Use of a novel anti-proliferative compound coated on a biopolymer to mitigate platelet-derived growth factor-induced proliferation in human aortic smooth muscle cells: Comparison with sirolimus

Yong Dan Tang, Ambarish Pandey, Antonina Kolmakova, Xin Tong Wang, Subbu S. Venkatraman, Subroto B Chatterjee, Freddy Y C Boey

Research output: Contribution to journalArticle

Abstract

Drug eluting stents (DES) have become a common mode of treatment for stenosis in coronary arteries. However, currently, the use of sirolimus/paclitaxel-coated DES has come under scrutiny, because of their pro-thrombotic effects leading to potential adverse outcomes in the long run. We have previously documented that d-threo-1-phenyl-2-decanoylamino-3-morholino propanol (D-PDMP); an inhibitor of glucosylceramide synthase and lactosylceramide (LacCer) synthase markedly inhibited platelet-derived growth factor (PDGF)-induced cell proliferation. We have fabricated DES wherein, D-PDMP or sirolimus was coated on to a double layer of poly (lactic-co-glycolic acid) on a bare metal stent. The in vitro release of D-PDMP from biopolymer and its consequent effect on PDGF induced proliferation and apoptosis was assessed in human aortic smooth muscle cells (ASMC). D-PDMP was released from biopolymers in a dose-dependent fashion and was accompanied with a decrease in PDGF-induced cell proliferation, but not apoptosis. In contrast, sirolimus markedly increased apoptosis in these cells in addition to inhibiting proliferation. Our mechanistic studies revealed that D-PDMP, but not sirolimus decreased the cellular level of glucosyl and lactosylceramide that accompanied inhibition of PDGF-induced cell proliferation. Our short-term (14 days) in vivo studies in rabbits also attested to the safety and biocompatibility of the D-PDMP coated stents. Our data reveal the superiority of D-PDMP coated biopolymers over sirolimus coated biopolymers in mitigating ASMC proliferation. Such D-PDMP coated stents may be useful for localized delivery of drug to mitigate neo-vascular hyperplasia and other proliferative disorders.

Original languageEnglish (US)
Pages (from-to)721-732
Number of pages12
JournalGlycoconjugate Journal
Volume26
Issue number6 SPEC. ISS.
DOIs
StatePublished - Aug 2009

Fingerprint

1-Propanol
Biopolymers
Platelet-Derived Growth Factor
Sirolimus
Smooth Muscle Myocytes
Stents
Muscle
Cells
Cell proliferation
Drug-Eluting Stents
Cell Proliferation
ceramide glucosyltransferase
Apoptosis
Pharmaceutical Preparations
Coronary Stenosis
Paclitaxel
Biocompatibility
Hyperplasia
Blood Vessels
Metals

Keywords

  • Aortic smooth muscle cells
  • Biopolymer
  • Drug eluting stent
  • Lactosylceramide
  • Platelet derived growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Use of a novel anti-proliferative compound coated on a biopolymer to mitigate platelet-derived growth factor-induced proliferation in human aortic smooth muscle cells : Comparison with sirolimus. / Tang, Yong Dan; Pandey, Ambarish; Kolmakova, Antonina; Wang, Xin Tong; Venkatraman, Subbu S.; Chatterjee, Subroto B; Boey, Freddy Y C.

In: Glycoconjugate Journal, Vol. 26, No. 6 SPEC. ISS., 08.2009, p. 721-732.

Research output: Contribution to journalArticle

Tang, Yong Dan ; Pandey, Ambarish ; Kolmakova, Antonina ; Wang, Xin Tong ; Venkatraman, Subbu S. ; Chatterjee, Subroto B ; Boey, Freddy Y C. / Use of a novel anti-proliferative compound coated on a biopolymer to mitigate platelet-derived growth factor-induced proliferation in human aortic smooth muscle cells : Comparison with sirolimus. In: Glycoconjugate Journal. 2009 ; Vol. 26, No. 6 SPEC. ISS. pp. 721-732.
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AU - Pandey, Ambarish

AU - Kolmakova, Antonina

AU - Wang, Xin Tong

AU - Venkatraman, Subbu S.

AU - Chatterjee, Subroto B

AU - Boey, Freddy Y C

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