Molecular mechanisms of ATP and insulin synergistic stimulation of coronary artery smooth muscle growth

1  Department of Pharmacology, 2  Molecular Biology Program, and 3  Food for the 21st Century Nutrition Program, University of Missouri, Columbia, Missouri 65212 Coronary artery disease (CAD) is the major cause of death in diabetics. Abnormal proliferation of coronary artery smooth muscle cells (CAS...

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Published in:American journal of physiology. Heart and circulatory physiology 2001-02, Vol.280 (2), p.H795-H801
Main Authors: Agazie, Yehenew M, Bagot, J. Courtney, Trickey, Erica, Halenda, Stephen P, Wilden, Peter A
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Animals
Cell Division - drug effects
Cells, Cultured
Coronary Vessels - cytology
Coronary Vessels - drug effects
Coronary Vessels - enzymology
Drug Synergism
Enzyme Inhibitors - pharmacology
Extracellular Space - metabolism
Flavonoids - pharmacology
Hypoglycemic Agents - pharmacology
Insulin - pharmacology
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Mitogen-Activated Protein Kinases - metabolism
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - enzymology
Phosphorylation
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-raf - metabolism
ras Proteins - metabolism
Swine
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Summary:1  Department of Pharmacology, 2  Molecular Biology Program, and 3  Food for the 21st Century Nutrition Program, University of Missouri, Columbia, Missouri 65212 Coronary artery disease (CAD) is the major cause of death in diabetics. Abnormal proliferation of coronary artery smooth muscle cells (CASMC) leads to intimal thickening in CAD. We examined signaling mechanisms involved in the mitogenic effect of ATP and insulin on CASMC. ATP and insulin individually stimulated DNA synthesis by 4- and 2-fold, respectively; however, they acted synergistically to stimulate an increase of 17-fold over basal. A similar synergistic stimulation of extracellular signal-regulated kinase (ERK) and mitogen-activated protein or ERK kinase activities was observed (ATP, 7-fold; insulin, 2-fold; and ATP + insulin, 16-fold over basal). However, the combination of ATP and insulin stimulated only an additive activation of Raf (ATP, 5-fold; insulin,
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.2001.280.2.h795