TY - JOUR
T1 - Limited macrophage positional dynamics in progressing or regressing murine atherosclerotic plaques-brief report
AU - Williams, Jesse W.
AU - Martel, Catherine
AU - Potteaux, Stephane
AU - Esaulova, Ekaterina
AU - Ingersoll, Molly A.
AU - Elvington, Andrew
AU - Saunders, Brian T.
AU - Huang, Li Hao
AU - Habenicht, Andreas J.
AU - Zinselmeyer, Bernd H.
AU - Randolph, Gwendalyn J.
N1 - Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - Objective-Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. Approach and Results-In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders. Thus, to test macrophage dynamics in plaques over a longer period of time in progressing and regressing disease, we quantified displacement of nondegradable phagocytic particles within macrophages for up to 6 weeks. In progressing plaques, macrophage-associated particles appeared to mobilize to deeper layers in plaque, whereas in regressing plaques, the label was persistently located near the lumen. By measuring the distance of the particles from the floor of the plaque, we discovered that particles remained at the same distance from the floor regardless of plaque progression or regression. The apparent deeper penetration of labeled cells in progressing conditions could be attributed to monocyte recruitment that generated new superficial layers of macrophages over the labeled phagocytes. Conclusions-Although there may be individual exceptions, as a population, newly differentiated macrophages fail to penetrate significantly deeper than the limited depth they reside on initial entry, regardless of plaque progression, or regression. These limited dynamics may prevent macrophages from escaping areas with unfavorable conditions (such as hypoxia) and pose a challenge for newly recruited macrophages to clear debris through efferocytosis deep within plaque. Visual Overview-An online visual overview is available for this article.
AB - Objective-Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. Approach and Results-In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders. Thus, to test macrophage dynamics in plaques over a longer period of time in progressing and regressing disease, we quantified displacement of nondegradable phagocytic particles within macrophages for up to 6 weeks. In progressing plaques, macrophage-associated particles appeared to mobilize to deeper layers in plaque, whereas in regressing plaques, the label was persistently located near the lumen. By measuring the distance of the particles from the floor of the plaque, we discovered that particles remained at the same distance from the floor regardless of plaque progression or regression. The apparent deeper penetration of labeled cells in progressing conditions could be attributed to monocyte recruitment that generated new superficial layers of macrophages over the labeled phagocytes. Conclusions-Although there may be individual exceptions, as a population, newly differentiated macrophages fail to penetrate significantly deeper than the limited depth they reside on initial entry, regardless of plaque progression, or regression. These limited dynamics may prevent macrophages from escaping areas with unfavorable conditions (such as hypoxia) and pose a challenge for newly recruited macrophages to clear debris through efferocytosis deep within plaque. Visual Overview-An online visual overview is available for this article.
KW - Arteriosclerosis
KW - Cell adhesion
KW - Inflammation
KW - Intravital microscopy
KW - Monocytes
UR - http://www.scopus.com/inward/record.url?scp=85055610767&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.118.311319
DO - 10.1161/ATVBAHA.118.311319
M3 - Article
C2 - 29903736
AN - SCOPUS:85055610767
SN - 1079-5642
VL - 38
SP - 1702
EP - 1710
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 8
ER -