Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway.
BACKGROUND
Adiponectin (APN), an adipocytokine, exerts protective effects on cardiac remodeling, while angiotensin II (Ang II) induces hypertension and vascular remodeling. The potential protective role of APN on the vasculature during hypertension has not been fully elucidated yet. Here, we evaluate the molecular mechanisms of the protective role of APN in the physiological response of the vascular wall to Ang II.


RESULTS
Rat aortic tissues were used to investigate the effect of APN on Ang II-induced vascular remodeling and hypertrophy. We investigated whether nitric oxide (NO), the RhoA/ROCK pathway, actin cytoskeleton remodeling, and reactive oxygen species (ROS) mediate the anti-hypertrophic effect of APN. Ang II-induced protein synthesis was attenuated by pre-treatment with APN, NO donor S-nitroso-N-acetylpenicillamine (SNAP), or cGMP. The hypertrophic response to Ang II was associated with a significant increase in RhoA activation and vascular force production, which were prevented by APN and SNAP. NO was also associated with inhibition of Ang II-induced phosphorylation of cofilin. In addition, immunohistochemistry revealed that 24 h Ang II treatment increased the F- to G-actin ratio, an effect that was inhibited by SNAP. Ang II-induced ROS formation and upregulation of p22(phox) mRNA expression were inhibited by APN and NO. Both compounds failed to inhibit Nox1 and p47(phox) expression.


CONCLUSIONS
Our results suggest that the anti-hypertrophic effects of APN are due, in part, to NO-dependent inhibition of the RhoA/ROCK pathway and ROS formation.
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of BeirutBeirut, Lebanon; ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, The Lebanese UniversityBeirut, Lebanon.
Wared
W
Nour-Eldine
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut Beirut, Lebanon.
Crystal M
CM
Ghantous
ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, The Lebanese University Beirut, Lebanon.
Kazem
K
Zibara
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut Beirut, Lebanon.
Leila
L
Dib
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of BeirutBeirut, Lebanon; ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, The Lebanese UniversityBeirut, Lebanon.
Hawraa
H
Issaa
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville TN, USA.
Hana A
HA
Itani
ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, The Lebanese University Beirut, Lebanon.
Nabil
N
El-Zein
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut Beirut, Lebanon.
Asad
A
Zeidan
VSMC; adiponectin; angiotensin II; nitric oxide; remodeling