Cellular and molecular changes associated with inhibitory effect of pioglitazone on neointimal growth in patients with type 2 diabetes after zotarolimus-eluting stent implantation

Soon Jun Hong, Sung Tae Kim, Tae Jin Kim, Eun Ok Kim, Chul Min Ahn, Jae Hyoung Park, Je Sang Kim, Kyung-Mi Lee, Do-Sun Lim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective- To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation. Methods and Results- Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action. Conclusion- Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.

Original languageEnglish
Pages (from-to)2655-2665
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number12
DOIs
Publication statusPublished - 2010 Dec 1

Fingerprint

pioglitazone
Type 2 Diabetes Mellitus
Stents
Growth
Anti-Inflammatory Agents
Interventional Ultrasonography
zotarolimus
Chemokine CCL2
Chemokine Receptors
Vascular Smooth Muscle
Natural Killer Cells
Interleukin-10

Keywords

  • diabetes
  • inflammation
  • pioglitazone
  • restenosis
  • zotarolimus-eluting stent

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cellular and molecular changes associated with inhibitory effect of pioglitazone on neointimal growth in patients with type 2 diabetes after zotarolimus-eluting stent implantation. / Hong, Soon Jun; Kim, Sung Tae; Kim, Tae Jin; Kim, Eun Ok; Ahn, Chul Min; Park, Jae Hyoung; Kim, Je Sang; Lee, Kyung-Mi; Lim, Do-Sun.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 12, 01.12.2010, p. 2655-2665.

Research output: Contribution to journalArticle

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abstract = "Objective- To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation. Methods and Results- Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action. Conclusion- Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.",
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AU - Lee, Kyung-Mi

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