Ang II-induced abdominal aortic aneurysm
To determine the roles of ER stress in trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-high fat diet (HFD)-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metabolic reprogramming and induced stronger inflammation in AA than in TA; 2) Most of the upregulated genes in the AA and TA are not overlapped and pyroptosis signaling with IL-1B and caspase-4 were more upregulated in Ang II-AA than in TA; 3) Gene KO transcriptomes indicated that ER stress regulator ATF6 and PERK played more significant roles than IRE1 in promoting AAA and trained immunity. Our unprecedented ER-focused transcriptomic analyses have provided novel insights into the roles of ER as an immune organelle in sensing various DAMPs and initiating ER stress that triggers Ang II-accelerated trained immunity and differs susceptibilities of thoracic and abdominal aortas to diseases.