Adiponectin Protects Against Angiotensin II or Tumor Necrosis Factor α–Induced Endothelial Cell Monolayer Hyperpermeability Role of cAMP/PKA Signaling

Objective— Angiotensin II (Ang II) and tumor necrosis factor (TNF)-α levels increase endothelial permeability, and we hypothesized that adiponectin suppressed these responses in a cAMP-dependent manner. Methods and Results— The effect of adiponectin on transendothelial electric resistance (TEER) and diffusion of albumin through human umbilical vein and bovine aortic endothelial cell monolayers induced by Ang II (100 nmol/L) or TNF-α (5 ng/mL) was measured. Treatment with the globular domain of adiponectin (3 μg/mL) for 16 hours abrogated the adverse TEER effect of TNF-α (−35 versus −12 Ω/cm 2 at 45 minutes, P 2 at 45 minutes, P P P Conclusions— Adiponectin protects the endothelial monolayer from Ang II or TNF-α-induced hyperpermeability by modulating microtubule and cytoskeleton stability via a cAMP/ PKA signaling cascade.