Resident intimal dendritic cells and the initiation of atherosclerosis.
OBJECTIVE
To highlight the fact that regional differences in the normal arterial intima are critical to atherosclerotic lesion formation driven by systemic risk factors.


RESULTS
At arterial curvatures, bifurcations and branches unique hemodynamics influence endothelial cell signaling and gene expression patterns, which create a proinflammatory environment, with low-grade recruitment of monocytes and accumulation of cells with dendritic features in the intima. Upon induction of hypercholesterolemia, these resident intimal dendritic cells initiate atherosclerosis by rapidly engulfing lipid and becoming the first foam cells in nascent lesions. This step precedes endothelial cell activation and increased monocyte recruitment.


CONCLUSIONS
The unique features of the arterial intima at atherosclerosis-susceptible sites do not lead to disease under normal physiological conditions, but this intimal environment promotes the initiation of atherogenesis upon induction of systemic risk factors such as hypercholesterolemia.
Cybulsky
Myron I
MI
Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. myron.cybulsky@utoronto.ca
Jongstra-Bilen
Jenny
J
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000276:immunology / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D018056:Hemorheology; D006801:Humans; D017539:Tunica Intima / Q000166:cytology / Q000276:immunology* / Q000473:pathology*