Modulation of cardiac remodeling by adenosine: In vitro and in vivo effects

Villarreal, Francisco; Zimmermann, Scott; Makhsudova, Lala; Montag, Annika C.; Erion, Mark D.; Bullough, David A.; Ito, Bruce R.

doi:10.1007/978-1-4419-9238-3_3

Cited by 13 publications

(17 citation statements)

References 58 publications

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“…[31][32][33] In the present study, we demonstrated that the long-term administration of either DIP or CADO that starts 1 week after the onset of MI, during which time the necrotic process may be completed, 34 improves cardiac performance in MI rats, as indicated by hemodynamic and echocardiographic parameters. To the best of our knowledge, this study is the first to document that adenosine administered after the completion of the necrotic process exerts cardioprotective effects.…”

Section: Discussionsupporting

confidence: 60%

Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats

et al. 2006

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Background-Adenosine inhibits proliferation of cardiac fibroblasts and hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac remodeling. In the present study, we investigated whether chronic stimulation of adenosine receptors begun after myocardial infarction (MI) prevents cardiac remodeling. Methods and Results-MI was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. One week after the onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP; the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after treatment, hemodynamic and echocardiographic parameters in the DIP and CADO groups were significantly improved compared with the vehicle group. These hemodynamic and echocardiographic improvements were blunted by either 8-SPT or the selective adenosine A2b antagonist MRS1754 but not by the selective antagonists for other subtypes of adenosine receptors. The collagen volume fraction was smaller, and gene expression of the molecules associated with cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was reduced in the DIP and CADO groups compared with the vehicle group, both of which were attenuated by either 8-SPT or MRS1754. Conclusions-Long-term

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Section: Discussionsupporting

confidence: 60%

Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats

et al. 2006

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“…A1 antagonists improve glomerular perfusion and promote diuresis, whereas A1 receptor stimulation provides cardiac ischemic preconditioning [106] reducing both production of endothelin [107] and activation of the renin-angiotensin system [108]. Renal benefits of A1 antagonists were recently reported in human HF, while in experimental models, enhancing adenosine by extrinsic or intrinsic means attenuates cardiac hypertrophy and improves cardiac function [109] and also decreases infarct expansion and extracellular fibrosis in [110]. Given the directionally opposite effects on kidney and heart, it remains to be seen how this may evolve as a method to reverse chronic HF remodeling.…”

Section: Novel Therapies For Reverse Remodelingmentioning

confidence: 97%

Reversing chronic remodeling in heart failure

Mudd¹,

Kass²

2007

Expert Review of Cardiovascular Therapy

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Chronic heart failure is a debilitating condition with significant morbidity, mortality and an increasing economic burden. The past 20 years have witnessed great strides in both medical and device-based therapies for heart failure. Central to these developments has been the ability to favorably reverse the chronic processes by which the failing heart remodels. In addition to pharmacotherapies, such as beta-blockade, and inhibition of the renin-angiotensin-aldosterone system, surgical remodeling, containment devices and new methods to restore synchronous contraction have been added to the armamentarium, in some instances, providing clear improvement to both symptoms and mortality. In more advanced stages of heart failure, left ventricular-assist devices provide marked unloading of the failing ventricle and such therapy has provided unique insights into the molecular and cellular mechanisms underlying reverse remodeling, given the immediate access to cardiac tissue. Genetic and cellular approaches, as well as new small molecule targets, may provide future avenues for reverse remodeling of the failing heart, improving symptoms and disease outcome.

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“…The ability of the nucleoside adenosine (ADO) to inhibit CF proliferation, protein, and/or collagen synthesis (7,11,12,37) may ameliorate myocardial fibrosis and chamber remodeling. Although the modulation of these effects by ADO appears to occur predominantly via A 2 receptors (7,11,13), the results have not been carefully validated and the participant signaling pathways in CF have not been unequivocally established.…”

mentioning

confidence: 99%

Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

Epperson

Brunton

Ramírez-Sánchez

et al. 2009

American Journal of Physiology-Cell Physiology

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The ability of adenosine (ADO) to inhibit proliferation and protein synthesis (in particular, collagen synthesis) in cardiac fibroblasts (CF) may ameliorate adverse cardiac remodeling and fibrosis seen in heart failure patients. However, little is known about the signaling pathways that ADO may modulate in CF to alter cell phenotype. Accordingly, this study was designed to identify ADO receptors (AR) and the signaling pathways linked to them in primary cultures of adult rat CF. Quantitative RT-PCR data indicate that the mRNAs for all four known ARs (A(1)R, A(2a)R, A(2b)R, and A(3)R) are present in rat CF, with a greater prevalence of A(2) receptor subtypes. No coupling of AR to the G(q)-phospholipase C signaling pathway or to mobilization of calcium is measurable. Studies using subtype specific agents imply that the A(2a)R and A(2b)R couple to G(s)-adenylyl cyclase and A(1)R couple weakly to G(i)-adenylyl cyclase. 2-Chloroadenosine, 5'-N-ethylcarboxamidoadensoine, and other agents that elevate cellular cAMP stimulate extracellular signal-regulated kinase 1/2 activity in a pertussis toxin-insensitive manner. We conclude that a combination of cAMP-dependent signals generated via A(2a) and A(2b) receptors likely mediate ADO signaling in adult rat CF.

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Modulation of cardiac remodeling by adenosine: In vitro and in vivo effects

Cited by 13 publications

References 58 publications

Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats

Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats

Reversing chronic remodeling in heart failure

Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

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