Effects of adenosine deaminase and A1 receptor deficiency in normoxic and ischaemic mouse hearts

Abstract

Deficiency of ADA does not alter sensitivities of cardiovascular A1 or A2ARs (despite markedly elevated [adenosine]), but significantly improves ischaemic tolerance. Conversely, A1AR deficiency impairs ischaemic tolerance. Effects of ADA deficiency on diastolic pressure appear solely A1AR-dependent while other ARs or processes additionally contribute to improved contractile recovery and reduced cell death.

Role of A2BAdenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

“…Adenosine deaminase (ADA)-deficient mice (Blackburn et al, 1998) were maintained on ADA enzyme therapy as described previously (Blackburn et al, 2000) until the age of 6 weeks. An increase in adenosine levels in the hearts was induced by withdrawing mice from enzyme therapy for 15 days before experiments (Willems et al, 2006). The H-2K b -tsA58 transgenic mice on a C57BL/6 genetic background (Immortomouse) were purchased from Charles River Laboratories International, Inc. (Wilmington, MA).…”

“…A considerable increase in the stromal to endothelial cell ratio ؊ Stromal and Sca-1 ؉ CD31 ؉ Endothelial Cells Induced by Adenosine In Vivo. Withdrawal from ADA enzyme replacement therapy for 2 weeks has been reported to increase adenosine levels in hearts of ADA-deficient mice (Willems et al, 2006). We used this model to evaluate in vivo the effects of adenosine on VEGF production by cardiac stromal and endothelial cells.…”

“…Concentrations of extracellular adenosine were demonstrated to increase in ischemic hearts, where it becomes a part of the pathological environment (Martin et al, 1997;Willems et al, 2006). Adenosine exerts its actions via cell surface receptors of the G protein-coupled receptor family, namely A 1 , A 2A , A 2B , and A 3 (Fredholm et al, 2001).…”

A1 adenosine receptors play an essential role in protecting the embryo against hypoxia

“…A 1 AR signaling has also been shown to protect cells from damage. Deletion of adenosine deaminase leads to elevated adenosine levels and protects the heart from ischemic/ reperfusion injury (18,19). Overexpression of A 1 AR also helps to protect the heart from ischemic/reperfusion injury and conversely the loss of A 1 AR impairs ischemic tolerance (18,19).…”

“…Deletion of adenosine deaminase leads to elevated adenosine levels and protects the heart from ischemic/ reperfusion injury (18,19). Overexpression of A 1 AR also helps to protect the heart from ischemic/reperfusion injury and conversely the loss of A 1 AR impairs ischemic tolerance (18,19). In addition, adenosine signaling through the A 2a receptor has shown to be protective under hypoxic conditions in the lung by inhibiting the immune response (8).…”