Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity

Quercioli, Alessandra ; Pataky, Zoltan ; Vincenti, Gabriella ; Makoundou, Vincent ; Di Marzo, Vincenzo ; Montecucco, Fabrizio ; Carballo, Sebastian ; Thomas, Aurélien ; Staub, Christian ; Steffens, Sabine ; Seimbille, Yann ; Golay, Alain ; Ratib, Osman ; Harsch, Elisabetta ; Mach, François ; Schindler, Thomas H.

In: European Heart Journal, 2011, vol. 32, no. 11, p. 1369-1378

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    Summary
    Aims Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. Methods and results Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with 13N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m2): control group 20≤ BMI <25 (n = 21); overweight group, 25≤ BMI <30 (n = 26); and obese group, BMI ≥30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (−0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = −0.37, P = 0.046 and r = −0.48, P = 0.008) and hyperaemic MBFs (r = −0.38, P = 0.052 and r = −0.45, P = 0.017), respectively. Conclusions Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations