J Korean Soc Transplant.  2003 Dec;17(2):121-125.

Effects of Carvedilol on PDGF-induced Collagen Synthesis and Signal Transduction in Rat Vascular Smooth Muscle Cell

• Park J
• Huh KH
• Ha H
• Kim MS
• Kim YS
• Park K
• Chung KY

Abstract

PURPOSE
Proliferation, migration, and the accumulation of extracellular matrix (ECM) protein of vascular smooth muscle cells (VSMC) play roles for transplant arteriosclerosis. We have previously reported that carvedilol (CA) inhibits the proliferation and the migration of VSMCs. The present study examined the effects of CA on platelet-derived growth factor (PDGF)-induced collagen synthesis in VSMC and the roles of reactive oxygen species (ROS), extracellular signal- regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK).
METHODS
Primary cultured rat VSMCs were obtained from aorta of Sprague-Dawley rats. Growth arrested and synchronized cells were pretreated with CA (10 nM~10micrometer) at 1 hour before the addition of PDGF 10 ng/ml. Collagen synthesis was measured by 3[H]-proline incorporation, ROS by flow cytometry using ROS-sensitivedichlorofluorescein (DCF) dye, and the activation of ERK andp38 MAPK by Western blot analysis.
RESULTS
PDGF significantly increased collagen synthesis by 2.0-fold, intracellular ROS by 1.6-fold, the activation of ERK 1/2 and p38 MAPK by 4.2-fold and 3.9-fold compared to control, respectively. CA above 1micrometer inhibited PDGF-induced collagen synthesis. CA also inhibited DCF-sensitive ROS and the activation of ERK and p38 MAPK. All pharmacological inhibitors of ROS, ERK, and p38 MAPK effectively inhibited PDGF-induced collagen synthesis.
CONCLUSION
These data suggest that CA inhibit PDGF-induced collagen synthesis possibly through inhibiting intracellular ROS and ERK 1/2 and p38 MAPK activation.

Keyword

Carvedilol; Collagen; Vascular smooth muscle cell; Reactive oxygen species; Mitogen-activated protein kinase

MeSH Terms

Animals
Aorta
Arteriosclerosis
Blotting, Western
Collagen*
Extracellular Matrix
Flow Cytometry
Muscle, Smooth, Vascular*
p38 Mitogen-Activated Protein Kinases
Platelet-Derived Growth Factor
Protein Kinases
Rats*
Rats, Sprague-Dawley
Reactive Oxygen Species
Signal Transduction*
Collagen
Platelet-Derived Growth Factor
Protein Kinases
Reactive Oxygen Species
p38 Mitogen-Activated Protein Kinases