Premium
N Inhibitory Effect of Hsp70 on Angiotensin II‐Induced Vascular Smooth Muscle Cell Hypertrophy
Author(s) -
ZHENG YING,
IM CHANG NIM,
KIM SUN HYE,
HUANG TAIQIN,
LI JINFENG,
SEO JEONG SUN
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a546-b
Subject(s) - vascular smooth muscle , hsp70 , muscle hypertrophy , angiotensin ii , dephosphorylation , mapk/erk pathway , heat shock protein , western blot , medicine , endocrinology , chemistry , kinase , biology , microbiology and biotechnology , phosphatase , phosphorylation , biochemistry , smooth muscle , gene , blood pressure
Angiotensin II (Ang II) induces hypertrophy of adult rat vascular smooth muscle cells (VSMCs) via activation of a complex series of intracellular signaling events. Hsp70, which is a representative heat shock protein, is known to be induced by various stimuli in cardiovascular system, and has protective effect in cardiovascular diseases. In this study, we attempted to determine whether Hsp70 can protect VSMC from Ang II‐induced hypertrophy. VSMCs were obtained by primary culture from rat thoracic aorta. To alter the expression level of Hsp70, we applied Hsp70 gene overexpression, heat treatment and Hsp70 siRNA in the experiment. [3H]‐leucine incorporation was used to assess VSMC hypertrophy and western blot analysis was used to determine the effective signal molecules. Our results showed that Hsp70 overexpression inhibited Ang II‐induced VSMC hypertrophy. Both heat treatment and Hsp70 overexpression inhibited Ang II‐induced ERK1/2 activation, while Hsp70 siRNA slightly increased ERK1/2 activation. However, Activity of MEK1/2 was not affected. Hsp70 overexpression significantly increased MKP (MAP kinase phosphatase)‐1 expression, which can inactivate ERK 1/2 by dephosphorylation. Conversly, Hsp70 siRNA blocked MKP‐1 expression completely. In conclusion, pre‐induction or overexpression of Hsp70 can protect VSMC from Ang II‐induced hypertrophy through ERK 1/2 inactivation by MKP‐1. Hence, there is a good prospect that Hsp70 may have inhibitory effect on vascular hypertrophy.