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Adenosine A1 Receptor Elicits Coronary In‐stent Stenosis in Metabolic Syndrome
Author(s) -
Long Xin,
Alloosh Mouhamad,
Kitsongsermthon Jutarat,
He Yuanzu,
Park Kinam,
Sturek Michael
Publication year - 2010
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.24.1_supplement.789.1
Subject(s) - medicine , adenosine , cardiology , stent , downregulation and upregulation , restenosis , percutaneous coronary intervention , coronary stent , vasodilation , endocrinology , pharmacology , chemistry , biochemistry , myocardial infarction , gene
Adenosine is widely thought to elicit coronary vasodilation and attenuate smooth muscle proliferation, thereby providing cardioprotection. We cloned the porcine adenosine A1 receptor (A1R) subtype and found that it paradoxically stimulated proliferation of cultured coronary smooth muscle cells by extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling pathways, thus suggesting A1R dysregulation could play a role in coronary in‐stent restenosis. We utilized the Ossabaw swine model of metabolic syndrome (MetS) to test the hypothesis that A1R up‐regulation and A1R‐ERK1/2 signaling play a role in the development of coronary in‐stent stenosis in MetS. Intracoronary stent deployment followed by different durations of recovery from stenting showed A1R upregulation occurred before maximal amount of in‐stent stenosis. Swine were fed standard chow (Lean) or excess calorie atherogenic diet for over 20 weeks, which elicited MetS characteristics. We observed reduced coronary in‐stent stenosis by TAXUS (paclitaxel‐eluting) stents in MetS. Selective A1R antagonism with DPCPX‐eluting stents decreased coronary ERK1/2 activation and decreased in‐stent stenosis comparable to TAXUS. Conclusion: A1R upregulation and A1R‐ERK1/2 activation contributes to coronary in‐stent stenosis in vivo in the setting of MetS. Support: NIH RR013223, HL062552, Purina TestDiet to MS; HL078715 to KP; AHA to XL. Grant Funding Source : NIH