiotensin II increased DNA synthesis 5-fold (P<0.01) and stimulated a 2-fold increase in TGF-beta1, laminin, and fibronectin mRNA levels in human cardiac fibroblasts via the AT1 receptor.
Why the study?
Does Angiotensin II promote profibrotic effects in human cardiac fibroblasts?
Population
Fibroblasts isolated from ventricles of explanted human hearts (n=13 human ventricles)
Comparison
Angiotensin II alone or in the presence of… vs Untreated cells or Angiotensin II alone versus…
Design
Preclinical
Follow-up
up to 24 hours (in vitro)
Authors
Discussion
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Member takes
Implication
Supports AT1-mediated profibrotic signaling in human fibroblasts; hypothesis-generating for remodeling therapies pending in vivo validation.
Structured PICO
Does Angiotensin II promote profibrotic effects in human cardiac fibroblasts?
P
Population
Fibroblasts isolated from ventricles of explanted human hearts (n=13 human ventricles)
I
Intervention
Angiotensin II (100 nmol/L) alone or in the presence of irbesartan (10 micromol/L), PD 123319 (10 micromol/L), or divalinil (100 nmol/L)
C
Comparator
Untreated cells or Angiotensin II alone versus Angiotensin II plus receptor antagonists
O
Outcome
Cellular growth, extracellular matrix accumulation, and adhesion (including DNA synthesis, TGF-beta1 mRNA, laminin, fibronectin, and PAI-1 expression)surrogate
Main Result
Effect estimate: 5-fold increase in DNA synthesis
p-value: p=<0.01
Angiotensin II promotes fibrosis in human cardiac fibroblasts via the AT1 receptor by stimulating growth, extracellular matrix accumulation, and adhesion, providing mechanistic insight into cardiac remodeling.
Cite This Study
Kawano et al. (2000) studied Heart failure (n=13). Angiotensin II vs. Irbesartan, PD 123319, or divalinil was evaluated on DNA synthesis and profibrotic marker mRNA levels (5-fold increase in DNA synthesis, p=<0.01). Angiotensin II increased DNA synthesis 5-fold (P<0.01) and stimulated a 2-fold increase in TGF-beta1, laminin, and fibronectin mRNA levels in human cardiac fibroblasts via the AT1 receptor.