Zhan E, McIntosh VJ, Lasley RD. Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection. Am J Physiol Heart Circ Physiol 301: H1183-H1189, 2011. First published July 8, 2011; doi:10.1152/ajpheart.00264.2011.-All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A2A and/or A2B receptors modulate adenosine A1 receptor-mediated cardioprotection. Isolated perfused hearts of wildtype (WT), A2A knockout (KO), and A2BKO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A1 receptor agonist N 6 -cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 Ϯ 4% vs. 44 Ϯ 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 Ϯ 2% with CHA vs. 52 Ϯ 5% in control) in WT hearts, effects that were blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A2A receptor agonist CGS-21680 (200 nM) and the A2B agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A2A or A2B receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A2A and A2B receptors are required for adenosine A1 receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.A2a adenosine receptor; A2b adenosine receptor; knockout mice THE BENEFICIAL EFFECTS of adenosine in the ischemic-reperfused myocardium have been recognized for Ͼ25 yr. Adenosine can exert protection when given either before ischemia or at the onset of reperfusion. Substantial evidence now exists that these cardioprotective effects are achieved by the activation of extracellular adenosine receptors. All four adenosine receptor subtypes (A 1 , A 2A , A 2B , and A 3 ) are expressed in the heart, and there is evidence that all four receptors may be expressed in ventricular myocytes (4,15,26,42).There is substantial evidence that the activation of all four adenosine receptors is cardioprotective, although there do appear to be differences in the specific roles of each receptor subtype. Activation of A 1 and A 3 receptors before ischemia is cardioprotective (2,19,20,24,30,33,37,38,41), whereas A 2A and A 2B receptors appear to exert their effects during reperfusion (10,13,17,18,28,34,42,43). Adenosine A 3 receptor activation during reperfusion has been reported to be cardioprotective (8), but there are conflicting reports on ...

Hormonal replacement therapy (HRT) has recently been shown to increase the risk of cardiovascular events in women. However, it is not clear whether the adverse effect of HRT is related to dosage and/or the presence of progestin. Using a mouse model of myocardial infarction (MI), we studied the dose-effect of oestrogen replacement on mortality and cardiac remodelling and dysfunction post-MI in the absence of progestin. Six-week-old females were subjected to ovariectomy (OVX). A pellet containing a low, moderate or high dose of 17β-oestradiol (E 2 ; 0.42, 4.2 or 18.8 μg day −1 ) or placebo was implanted subcutaneously on the day of OVX. Myocardial infarction was induced 8 weeks later, and cardiac morphology and function were evaluated 8 weeks after MI. We found that E 2 at moderate and high doses adversely affected mortality. A low dose of E 2 that restored plasma oestrogen close to physiological levels had no significant effect on mortality but tended to improve cardiac function and remodelling, associated with reduced fibrosis and increased capillary density. At the moderate dose, E 2 exacerbated cardiac fibrosis, hypertrophy, dysfunction and dilatation, associated with liver and kidney enlargement and ascites. Protein kinase C and extracellular signal-regulated kinase were increased by MI but were not affected by E 2 . In summary, E 2 at a low dose tended to be cardioprotective. At increased doses that raised plasma oestrogen far beyond the physiological level, E 2 was detrimental to the heart. Our data suggest that dosage should be an important consideration when studying the effect of oestrogen replacement on the heart.

The prevalence of obesity is dramatic increased and strongly associated with cardiovascular disease. Adipokines, secreted from adipose tissues, are critical risk factors for the development of cardiomyopathy. Present study aimed to investigate the pathophysiological role of autotaxin in obesity-related cardiomyopathy. In high-fat diet-fed mice, autotaxin was mainly synthesized and secreted from adipocytes. The increased accumulation of cardiac autotaxin was positively associated with cardiac dysfunction in obese mice. Interestingly, specific blockage of adipose tissue autotaxin effectively protected against high-fat diet-induced cardiac structural disorders, left ventricular hypertrophy and dysfunction. Inhibition of autotaxin further improved high-fat diet-induced cardiac fibrosis and mitochondrial dysfunction, including improvement of mitochondrial structure, mass and activities. Our findings demonstrated intervention of adipose tissue biology could influence cardiac modification in obese mice, and adipocyte-derived autotaxin was a potential diagnostic marker and therapeutic target for obesity-related cardiomyopathy.

At present, there is no method to predict or monitor patients with AMI, and there is no specific treatment method. In order to improve the analysis of clinical influencing factors of acute myocardial infarction, based on the machine learning algorithm, this paper uses the K-means algorithm to carry out multifactor analysis and constructs a hybrid model combined with the ART2 network. Moreover, this paper simulates and analyzes the model training process and builds a system structure model based on the KNN algorithm. After constructing the model system, this paper studies the clinical influencing factors of acute myocardial infarction and combines mathematical statistics and factor analysis to carry out statistical analysis of test results. The research results show that the system model constructed in this paper has a certain effect in the clinical analysis of acute myocardial infarction.

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