Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

BACKGROUND: Epicardial adipose tissue expresses adiponectin protein, and its expression is significantly lower in patients with severe coronary artery disease (CAD) than in those without CAD. Transcoronary adiponectin levels are significantly decreased in nondiabetic but not in diabetic patients with CAD. Adiponectin is also an important adipocytokine that is linked to insulin resistance and reduces coronary microvascular function. HYPOTHESIS: Adiponectin may play a significant role in the localized coronary circulation. The present study examines the local dynamics of adiponectin in the coronary circulation in nondiabetic individuals with normal coronary arteries and the relationship between adiponectin and coronary microvasculature function. METHODS: We examined 22 consecutive nondiabetic patients whose coronary arteries were angiographically normal. Plasma levels of adiponectin were measured in blood samples that were simultaneously collected from the orifice of the left coronary artery (LCA) and the great cardiac vein (GCV). To evaluate the function of the coronary microcirculation, we measured coronary flow velocity at maximal hyperemia using a Doppler wire. Coronary flow reserve (CFR) was obtained from the ratio of hyperemia to the baseline coronary flow velocity. RESULTS: Plasma adiponectin levels in the GCV (median 6.95 microg/ml) were significantly higher than those in the LCA (median 6.60 microg/ml, p < 0.0005). The difference in plasma adiponectin levels between GCV and LCA significantly correlated with CFR (R = 0.451, p < 0.05). CONCLUSIONS: Adiponectin is locally produced in the coronary circulation. This protein may participate in modulating the coronary circulation of nondiabetic patients with angiographically normal coronary arteries.