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Published on: June 3, 2019
Gender differences in age-related endothelial function in the murine aorta
Yasuhiro Takenouchi1, Tsuneo Kobayashi, Takayuki Matsumoto
1Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Atherosclerosis
|April 10, 2009
Summary
Aging impairs aortic endothelial function in male mice due to increased superoxide production, while female mice show preserved function with enhanced superoxide scavenging mechanisms.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Endothelial Function
Background:
- Aging is associated with endothelial dysfunction, increasing cardiovascular disease risk.
- Sex differences in aging cardiovascular effects are not fully understood.
- Oxidative stress plays a key role in age-related endothelial dysfunction.
Purpose of the Study:
- To investigate age- and sex-dependent differences in mouse aortic endothelial function.
- To explore the underlying mechanisms, including oxidative stress and antioxidant enzyme activity.
Main Methods:
- Comparison of aortic relaxation and superoxide generation in young (5 months) and old (20 months) male and female mice.
- Measurement of NAD(P)H oxidase subunit (gp91phox) expression.
- Assessment of plasma adiponectin and aortic superoxide dismutase (SOD) enzyme expression and activity.
- Pharmacological interventions with NAD(P)H oxidase substrates/inhibitors and SOD mimetics.
Main Results:
- Old male mice exhibited impaired aortic relaxation and increased superoxide generation compared to young males and old females.
- NAD(P)H oxidase subunit gp91phox expression was upregulated in aortas of old mice.
- Female mice, regardless of age, had higher plasma adiponectin and aortic Cu/Zn-SOD and EC-SOD expression than age-matched males.
- Old male aortas showed reduced total SOD activity, while Tempol (SOD mimetic) improved relaxation and reduced superoxide generation.
Conclusions:
- Impaired endothelium-dependent aortic relaxation in old male mice is primarily driven by enhanced superoxide production via NAD(P)H oxidase.
- Preserved endothelial function in old female mice may be attributed to increased superoxide scavenging capacity through elevated SOD enzymes.
