Abstract
We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3, Beclin1, and P62 protein levels via western blotting. The autophagy flux was detected by confocal microscopy and transmission electron microscopy. For in vivo experiments, spontaneously hypertensive rats were orally administered with IBAN. Utilizing angiotensin II (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) as a model of endothelial cell injury in hypertension, we found that IBAN promoted autophagy and protected cell viability in Ang II-treated-endothelial cells while these effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells.