Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration

Eddie L. Greene, Gang Lu, Da Zhang, Brent M. Egan

Research output: Contribution to journalArticle

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Abstract

Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants Creactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 μmol/L increases VSMC migration 60± 10% over control (P<0.001). Ang II (10 -9 mol/L) increases VSMC migration by 62±13% and 73% over control, respectively (P<0.01). Coincubation of cells with OA and Ang II' produces a nearly additive increase in VSMC cell migration at 107±20% (P<0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation, VSMC migration in response to OA alone and with Ang II was also inhibited by N-acetyl-cysteine. MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.

Original languageEnglish (US)
Pages (from-to)308-312
Number of pages5
JournalHypertension
Volume37
Issue number2 I
StatePublished - 2001

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Keywords

  • Angiotensin II
  • Muscle
  • Oxidative stress
  • Protein kinases
  • Signal transduction
  • Smooth
  • Vascular

ASJC Scopus subject areas

  • Internal Medicine

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