Markers of inflammation collocate with increased wall stress in human coronary arterial plaque.
In this study, we hypothesized that spatial relationships exist between the local mechanical environment and inflammatory marker expression in atherosclerotic plaques, and that these relationships are plaque-progression dependent. Histologic cross-sections were collected at regular intervals along the length of diseased human coronary arteries and classified as early, intermediate, advanced, or mature based on their morphological features. For each cross-section, the spatial distribution of stress was determined using a 2D heterogeneous finite element model, and the corresponding distribution of selected inflammatory markers (macrophages, matrix metalloproteinase-1 [MMP-1], and nuclear factor-kappa B [NF-κB]) were determined immunohistochemically. We found a monotonic spatial relationship between mechanical stress and activated NF-κB that was consistent in all stages of plaque progression. We also identified progression-dependent relationships between stress and both macrophage presence and MMP-1 expression. These findings add to our understanding of the role of mechanical stress in stimulating the inflammatory response, and help explain how mechanical factors may regulate complex biological changes in remodeling.
Hallow
Karen Melissa
KM
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, MC 0405, Atlanta, GA 30332, USA.
Taylor
W Robert
WR
Rachev
Alexander
A
Vito
Raymond Peter
RP
D000328:Adult; D001158:Arteries / Q000473:pathology; D015415:Biomarkers; D003331:Coronary Vessels / Q000473:pathology*; D020342:Finite Element Analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D013314:Stress, Mechanical
D015415:Biomarkers; D016328:NF-kappa B; D020782:Matrix Metalloproteinases