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): A1, A2A, A2B and A3. 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 A1R, A2AR, A2BR, A3R 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 A3R immunoreaction. After 4 weeks a different regulation of ARs was observed. A1R 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 A3R 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 A2AR (C = 1.58 ± 0.6, BZ = 0.42 ± 0.1, RZ = 1.37 ± 0.6) and A2BR (C = 1.66 ± 0.2, BZ = 1.54 ± 0.5, RZ = 1.25 ± 0.4). A3R 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 A1R and A3R as well as between A2AR and A2BR was consistent with adaptative retaliatory anti-ischemic adenosinergic changes in the infarcted heart with preserved LV function.
Adenosine receptor expression in an experimental animal model of myocardial infarction with preserved left ventricular ejection fraction
CABIATI, MANUELA;MATTII, LETIZIA;
2014-01-01
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): A1, A2A, A2B and A3. 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 A1R, A2AR, A2BR, A3R 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 A3R immunoreaction. After 4 weeks a different regulation of ARs was observed. A1R 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 A3R 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 A2AR (C = 1.58 ± 0.6, BZ = 0.42 ± 0.1, RZ = 1.37 ± 0.6) and A2BR (C = 1.66 ± 0.2, BZ = 1.54 ± 0.5, RZ = 1.25 ± 0.4). A3R 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 A1R and A3R as well as between A2AR and A2BR was consistent with adaptative retaliatory anti-ischemic adenosinergic changes in the infarcted heart with preserved LV function.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
