| Outline of Final Research Achievements |
Angiotensin II(AngII) has a crucial role in cardiovascular pathologies. However, the precise molecular mechanism underlying aging-related endothelial inflammation induced by AngII remains elusive. We have tested a hypothesis in cultured rat aortic endothelial cells (ECs) that the removal of AngII-induced senescent cells, preservation of proteostasis, or inhibition of mitochondrial fission attenuates the pro-inflammatory EC phenotype. AngII stimulation in ECs resulted in cellular senescence. The AngII-induced senescence was attenuated by treatment with a senolytic drug, an ER stress inhibitor, or a mitochondrial fission inhibitor. Pro-inflammatory phenotype in EC induced by AngII was alleviated by these treatments. These findings suggest that mitochondrial fission and endoplasmic reticulum stress have causative roles in endothelial senescence-associated inflammatory phenotype induced by AngII exposure, thus providing potential therapeutic targets in age-related cardiovascular diseases.
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