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Clin Cardiol J Volume 1 | Issue 1
December 04-05, 2017 Dallas, USA
International Conference on
Heart Congress, Vascular Biology and Surgeon’s Meeting
Fluvastatin inhibits AGE-induced cell proliferation, migration, and ECM accumulation
in VSMC by targeting CTGF
Young Jin Kang
Yeungnam University, South Korea
Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is implicated in fibroblast
proliferation, cellular adhesion, angiogenesis and extracellular matrix (ECM) synthesis. Recent studies have
demonstrated that advanced glycation end products (AGE) and their receptor-ligand interactions play a key role
in neointimal formation and renal fibrosis after vascular injury. However, the potential link between CTGF and
AGE has not been investigated. Based on this, we aimed to examine whether Fluvastatin could protect AGE
induced vascular smooth muscle cell (VSMC) fibrosis and its putative transduction signals. In the present study,
we have shown that AGE stimulated CTGF mRNA and protein expression time-dependent manners. The CTGF
induction signal mediated by AGE was demonstrated via ERK1/2, JNK, and Egr-1 but not p38, consequently
cell proliferation, migration, and ECM accumulation were regulated by CTGF signal pathway. And AGE also
stimulated VSMC proliferation, migration, and ECM accumulations were blocked by Fluvastatin. In addition, the
inhibitory effect of Fluvastatin was restored by administration of CTGF recombinant protein. Furthermore, AGE-
induced VSMC proliferation was dependent on cell cycle arrest, increasing G1/G0 phase. Fluvastatin repressed
cell cycle regulatory genes, cyclin D1 and CDK4 and augmented cyclin-dependent kinase inhibitors, p27 and p21
in AGE-induced VSMC. Taken together, Fluvastatin suppressed AGE-induced VSMC proliferation, migration,
and ECM accumulation in by targeting CTGF signaling mechanism. Therefore, it might be recent evidence for
CTGF as a potential therapeutic target in diabetic vasculature complication.
Biography
Young Jin Kang has completed her PhD degree from Gyeongsang National University in 2000 and she is working at Yeongnam University since 2005 as
a Professor. Her major subject is what kind of signal gene regulates vascular fibrosis and how to modulate vascular smooth muscle cell proliferation in
diabetes or hypertension?