Human HDL containing a novel apoC-I isoform induces smooth muscle cell apoptosis.
OBJECTIVE
We discovered that some adults with coronary heart disease (CHD) have a high density lipoprotein (HDL) subclass which induces human aortic smooth muscle cell (ASMC) apoptosis in vitro. The purpose of this investigation was to determine what properties differentiate apoptotic and non-apoptotic HDL subclasses in adults with and without CHD.


RESULTS
Density gradient ultracentrifugation was used to measure the particle density distribution and to isolate two HDL subclass fractions, HDL2 and HDL3, from 21 individuals, including 12 without CHD. The HDL fractions were incubated with ASMCs for 24 h; apoptosis was quantitated relative to C2-ceramide and tumour necrosis factor-alpha (TNF-α). The observed effect of some HDL subclasses on apoptosis was ∼6-fold greater than TNF-α and ∼16-fold greater than the cell medium. We observed that apoptotic HDL was (i) predominately associated with the HDL2 subclass; (ii) almost exclusively found in individuals with a higher apoC-I serum level and a novel, higher molecular weight isoform of apoC-I; and (iii) more common in adults with CHD, the majority of whom had high (>60 mg/dL) HDL-C levels.


CONCLUSIONS
Some HDL subclasses enriched in a novel isoform of apoC-I induce extensive ASMC apoptosis in vitro. Individuals with this apoptotic HDL phenotype generally have higher apoC-I and HDL-C levels consistent with an inhibitory effect of apoC-I on cholesteryl ester transfer protein activity. The association of this phenotype with processes that can promote plaque rupture may explain a source of CHD risk not accounted for by the classical risk factors.
Department of Internal Medicine and Department of Pediatrics, Scott & White Healthcare, Temple, TX 76508, USA. cmcneal@swmail.sw.org
Catherine J
CJ
McNeal
Subroto
S
Chatterjee
Jennifer
J
Hou
London S
LS
Worthy
Craig D
CD
Larner
Ronald D
RD
Macfarlane
Petar
P
Alaupovic
Robert W
RW
Brocia
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053302:Apolipoprotein C-I / Q000032:analysis / Q000502:physiology*; D017209:Apoptosis; D053480:Cholesterol Ester Transfer Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000032:analysis / Q000145:classification / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D053302:Apolipoprotein C-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL