Aortic Segments-Depending Hypertensive Remodeling Is Driven by Mitochondrial Fusion Dysfunction

OPA1 haploinsufficiency exacerbates severe hypertension-induced aortic remodeling in a segment-specific manner, revealing differential vulnerability between the suprarenal abdominal aorta (SRAA) and the descending thoracic aorta (DTA). In the SRAA, hypertension activates mitochondrial fission pathways (DRP1, FIS1) and mitophagy markers (PINK1, PARKIN), without triggering full autophagic flux (LC3B, p62). Respiratory chain complexes I and IV are upregulated in hypertensive Opa1+/− mice across both segments, reflecting a compensatory mitochondrial stress response. Apoptotic analysis shows increased TUNEL staining in both regions, while caspase-3 and 9 activation is restricted to the SRAA. Inflammatory profiling reveals a predominance of M1 macrophages, specifically in the SRAA. Morphometric assessment highlights major impacts in SRAA, such as luminal dilation and adventitial thickening, confirmed by in vivo representative ultrasound images. These findings underscore the pivotal role of OPA1 in mitochondrial homeostasis and reveal, for the first time, a region-specific protective function of OPA1 within the aortic wall under severe hypertensive stress. This differential impact, according to aortic segment anatomy and physiology, opens new avenues for hypertension and pathological aorta remodeling therapies.