Abstract 4831: The A2B Adenosine Receptor Contributes to Post-Infarction Heart Failure
Recent studies have been directed at understanding the role of the A2B receptor in regulating cardioprotection, coronary blood flow, fibroblast function, and inflammation. Unlike the other adenosine receptor subtypes, the A2B receptor is emerging as a promoter of inflammation in chronic diseases such as asthma and conditions associated with tissue fibrosis. In this study, we used A2B receptor gene “knock-out” (A2B−/−) mice to test the role of the A2B receptor in infarction-induced heart failure and cardiac remodeling. A2B−/− mice or wild-type (WT) littermates were subjected to permanent ligation of the left coronary artery or sham surgery. Cardiac morphology and function were assessed at 4 and 8 weeks after surgery by echocardiography. At the end of the study, systemic arterial and left ventricular pressures were obtained, after which the hearts were removed and histologically assessed for infarct size and fibrosis. WT hearts experienced significant left ventricular dilation and reduced systolic (fractional area shortening, myocardial performance index, and +dP/dtmax) and diastolic (end-diastolic pressure [EDP] elevated from 3.2 ± 0.8 mmHg in sham mice to 8.8 ± 1.5 mmHg in infarcted mice and tau was prolonged from 11.6 ± 1.7 ms to 22.3 ± 2.0 ms) function at 8 weeks after coronary artery ligation. Compared to WT mice, there were no significant differences in measures of post-infarction systolic function in A2B−/− mice. However, EDP and tau were significantly improved (2.5 ± 1.5 mmHg and 17 ± 1.4 ms, respectively) and were not worsened compared to sham-operated A2B−/− mice (2.7 ± 2.1 mmHg and 14.5 ± 1.8 ms, respectively). Moreover, interstitial fibrosis was elevated in the non-infarcted myocardium of WT mice subjected to coronary ligation, but not in A2B−/− mice. Importantly, infarct size (WT = 39 ± 2% of the left ventricle; A2B−/− = 43 ± 3%) and systemic blood pressure were not significantly different between WT and A2B−/− mice. The data suggest that absence of the A2B receptor results in preservation of diastolic function and decreased development of reactive fibrosis following myocardial infarction. These findings support the concept that adenosine signaling via the A2B receptor contributes to post-infarction heart failure and adverse cardiac remodeling.
This research has received full or partial funding support from the American Heart Association, AHA National Center.