A(3) adenosine receptor deficiency does not influence atherogenesis.
Atherosclerosis is a multifactorial disease, the progression of which is modulated by several factors, including inflammation and hypercholesterolemia. The A(3) adenosine receptor (A(3)AR) has been reported to affect mast cell degranulation leading to inflammation, as well as to influence cardiovascular homeostasis. Here, we show that its deletion can also impact vascular smooth muscle cell (VSMC) proliferation in vitro. Based on these observations, we hypothesized that A(3)AR deficiency would affect atheromatous lesion development in vivo. Our results indicate that the expression of the matrix enzyme lysyl oxidase (LO) is increased while the proliferation potential of VSMC is decreased in A(3)AR-null aortas. This is in accordance with the previously reported inverse correlation between LO level and proliferation. Nevertheless, we found that A(3)-deficiency does not protect vessels against atherogenesis. This was demonstrated in mouse models of high fat diet-induced atherosclerosis and guidewire-induced femoral artery injury. We conclude that the contributions of the A(3)AR to inflammation and to modulating LO levels are not significant enough to control vascular response to injury.
Jones
Matthew R
MR
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Zhao
Zhihui
Z
Sullivan
Christopher P
CP
Schreiber
Barbara M
BM
Stone
Phillip J
PJ
Toselli
Paul A
PA
Kagan
Herbert M
HM
Cohen
Richard A
RA
Ravid
Katya
K
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D004261:DNA Replication; D004549:Elastin / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
D017931:DNA Primers; D043684:Receptor, Adenosine A3; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase