ABSTRACT
BACKGROUND: Altered 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. METHODS: Artery 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 monoclonal antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50). RESULTS: A2AR expression on PBMCs was lower in patients than controls (median1.3 [range 0.6-1.8] vs 1.75 [1.45-2.1] arbitrary units; Pâ¯<â¯0.01), and correlated with A2AR expression in artery tissues (Pearson's râ¯=â¯0.71; Pâ¯<â¯0.01). Basal and maximally stimulated cAMP production of PBMCs was lower in patients vs controls: 172 [90-310] vs 244 [110-380] pg/106 cells (Pâ¯<â¯0.05) and 375 [160-659] vs 670 [410-980] pg/106 cells (Pâ¯<â¯0.05), respectively. A high KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. CONCLUSION: A2AR 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.
Subject(s)
Adenosine/pharmacology , Coronary Artery Disease/etiology , Lower Extremity/blood supply , Peripheral Arterial Disease/drug therapy , Receptor, Adenosine A2A/metabolism , Aged , Biomarkers/metabolism , Coronary Artery Disease/drug therapy , Coronary Artery Disease/metabolism , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/metabolism , Pilot Projects , Prognosis , Vasodilator Agents/pharmacologyABSTRACT
BACKGROUND: Mycobacterium malmoense infections have frequently been reported in northern Europe since the late 1970s. Factors accounting for this geographically localized epidemiology remain poorly understood. CASE PRESENTATION: We report the case of a 54-year old man concomitantly diagnosed with non-small cell lung carcinoma and M. malmoense pulmonary infection. We present detailed clinical, microbiological and radiological elements strongly arguing for M. malmoense true pathogenicity. Since M. malmoense infection has rarely been reported in France, we also provide elements of the epidemiological investigation and a literature review of potential acquisition and transmission pathways of M. malmoense. We detail therapeutic interventions and subsequent favorable evolution. CONCLUSION: Mycobacterium malmoense is a recognized respiratory pathogen for which routes of infection need to be better investigated.