Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type

Atherosclerosis. 2014 Dec;237(2):464-70. doi: 10.1016/j.atherosclerosis.2014.10.019. Epub 2014 Oct 18.

Abstract

Objective: Cigarette smoking is a known risk factor for arteriosclerosis. In atheromatous plaques, vascular smooth muscle cells (VSMCs) display a phenotype that is different from the contractile type under normal conditions. Nicotine is the major pharmacological agent in cigarette smoke. However, any direct effect of nicotine on VSMCs remains uncertain. Because nicotine promotes VSMC migration, its phenotype may change due to nicotine.

Approach and results: We used human aorta primary smooth muscle cells (HuAoSMCs), differentiated with transforming growth factor-β, to investigate changes in the protein levels of differentiation markers and in the activity of mitogen-activated protein kinases (MAPKs) after exposure to 0.1 μM of nicotine for 48 h. After nicotine exposure, the protein levels of myosin II 10 (2.93-fold) and β-actin (1.66-fold), synthetic type markers, were increased. In contrast, the levels of the contractile type markers, myosin II 11 (0.63-fold), high-molecular-weight caldesmon (0.40-fold) and SM22 (0.66-fold), which concern differentiated VSMC, were decreased. Moreover, nicotine exposure induced enhanced activation of p38 MAPK (1.30-fold) and extracellular signal-regulated kinase (1.91-fold). These results indicated that the phenotype of HuAoSMCs had changed to a synthetic-like type because of nicotine exposure. Thus, nicotine is one factor that can alter protein expression of differentiation markers in VSMCs. Besides, the increase of intracellular Ca(2+) levels suggested that these effects of nicotine were mediated through nicotinic acetylcholine receptors.

Conclusion: Nicotine has already been reported to promote VSMC migration from the tunica media to atheromatous plaques in the vascular intima. This phenomenon may occur because nicotine directly induces VSMC transformation from contractile type to synthetic-like type via nicotinic acetylcholine receptors and G protein-coupled receptors.

Keywords: Atherosclerosis; Contractile type; Nicotine; Synthetic type; Vascular smooth muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology*
  • Aorta / drug effects
  • Calcium / metabolism
  • Calmodulin-Binding Proteins / chemistry
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • DNA / chemistry
  • Humans
  • MAP Kinase Signaling System
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Myocytes, Smooth Muscle / drug effects*
  • Nicotine / administration & dosage*
  • Nicotine / chemistry
  • Phenotype
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic / metabolism
  • Smoking / adverse effects
  • Transforming Growth Factor beta / metabolism
  • Tunica Media / pathology

Substances

  • Calmodulin-Binding Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Transforming Growth Factor beta
  • Nicotine
  • DNA
  • Calcium