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Upregulation of Adenosine A1 Receptor in Coronary Atherosclerosis in the Metabolic Syndrome and in the in Vitro Organ Culture Model of Coronary Atherosclerosis
Author(s) -
Long Xin,
Edwards Jason M,
Neeb Zachary,
Alloosh Mouhamad,
Sturek Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.924.1
Subject(s) - downregulation and upregulation , organ culture , coronary atherosclerosis , medicine , in vitro , adenosine , receptor , endocrinology , artery , mapk/erk pathway , phosphorylation , biology , coronary artery disease , biochemistry , gene
Ossabaw miniature swine fed excess atherogenic diet develop metabolic syndrome (MetS) and coronary atherosclerosis similar to humans. Organ culture is a useful in vitro model of arterial injury/atherosclerosis. Our lab previously made the novel discovery that adenosine A1 receptor (A1R) signaling via ERK phosphorylation mediates smooth muscle cell proliferation in intact coronary rings from Ossabaw pigs. Thus, we hypothesized that A1R will be upregulated in atherosclerotic coronary artery of MetS Ossabaw pigs and also in the organ culture model. Coronary intimal thickness in MetS pigs (n=7) increased 2.4‐fold compared to control pigs (n=6) (p<0.05). A1R mRNA and protein increased 4‐fold and 3‐fold, respectively, in MetS compared to control pigs (p<0.05). A1R mRNA increased 5‐fold in the 2‐day organ cultured coronary compared to cold stored ones (p<0.05), and A1R protein increased 2‐fold in the 4‐day organ cultured coronary compared to cold stored. In an in vitro organ culture model of arterial injury, A1R stimulated ERK phosphorylation increased 8‐fold compared to non‐injured artery segments. CONCLUSION: Upregulation of A1 receptor expression and ERK signaling may contribute to coronary atherosclerosis in MetS and in the in vitro organ culture model of arterial injury.