title: Type V collagen regulates the assembly of collagen fibrils in cultures of bovine vascular smooth muscle cells.
abstract: Vascular smooth muscle cells (SMCs), the major cellular constituent of the medial layer of an artery, synthesize the majority of connective tissue proteins, including fibrillar collagen types I, III, and V/XI. Proper collagen synthesis and deposition, which are important for the integrity of the arterial wall, require the antioxidant vitamin C. Vitamin C serves as cofactor for the enzymes prolyl and lysyl hydroxylase, which are responsible for the proper hydroxylation of collagen. Here, the role of type V collagen in the assembly of collagen fibrils in the extracellular matrix (ECM) of cultured vascular SMCs was investigated. Treatment of SMCs with vitamin C resulted in a dramatic induction in the levels of the cell-layer associated pepsin-resistant type V collagen, whereas only a minor induction in the levels of types I and III collagen was detected. Of note, the deposition of type V collagen was accompanied by the formation of striated collagen fibrils in the ECM. Immunohistochemistry demonstrated that type V collagen, but not type I collagen, became masked as collagen fibrils matured. Furthermore, the relative ratio of type V to type I collagen decreased as the ECM matured as a function of days in culture, and this decrease was accompanied by an increase in the diameter of collagen fibrils. Together these results suggest that the masking of type V collagen is caused by its internalization on continuous deposition of type I collagen on the exterior of the fibril. Furthermore, they suggest that type V collagen acts as framework for the initial assembly of collagen molecules into heterotypic fibrils, regulating the diameter and architecture of these fibrils.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Kypreos
authors.forename: D
authors.initials: D
authors.lastname: Birk
authors.forename: V
authors.initials: V
authors.lastname: Trinkaus-Randall
authors.forename: D J
authors.initials: DJ
authors.lastname: Hartmann
authors.forename: G E
authors.initials: GE
authors.lastname: Sonenshein
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008854:Microscopy, Electron / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D003094:Collagen