Regular Article
Dexamethasone Suppresses Vascular Smooth Muscle Cell Proliferation

https://doi.org/10.1006/jsre.1999.5665Get rights and content

Abstract

Background. Experimental studies in vivo have demonstrated that dexamethasone inhibits neointimal hyperplasia following arterial injury. The mechanisms of this inhibition have not been clearly defined. Our objective was to test the hypothesis that dexamethasone directly suppresses smooth muscle cell (SMC) proliferation by inhibiting cell cycle progression and the expression of key cell cycle-dependent genes.

Methods. Cultured rat aortic SMC were treated with incremental concentrations of dexamethasone and cell number was determined after 72 h. To determine if dexamethasone inhibited cell cycle progression, cells were synchronized, then restimulated to enter the cell cycle, and treated with or without dexamethasone. DNA synthesis was determined 24 h after restimulation by measuring [3H]thymidine incorporation. To define the point of action of dexamethasone in the cell cycle, synchronized SMC were treated with dexamethasone (10−7 M) at various time points after entry into the cell cycle. Flow cytometry and Northern blots were performed to examine cell cycle progression and the expression of smooth muscle cell cycle-dependent genes c-fos, c-myc, and thymidine kinase (TK).

Results. Dexamethasone treatment induced a concentration-dependent inhibition of SMC proliferation and DNA synthesis. The cell cycle progression of synchronized SMC from G1 into S phase was inhibited by dexamethasone, even when added as late as 16 h after restimulation. The expression of TK was suppressed by dexamethasone, while c-fos and c-myc were not affected.

Conclusions. Dexamethasone inhibits the proliferation of SMC in a concentration-dependent fashion. This inhibition is associated with a block in cell cycle progression late in G1 phase of the cell cycle. Consistent with this finding, dexamethasone does not alter the expression of the early cell cycle-dependent genes c-fos and c-myc, but significantly inhibits the expression of TK, a marker of late G1 phase.

References (31)

  • M.W. Liu et al.

    Restenosis after coronary angioplasty

    Circulation

    (1989)
  • A.W. Clowes et al.

    Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium

    Lab. Invest.

    (1983)
  • A.W. Clowes et al.

    Mechanisms of stenosis after arterial injury

    Lab. Invest.

    (1983)
  • S.M. Schwartz et al.

    Replication of smooth muscle cells in vascular disease

    Circ. Res.

    (1986)
  • K. Rhee et al.

    c-Myc and cyclin D3 CcnD3 genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation

    Cancer Res.

    (1995)
  • Cited by (36)

    • Evaluation of drug-eluting nanoparticle coating on magnesium alloy for development of next generation bioabsorbable cardiovascular stents

      2022, Medical Engineering and Physics
      Citation Excerpt :

      In addition, we demonstrated that increased Mg ion concentration is the main reason of decreased cell viability [68]. Although the effect of dexamethasone on SMCs has been shown by some studies [69,70], constant cell viability of Dexa group after 72 h has been observed in our study. It might indicate that Dexa in solution form had no effect on SMCs or this concentration was less to be effective.

    • Biodegradable nanoparticles for drug and gene delivery to cells and tissue

      2012, Advanced Drug Delivery Reviews
      Citation Excerpt :

      As shown above for cultured cells, nanoparticles may enter into the intracellular space by endocytosis, thus providing localized drug effects at a cellular level. This is important for certain drugs like dexamethasone because the receptors for this drug are intracellular [135]. Intracellular delivery is also important for gene therapy approaches to achieve greater level of gene expression.

    • The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1α expression

      2011, Experimental Cell Research
      Citation Excerpt :

      Vascular smooth muscle cell (VSMC) migration is the critical event in the progression of neointimal thicking and restenosis [4]. Dexamethasone has been shown to suppress VSMC migration and proliferation [5,6]. Several animal studies demonstrated that dexamethasone exhibited beneficial effects on cholesterol-induced atherosclerosis and neointimal formation in arterial injury [7–10].

    • Design Principles in Biomaterials and Scaffolds

      2011, Principles of Regenerative Medicine
    • Design Principles in Biomaterials and Scaffolds

      2010, Principles of Regenerative Medicine, Second Edition
    • Design Principles in Biomaterials and Scaffolds

      2008, Principles of Regenerative Medicine
    View all citing articles on Scopus

    Presented at the Annual Meeting of the Association for Academic Surgery, Seattle, Washington, November 18–22, 1998.

    1

    To whom correspondence and reprint requests should be addressed at UCLA Center for Health Sciences, Department of Surgery, 10833 LeConte Ave., Los Angeles, CA 90095.

    View full text