title: Detection of altered extracellular matrix in surface layers of unstable carotid plaque: an optical spectroscopy, birefringence and microarray genetic analysis.
abstract: Erosion and rupture of surface layers in atherosclerotic plaque can cause heart attack and stroke; however, changes in luminal surface composition are incompletely defined. Laser-induced fluorescence spectroscopy (LIFS), with limited tissue penetration, was used to investigate the surface of unstable carotid plaque and correlated with microscopy, birefringence and gene expression. Arterial matrix collagens I, III and elastin were assessed in unstable plaques (n = 25) and reference left internal mammary arteries (LIMA, n = 10). LIFS in addition to selective histological staining with picrosirius red, Movat pentachrome and immunostaining revealed decreased elastin and increased collagen I and III (P < 0.05) in carotid plaque when compared with LIMA. Within plaque, collagen I was elevated in the internal carotid region versus the common carotid region. Polarized light microscopy detected layers of aligned collagen and associated mechanical rigidity of the fibrous cap. Microarray analysis of three carotid and three LIMA specimens confirmed up-regulation of collagen I, III and IV, lysyl oxidase and MMP-12. In conclusion, LIFS analysis coupled with microscopy revealed marked regional differences in collagen I, III and elastin in surface layers of carotid plaque; indicative of plaque instability. Birefringence measurements demonstrated mechanical rigidity and weakening of the fibrous cap with complementary changes in ECM gene expression.
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario, ON, Canada. Renee.Korol@sunnybrook.ca
authors.forename: Renee M
authors.initials: RM
authors.lastname: Korol
authors.forename: Peter B
authors.initials: PB
authors.lastname: Canham
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Kasinath
authors.initials: K
authors.lastname: Viswanathan
authors.forename: Gary G
authors.initials: GG
authors.lastname: Ferguson
authors.forename: Rob R
authors.initials: RR
authors.lastname: Hammond
authors.forename: Helen M
authors.initials: HM
authors.lastname: Finlay
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lopez
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Lucas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001718:Birefringence; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D005260:Female; D024022:Fibrillar Collagens / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D040081:Protein Array Analysis; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D024022:Fibrillar Collagens; D005456:Fluorescent Dyes; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D053508:Matrix Metalloproteinase 12