Published online before print July 21, 2003, doi: 10.1161/01.CIR.0000080883.53863.5C
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(Circulation. 2003;108:508.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Cloning of a Novel Prolyl 4-Hydroxylase Subunit Expressed in the Fibrous Cap of Human Atherosclerotic Plaque
From the Robarts Research Institute (Vascular Biology Group), London Health Sciences Centre, Departments of Medicine (Cardiology), Biochemistry, Medical Biophysics, University of Western Ontario, London, Canada.
Correspondence to J. Geoffrey Pickering MD, PhD, London Health Sciences Centre, 339 Windermere Rd, London, Ontario N6A 5A5, Canada. E-mail gpickering{at}robarts.ca
Received July 29, 2002; de novo received March 7, 2003; revision received April 29, 2003; accepted May 2, 2003.
Background— The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase.
Methods and Results— We report the cloning of a novel prolyl 4-hydroxylase catalytic (
) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe2+ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity. Furthermore, when the recombinant protein was expressed in cells, it associated with the ß-subunit of prolyl 4-hydroxylase and could catalyze prolyl 4-hydroxylation of a collagen-like peptide. The tissue distribution was dissimilar from that of the 2 previously cloned -subunits, suggesting a role beyond redundancy. Importantly, the novel gene was expressed in the fibrous cap of human carotid atherosclerotic lesions.
Conclusions— The discovery of a novel prolyl 4-hydroxylase -subunit, here termed the (III)-subunit, suggests a new participant in collagen synthesis that, in view of the expression findings, may be relevant to atherosclerotic disease.
Key Words: atherosclerosis • muscle, smooth • collagen • genes
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