Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo: Implications in the treatment of restenosis after angioplasty

Jai Pal Singh, Kimberly J. Rothfuss, Todd R. Wiernicki, William B. Lacefield, L. Kurtz, Raymond F. Brown, Kellie A. Brune, Dianna Bailey, Gregory P. Dubé

Research output: Contribution to journalArticle

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Abstract

Objectives. The effect of dipyridimole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. Background. In addition to antiplatetet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. Methods. Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. Results. Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 μg/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatetet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenutated by increasing the serum concentration in the culture medium.Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyrldamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. Conclusions. Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.

Original languageEnglish (US)
Pages (from-to)665-671
Number of pages7
JournalJournal of the American College of Cardiology
Volume23
Issue number3
DOIs
StatePublished - Mar 1 1994
Externally publishedYes

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Dipyridamole
Vascular Smooth Muscle
Angioplasty
Smooth Muscle Myocytes
Cell Proliferation
Tunica Intima
Therapeutics
Wounds and Injuries
In Vitro Techniques
Arteries
Serum
Vascular System Injuries
Femoral Artery
Carotid Arteries
Culture Media
Blood Proteins
Rabbits

ASJC Scopus subject areas

  • Nursing(all)

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Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo : Implications in the treatment of restenosis after angioplasty. / Singh, Jai Pal; Rothfuss, Kimberly J.; Wiernicki, Todd R.; Lacefield, William B.; Kurtz, L.; Brown, Raymond F.; Brune, Kellie A.; Bailey, Dianna; Dubé, Gregory P.

In: Journal of the American College of Cardiology, Vol. 23, No. 3, 01.03.1994, p. 665-671.

Research output: Contribution to journalArticle

Singh, Jai Pal ; Rothfuss, Kimberly J. ; Wiernicki, Todd R. ; Lacefield, William B. ; Kurtz, L. ; Brown, Raymond F. ; Brune, Kellie A. ; Bailey, Dianna ; Dubé, Gregory P. / Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo : Implications in the treatment of restenosis after angioplasty. In: Journal of the American College of Cardiology. 1994 ; Vol. 23, No. 3. pp. 665-671.
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abstract = "Objectives. The effect of dipyridimole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. Background. In addition to antiplatetet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. Methods. Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. Results. Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50{\%} inhibition at 7 μg/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatetet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenutated by increasing the serum concentration in the culture medium.Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63{\%} inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyrldamole also inhibited intimal thickening (20{\%}, p < 0.05) after balloon injury. Conclusions. Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.",
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T1 - Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo

T2 - Implications in the treatment of restenosis after angioplasty

AU - Singh, Jai Pal

AU - Rothfuss, Kimberly J.

AU - Wiernicki, Todd R.

AU - Lacefield, William B.

AU - Kurtz, L.

AU - Brown, Raymond F.

AU - Brune, Kellie A.

AU - Bailey, Dianna

AU - Dubé, Gregory P.

PY - 1994/3/1

Y1 - 1994/3/1

N2 - Objectives. The effect of dipyridimole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. Background. In addition to antiplatetet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. Methods. Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. Results. Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 μg/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatetet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenutated by increasing the serum concentration in the culture medium.Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyrldamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. Conclusions. Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.

AB - Objectives. The effect of dipyridimole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. Background. In addition to antiplatetet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. Methods. Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. Results. Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 μg/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatetet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenutated by increasing the serum concentration in the culture medium.Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyrldamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. Conclusions. Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.

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