Aortic Segments‐Depending Hypertensive Remodeling Is Driven by Mitochondrial Fusion Dysfunction
Abstract
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.
| IntroductionArterial hypertension, a major risk factor for global morbidity and mortality, is closely linked to arterial remodeling. Hypertension induced-inward eutrophic remodeling affects resistance arteries, compromising vasomotricity, myogenic tone, and flow-mediated dilation, ultimately leading to elevated peripheral resistance, while conductance arteries show a hypertrophic outward remodeling, resulting in increased vascular rigidity and pulse wave velocity, further exacerbating
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BibTeX
@article{richard2026aortic,
title = {{Aortic Segments‐Depending Hypertensive Remodeling Is Driven by Mitochondrial Fusion Dysfunction}},
author = {Alexis Richard and Alicia Baptista Vicente and Clara Gourhand and Antoine Ducroix and Pauline Robert and Bertrand Toutain and Linda Grimaud and Emilie Vessières and Agnès Toutain‐barbelivien and Guy Lenaers and Juan‐manuel Chao de la Barca and Olivier Fouquet and Daniel Henrion and Céline Fassot and Laurent Loufrani},
journal = {FASEB Journal},
year = {2026},
month = may,
doi = {10.1096/fj.202503667r},
url = {https://univ-angers.hal.science/hal-05732360v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Aortic Segments‐Depending Hypertensive Remodeling Is Driven by Mitochondrial Fusion Dysfunction
AU - Alexis Richard
AU - Alicia Baptista Vicente
AU - Clara Gourhand
AU - Antoine Ducroix
AU - Pauline Robert
AU - Bertrand Toutain
AU - Linda Grimaud
AU - Emilie Vessières
AU - Agnès Toutain‐barbelivien
AU - Guy Lenaers
AU - Juan‐manuel Chao de la Barca
AU - Olivier Fouquet
AU - Daniel Henrion
AU - Céline Fassot
AU - Laurent Loufrani
PY - 2026
DA - 2026/05/22
JO - FASEB Journal
DO - 10.1096/fj.202503667r
UR - https://univ-angers.hal.science/hal-05732360v1
AB - 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. | IntroductionArterial hypertension, a major risk factor for global morbidity and mortality, is closely linked to arterial remodeling. Hypertension induced-inward eutrophic remodeling affects resistance arteries, compromising vasomotricity, myogenic tone, and flow-mediated dilation, ultimately leading to elevated peripheral resistance, while conductance arteries show a hypertrophic outward remodeling, resulting in increased vascular rigidity and pulse wave velocity, further exacerbating
SN - 0892-6638
SN - 1530-6860
ER -