BackgroundAltered blood flow occurs in patients with low extremity peripheral artery disease (LE-PAD). LE-PAD is mostly associated with coronary artery disease (CAD). Adenosine is an endogenous nucleoside that affects both coronary and limb artery blood flow, mostly via the adenosine A2A receptor (A2AR). We evaluated A2AR expression and function in peripheral blood mononuclear cells (PBMCs) and the femoral artery tissues of patients with LE-PAD.
MethodsArtery tissues and PBMCs were sampled in 24 patients with intermittent claudication, and compared with PBMCs in 24 healthy subjects. Expression and function of A2AR was studied, using a A2AR antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50).
Results
A2AR expression onPBMCs was lower in patients than controls (median1.3 [range 0.6-1.8]vs1.75 [1.45-2.1] arbitrary units; P<0.01), and correlated with A2AR expression in artery tissues (Pearson's r=0.71; P<0.01). Basal and maximally stimulated cAMP production of PBMCs was lower in patients vs controls: 172 [90-310]vs244 [110-380]pg/10 6 cells (P<0.05) and 375 [160-659]vs670 [410-980]pg/10 6 cells (P<0.05), respectively. A high KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia.
ConclusionA2AR expression in the arteries of patients, correlated with their expression in PBMCs. A2AR expression was lower in patients than in controls. A single blood sample (for measurement of A2AR expression on PBMCs) may help to screen patients with LE-PAD, whereas the presence of spare receptors may help with risk stratification before vascular surgery in CAD patients with high risk of myocardial ischemia.
Background: In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles.Methods: Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K + ) concentration was also measured at rest and at the end of exercise to explore K + outflow.Results: Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K + outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels.
Conclusions:Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS.
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