title: Adenosine receptor expression in an experimental animal model of myocardial infarction with preserved left ventricular ejection fraction.
abstract: Adenosine, a purine nucleoside and a "retaliatory metabolite" in ischemia, is ubiquitous in the body and increases 100-fold during ischemia. Its biological actions are mediated by four adenosine receptors (ARs): A(1), A(2A), A(2B) and A(3). The aim of this study was to determine possible myocardial alterations in AR expression in an experimental animal model of myocardial infarction (MI) with a preserved left ventricular (LV) ejection fraction. LV tissue was collected from sexually mature male farm pigs with MI (n = 6) induced by permanent surgical ligation of the left anterior descending coronary artery and from five healthy pigs (C). mRNA expression of A(1)R, A(2A)R, A(2B)R, A(3)R and TNF-α was determined by real-time PCR in tissue collected from border (BZ) and remote zones (RZ) of the infarcted area and from LV of C. BZ, RZ and samples of C were stained immunohistochemically to investigate A(3)R immunoreaction. After 4 weeks a different regulation of ARs was observed. A(1)R mRNA expression was significantly lower in the infarct regions than in controls (C = 0.75 ± 0.2, BZ = 0.05 ± 0.2, RZ = 0.07 ± 0.02 p = 0.0025, p = 0.0016, C vs. BZ and RZ, respectively). Conversely A(3)R was higher in infarct areas (C = 0.94 ± 0.2, BZ = 2.85 ± 0.5, RZ = 3.48 ± 1.0, p = 0.048 C vs. RZ). No significant differences were observed for A(2A)R (C = 1.58 ± 0.6, BZ = 0.42 ± 0.1, RZ = 1.37 ± 0.6) and A(2B)R (C = 1.66 ± 0.2, BZ = 1.54 ± 0.5, RZ = 1.25 ± 0.4). A(3)R expression was confirmed by immunohistochemical analysis and was principally localized in cardiomyocytes. TNF-α mRNA results were: C 0.41 ± 0.25; BZ 1.60 ± 0.19; RZ 0.17 ± 0.04. The balance between A(1)R and A(3)R as well as between A(2A)R and A(2B)R was consistent with adaptative retaliatory anti-ischemic adenosinergic changes in the infarcted heart with preserved LV function.
authors.affiliation: Laboratory of Cardiovascular Biochemistry, CNR Institute of Clinical Physiology, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cabiati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martino
authors.forename: Letizia
authors.initials: L
authors.lastname: Mattii
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Prescimone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Maria-Aurora
authors.initials: MA
authors.lastname: Morales
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Ry
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D000241:Adenosine