Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries

Roger Charles, Lakshman Sandirasegarane, Jong Yun, Nicole Bourbon, Ronald Wilson, Raymond P. Rothstein, Steven W. Levison, Mark Kester

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Neointimal hyperplasia at the site of surgical intervention is a common and deleterious complication of surgery for cardiovascular diseases. We hypothesized that direct delivery of a cell-permeable growth-arresting lipid via the balloon tip of an embolectomy catheter would limit neointimal hyperplasia after stretch injury. We have previously demonstrated that sphingolipid-derived ceramide arrested the growth of smooth muscle cell pericytes in vitro. Here, we show that ceramide-coated balloon catheters significantly reduced neointimal hyperplasia induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide treatment decreased the number of vascular smooth muscle cells entering the cell cycle without inducing apoptosis. In situ autoradiographic studies demonstrated that inflating the balloon catheter forced cell-permeable ceramide into the intimal and medial layers of the artery. Intercalation of ceramide into vascular smooth muscle cells correlated with rapid inhibition of trauma-associated phosphorylation of extracellular signal-regulated kinase and protein kinase B. These studies demonstrate the utility of cell-permeable ceramide as a novel therapy for reducing neointimal hyperplasia after balloon angioplasty.

Original languageEnglish (US)
Pages (from-to)282-288
Number of pages7
JournalCirculation research
Volume87
Issue number4
DOIs
StatePublished - Aug 18 2000

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Carotid Artery Injuries
Ceramides
Hyperplasia
Catheters
Smooth Muscle Myocytes
Balloon Angioplasty
Vascular Smooth Muscle
Balloon Embolectomy
Tunica Intima
Pericytes
Proto-Oncogene Proteins c-akt
Sphingolipids
Extracellular Signal-Regulated MAP Kinases
Wounds and Injuries
Growth
Carotid Arteries
Cell Cycle
Cardiovascular Diseases
Arteries
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Charles, Roger ; Sandirasegarane, Lakshman ; Yun, Jong ; Bourbon, Nicole ; Wilson, Ronald ; Rothstein, Raymond P. ; Levison, Steven W. ; Kester, Mark. / Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries. In: Circulation research. 2000 ; Vol. 87, No. 4. pp. 282-288.
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Charles, R, Sandirasegarane, L, Yun, J, Bourbon, N, Wilson, R, Rothstein, RP, Levison, SW & Kester, M 2000, 'Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries', Circulation research, vol. 87, no. 4, pp. 282-288. https://doi.org/10.1161/01.RES.87.4.282

Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries. / Charles, Roger; Sandirasegarane, Lakshman; Yun, Jong; Bourbon, Nicole; Wilson, Ronald; Rothstein, Raymond P.; Levison, Steven W.; Kester, Mark.

In: Circulation research, Vol. 87, No. 4, 18.08.2000, p. 282-288.

Research output: Contribution to journalArticle

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AU - Sandirasegarane, Lakshman

AU - Yun, Jong

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AU - Wilson, Ronald

AU - Rothstein, Raymond P.

AU - Levison, Steven W.

AU - Kester, Mark

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AB - Neointimal hyperplasia at the site of surgical intervention is a common and deleterious complication of surgery for cardiovascular diseases. We hypothesized that direct delivery of a cell-permeable growth-arresting lipid via the balloon tip of an embolectomy catheter would limit neointimal hyperplasia after stretch injury. We have previously demonstrated that sphingolipid-derived ceramide arrested the growth of smooth muscle cell pericytes in vitro. Here, we show that ceramide-coated balloon catheters significantly reduced neointimal hyperplasia induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide treatment decreased the number of vascular smooth muscle cells entering the cell cycle without inducing apoptosis. In situ autoradiographic studies demonstrated that inflating the balloon catheter forced cell-permeable ceramide into the intimal and medial layers of the artery. Intercalation of ceramide into vascular smooth muscle cells correlated with rapid inhibition of trauma-associated phosphorylation of extracellular signal-regulated kinase and protein kinase B. These studies demonstrate the utility of cell-permeable ceramide as a novel therapy for reducing neointimal hyperplasia after balloon angioplasty.

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