Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells

Sung Kwon Moon, Larry J. Thompson, Nageswara Madamanchi, Scott Ballinger, John Papaconstantinou, Chris Horaist, Marschall S. Runge, Cam Patterson

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106 Scopus citations

Abstract

The cellular mechanisms that contribute to the acceleration of atherosclerosis in aging populations are poorly understood, although it is hypothesized that changes in the proliferative capacity of vascular smooth muscle cells is contributory. We addressed the relationship among aging, generation of reactive oxygen species (ROS), and proliferation in primary culture smooth muscle cells (SMC) derived from the aortas of young (4 mo old) and aged (16 mo old) mice to understand the phenotypic modulation of these cells as aging occurs. SMC from aged mice had decreased proliferative capacity in response to α-thrombin stimulation, yet generated higher levels of ROS and had constitutively increased mitogen-activated protein kinase activity, in comparison with cells from younger mice. These effects may be explained by dysregulation of cell cycle-associated proteins such as cyclin D1 and p27Kip1 in SMC from aged mice. Increased ROS generation was associated with decreased endogenous antioxidant activity, increased lipid peroxidation, and mitochondrial DNA damage. Accrual of oxidant-induced damage and decreased proliferative capacity in SMC may explain, in part, the age-associated transition to plaque instability in humans with atherosclerosis.

Original languageEnglish (US)
Pages (from-to)H2779-H2788
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number6 49-6
StatePublished - Jul 3 2001

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Keywords

  • Atherosclerosis
  • Cell cycle
  • DNA damage
  • Lipid peroxidation
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Moon, S. K., Thompson, L. J., Madamanchi, N., Ballinger, S., Papaconstantinou, J., Horaist, C., Runge, M. S., & Patterson, C. (2001). Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells. American Journal of Physiology - Heart and Circulatory Physiology, 280(6 49-6), H2779-H2788.