title: Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: implication for plaque progression in diabetic atherosclerosis.
abstract: Sustained inflammation may stimulate a reparative process increasing early reparative type III collagen synthesis, promoting atherosclerotic plaque progression. We evaluated inflammation, neovascularization, intra-plaque hemorrhage (IPH), and collagen deposition in human aortic atherosclerotic plaques from patients with and without diabetes mellitus (DM). Plaques were procured at autopsy from lower thoracic and abdominal aorta from DM (n = 20) and non-DM (n = 22) patients. Inflammation and neovascularization were quantified by double-label immunochemistry and the IPH grade was scored using H&E-stained sections. Type I and type III collagens were quantified using Picro-Sirius red stain with polarization microscopy and computerized planimetry. In non-DM plaques, 27%, 40%, and 33% had mild, moderate and severe inflammation in the fibrous cap and shoulder compared with 2%, 30% and 68% in DM plaques (p < 0.001). The geometric mean neovessel count was increased in DM versus non-DM plaques (140 [95% CI: 119-165] versus 59 [95% CI: 51-70]; p < 0.001). The IPH grade was increased in DM verses non-DM plaques (0.82 ± 0.11 versus 0.29 ± 0.11; p < 0.001) (percentage grade). The density of type III was increased in DM plaques (0.16 ± 0.01 versus 0.06 ± 0.01; p < 0.001) with a non-significant reduction in type I density in DM when compared with non-DM (0.28 ± 0.03 versus 0.33 ± 0.03; p = 0.303) (content per mm²). The increase in type III collagen content correlated with total neovessel content (r = 0.58; p < 0.001) in DM plaques. In conclusion, our study suggests that enhanced type III collagen deposition was associated with inflammation, neovascularization and IPH, and may be a contributing factor in DM plaque progression.
authors.affiliation: Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA. purushothaman.kothandaraman@msnyuhealth.org
authors.forename: K-Raman
authors.initials: KR
authors.lastname: Purushothaman
authors.forename: Meerarani
authors.initials: M
authors.lastname: Purushothaman
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lento
authors.forename: William N
authors.initials: WN
authors.lastname: O'Connor
authors.forename: Samin K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Moreno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D003094:Collagen