Endothelial glycocalyx dimensions are reduced in growing collateral arteries and modulate leucocyte adhesion in arteriogenesis.
During collateral artery growth, monocytes adhere to the endothelium and secrete cytokines from the perivascular space promoting arteriogenesis. Recently, the endothelial glycocalyx has been shown to modulate leucocyte infiltration in atherogenic regions. The role of this endothelial surface coating in arteriogenesis, however, has not been investigated so far. We now report that local plasma levels of hyaluronic acid are specifically increased in collateral arterial blood of coronary artery disease patients and hypothesized that components of the endothelial glycocalyx are shed during arteriogenesis, resulting in decreased glycocalyx dimensions and an increased leucocyte extravasation. In a rabbit model of femoral artery ligation, electron microscopy revealed a decrease in glycocalyx dimensions in collateral arteries compared with quiescent anastomoses (67.5 +/- 47.2 nm versus 101.0 +/- 11.3 nm; P < 0.001). This decrease was correlated with a higher number of perivascular macrophages around collateral arteries. The additional glycocalyx perturbation by local hyaluronidase infusion almost completely removed the endothelial surface layer and temporarily stimulated leucocyte accumulation in the perivascular space. However, complete perturbation of the glycocalyx by hyaluronidase infusion resulted in a significant attenuation of collateral artery growth assessed by microsphere-based perfusion measurements (ml/min/100 mmHg: hyaluronidase: 27.5 +/- 3.5;


METHODS
47.1 +/- 3.83; P < 0.001) and a lower percentage of actively proliferating vascular smooth muscle cells. A decreased expression of the shear-stress regulated pro-arteriogenic genes eNOS and TGF-beta1 suggests an impaired mechanotransduction as the underlying mechanisms. For the first time, we describe the role of the endothelial glycocalyx in collateral artery growth. Although complete abrogation led to attenuated arteriogenesis, shedding of glycocalyx components is observed during collateral artery growth.
Department of Cardiology, AMC, University of Amsterdam, The Netherlands. sebastian.grundmann@uniklinik-freiburg.de
Sebastian
S
Grundmann
Stephan H
SH
Schirmer
Liesbeth H P
LH
Hekking
Jan Andries
JA
Post
Mihaela G
MG
Ionita
Daphne
D
de Groot
Niels
N
van Royen
Bernard
B
van den Berg
Hans
H
Vink
Martin
M
Moser
Christoph
C
Bode
Dominique
D
de Kleijn
Gerard
G
Pasterkamp
Jan J
JJ
Piek
Imo E
IE
Hoefer
D000368:Aged; D000818:Animals; D001158:Arteries / Q000473:pathology*; D002448:Cell Adhesion; D003251:Constriction, Pathologic / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008863:Microspheres; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011817:Rabbits
D052250:Nitric Oxide Synthase Type III