Beta-adrenoceptor agonists and other cAMP elevating agents suppress PAI-1 production of human adipocytes in primary culture

Recent studies showed that catecholamines contribute to the regulation of plasminogen activator inhibitor-1 (PAI-1) expression, at least in endothelial cells. Aim of this study was to examine the role of catecholamines on PAI-1 production by human adipocytes and, in particular, to clarify which adrenoceptor (AR) subtypes are involved. Addition of the unselective AR agonist isoproterenol led to a dose- and time-dependent suppression of PAI-1 mRNA and protein release in adipocytes from the subcutaneous and omental depot of obese subjects. A similar degree of suppression was observed in subcutaneous mammary adipocytes of lean women. This effect was mainly mediated via the β₂-adrenoceptor according to experiments using selective agonists. Moreover, addition of cAMP-elevating agents such as dibutyryl-cAMP, forskolin and the phosphodiesterase inhibitors isobutyl-methylxanthine and milrinone resulted in a reduction of PAI-1 of varying degrees. In conclusion, the results of this study support the assumption that catecholamines are able to downregulate PAI-1 expression and secretion in human adipocytes via β-adrenergic receptors.