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(Circulation. 2002;105:1396.)
© 2002 American Heart Association, Inc.

Vitamin C, Collagen, and Cracks in the Plaque

Peter Libby, MD; Masanori Aikawa, MD PhD

From the Leducq Center for Cardiovascular Research, Department of Medicine, Brigham and Woman’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Peter Libby, MD, Brigham and Woman’s Hospital, Eugene Braunwald Research Center, 221 Longwood Ave, Room 307, Boston, MA 02115. E-mail plibby@rics.bwh.harvard.edu

Key Words: Editorials • extracellular matrix • vitamin C • collagen • plaque stability

Most fatal acute myocardial infarctions result from a fracture of the plaque’s fibrous cap. We proposed the hypothesis some years ago that the level of collagen in the fibrous cap depends on a dynamic balance of synthesis and degradation.¹ We further showed that inflammatory cytokines can regulate both the expression of genes that direct interstitial collagen synthesis in vascular smooth muscle cells and the interstitial collagenases (matrix metalloproteinases 1, 8, and 13) required to initiate the breakdown of collagen fibrils.^2–5 Given the capital importance of collagen in protecting the plaque from rupture and hence thrombosis, the metabolism of this complex molecule merits consideration in depth.

See p 1485

The formation of mature fibrillar collagen involves many steps beyond gene transcription (Figure). The initial translation product, the procollagen peptide chain, undergoes extensive posttranslational modification: an especially noteworthy point during this period of exploration of the proteome. Collagen contains unusual amino acids, hydroxyproline and hydroxylysine, formed by a vitamin C–dependent process that entails enzymatic transfer of hydroxyl groups to selected proline and lysine residues in the nascent procollagen chains. Glycosyl transferases then add sugar moieties to the procollagen chains. The hydroxylated and glycosylated monomers then self-assemble into helical trimers as they traverse several intracellular compartments. Trimming the nonhelical tails (the telopeptides) from both ends of the procollagen molecule by proteinases yields the mature interstitial collagen triple helix secreted by smooth muscle cells in arteries. These building blocks then further self-aggregate into multimers and form interstitial collagen fibrils, linear structures as . . . [Full Text of this Article]

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