Apolipoprotein C-I Induces Apoptosis in Human Aortic Smooth Muscle Cells via Recruiting Neutral Sphingomyelinase

Antonina Kolmakova, Peter Kwiterovich, Donna Virgil, Petar Alaupovic, Carolyn Knight-Gibson, Sergio F. Martin, Subroto B Chatterjee

Research output: Contribution to journalArticle

Abstract

Objectives-Apolipoprotein C-I (apoC-I) influences lipoprotein metabolism, but little is known about its cellular effects in aortic smooth muscle cells (ASMC). Methods and Results-In cultured human ASMC, apoC-I and immunoaffinity purified apoC-I-enriched high-density lipoproteins (HDL) markedly induced apoptosis (5- to 25-fold), compared with control cells, apoC-I-poor HDL, and apolipoprotein C-III (apoC-III) as determined by 4′, 6-diamidino-2-phenylindole dihydrochloride staining and DNA ladder assay. Preincubation of cells with GW4869, an inhibitor of neutral sphingomyelinase (N-SMase), blocked apoC-I-induced apoptosis, an effect that was bypassed by C-2 ceramide. The activity of N-SMase was increased 2- to 3-fold in ASMC by apoC-I, apoC-I-enriched HDL, and tumor necrosis factor α (TNF-α) (positive control) after 10 minutes and then decreased over 60 minutes, which is a kinetic pattern not seen with controls, apoC-III, and apoC-I-poor HDL, ApoC-I and apoC-I-enriched HDL stimulated the generation of ceramide, the release of cytochrome c from mitochondria, and activation of caspase-3 greater than that found in controls, apoC-III, and apoC-I-poor HDL, GW4869 inhibited apoC-I-induced production of ceramide and cytochrome c release. Conclusions-ApoC-I and apoC-I-enriched HDL activate the N-SMase-ceramide signaling pathway, leading to apoptosis in human ASMC, which is an effect that may promote plaque rupture in vivo.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 2004

    Fingerprint

Keywords

  • Apolipoprotein C-I
  • Apoptosis
  • High-density lipoproteins
  • Sphingomyelinase
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this