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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Altered endothelial mitochondrial Opa1-related fusion in mouse accelerates age-associated vascular and kidney damage
Carlotta Turnaturi1,2, Loïck L'Hoste1,3, Coralyne Proux1
1Univ Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT, Angers, France.
Insights
Reduced optic atrophy type 1 (Opa1) in endothelial cells accelerates vascular aging and kidney oxidative stress. This mitochondrial fusion protein is crucial for maintaining vascular health and protecting against age-related damage.
Area of Science:
- Cardiovascular biology
- Mitochondrial biology
- Aging research
Background:
- Cardiovascular diseases are a leading cause of death, often exacerbated by aging and kidney damage.
- Reduced optic atrophy type 1 (Opa1) in endothelial cells (ECs) impairs vascular function and increases oxidative stress.
- Opa1's role in vascular aging, particularly in the context of kidney health, requires further investigation.
Purpose of the Study:
- To investigate the hypothesis that reduced Opa1 expression in ECs contributes to vascular aging.
- To examine the impact of EC-specific Opa1 deficiency on vascular reactivity and kidney oxidative stress markers in aging mice.
Main Methods:
- Utilized male and female mice with EC-specific Opa1 knock-out (EC-Opa1) and wild-type (EC-WT) littermates at young (6 months) and old (20 months) ages.
- Assessed vascular reactivity of mesenteric resistance arteries (MRAs) and analyzed kidney tissues via western-blot.
- Quantified levels of key proteins related to mitochondrial dynamics, oxidative stress, and endothelial function.
Main Results:
- Old EC-Opa1 mice exhibited elevated blood urea and reduced endothelium-dependent relaxation in MRAs compared to old EC-WT mice.
- Increased levels of mitochondrial fission protein (Fis-1) and Pgc-1α were observed in the kidneys of old EC-Opa1 mice.
- Elevated expression of caveolin-1 and NADPH oxidase subunit gp91 was detected in kidneys of old EC-Opa1 mice, indicating increased oxidative stress.
Conclusions:
- Reduced mitochondrial fusion in mouse ECs negatively impacts mesenteric vascular reactivity and exacerbates oxidative stress markers in aging kidneys.
- Opa1 plays a protective role in the vascular tree of vital organs, including the kidney, against age-related decline.
- Targeting Opa1 in ECs may offer therapeutic potential for mitigating vascular aging and associated kidney damage.
Abstract:
Cardiovascular diseases are the major cause of death worldwide, and their frequency increases with age in association with kidney damage. As a reduction in fusion protein optic atrophy type 1 (Opa1) level in endothelial cells (ECs) decreases the vascular response to flow and increases oxidative stress in perfused kidneys, we hypothesized that reduced Opa1 expression contributes to vascular aging. We used male and female mice with ECs specific Opa1 knock-out (EC-Opa1), and littermate wild-type (EC-WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and western-blot analysis. In old EC-Opa1 mice, blood urea was greater than in EC-WT mice, and MRA showed reduced endothelium-dependent relaxation. In kidneys, the mitochondria fission protein fission-1 (Fis-1) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were increased in old EC-Opa1 mice. The level of caveolin-1 expression was greater in old EC-Opa1 mice. Moreover, in kidneys from EC-Opa1 old mice, NADPH-oxidase subunit gp91 expression was greater than in age-matched EC-WT mice. Thus, reduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased markers of oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney.
