Oleic acid enhances vascular smooth muscle cell proliferation via phosphatidylinositol 3-kinase/Akt signaling pathway.
Nonesterified fatty acids are acutely liberated during lipolysis and are chronically elevated in pathological conditions such as insulin resistance, hypertension, and obesity, which are known risk factors for atherosclerosis. The present study was designed to investigate the effects of oleic acid (OA), an 18-carbon cis-monosaturated fatty acid on proliferation of vascular smooth muscle cells (VSMC). Incubation of a rat VSMC (A10 cells) with OA (50 microM) resulted in an increase of cells entering the S phase of the cell cycle. In consistent with the effects on cell cycle distribution, OA stimulated VSMC proliferation in a dose-dependent manner. The mitogenic effect of OA was significantly reduced by pretreatment of LY294002 (5 microM) or wortmannin (1 microM), potent, and specific inhibitors of phosphatidylinositol 3-kinase (PI3K). OA also induced activation of Akt/protein kinase B (PKB) in a time-dependent manner. OA-induced activation of Akt/PKB was inhibited by either LY294002 or wortmannin. Taken together, these experiments show that the enhanced phosphorylation of Akt/PKB by OA is dependent on PI3K and suggest that this signaling event may be important for the regulation of OA-induced VSMC proliferation.
Yun
Mi Ran
MR
MRC for Ischemic Tissue Regeneration, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea.
Lee
Ji Young
JY
Park
Han Seong
HS
Heo
Hye Jin
HJ
Park
Ji Young
JY
Bae
Sun Sik
SS
Hong
Ki Whan
KW
Sung
Sang Min
SM
Kim
Chi Dae
CD
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D019301:Oleic Acid / Q000494:pharmacology* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D019301:Oleic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt