Guiol Claire, El Harake Sarah, Fromonot Julien, Chefrour Mohamed, Gastaldi Marguerite, Alibouch Yassine, Doublier Maxime, Deharo Pierre, Sarlon Gabrielle, Marlinge Marion, Lalevee Nathalie, Guieu Régis, Silhol François
Centre for Cardiovascular Research and Nutrition, C2VN, INSERM, INRAE, Aix Marseille University, 13000 Marseille, France.
Hypertension Department, Pôle Cardio-Vasculaire, Timone University Hospital, 13000 Marseille, France.
Biomedicines. 2022 Nov 6;10(11):2831. doi: 10.3390/biomedicines10112831.
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A1, A2A, and A2B receptor production by Western blot, in 67 patients (17 men and 50 women, mean (range) age 55 (29−77) years and 40 controls, 10 men and 30 women, mean (range) age 56 (37−70)). ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7−3) µmol/L vs. controls 0.6 (0.4−0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70 (0.90−2.40; arbitrary units) vs. controls = 1.03 (0.70−1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms.
纤维肌发育不良（FMD）是一种非炎性血管疾病，其特征为年轻人出现不明原因的系统性高血压，伴有动脉狭窄、动脉瘤破裂、颅内/肾梗死和中风。尽管诊断的金标准仍是导管血管造影术，但由于从首次出现症状到诊断存在延迟，生物标志物会有所帮助。腺苷是一种ATP衍生物，可能与FMD的病理生理学有关。我们假设腺苷血水平（ABL）的变化和腺苷受体的产生可能与FMD有关。我们使用外周血单核细胞，通过蛋白质印迹法评估了67例患者（17例男性和50例女性，平均（范围）年龄55（29 - 77）岁）和40例对照者（10例男性和30例女性，平均（范围）年龄56（37 - 70）岁）中A1、A2A和A2B受体的产生情况。通过液相色谱 - 质谱法评估ABL。患者的ABL显著高于对照者，平均（范围）：1.7（0.7 - 3）μmol/L，而对照者为0.6（0.4 - 0.8）μmol/L（增加180%），p < 0.001。虽然患者和对照者中A1R和A2AR的产生没有差异，但我们发现患者中A2BR产生过多：1.70（0.90 - 2.40；任意单位），而对照者为1.03（0.70 - 1.40），平均增加65%（p < 0.001）。以1.3个任意单位为临界值的A2BR产生情况，对诊断具有良好的敏感性和特异性。测量单核细胞上A2BR的产生情况和ABL有助于诊断，尤其是在非典型或症状不明显的情况下。
