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Review
. 2017 May;21(5):1024-1032.
doi: 10.1111/jcmm.13038. Epub 2016 Dec 13.

Gender difference in oxidative stress: a new look at the mechanisms for cardiovascular diseases

Melissa Christine Kander  1 , Yuqi Cui  1 , Zhenguo Liu  1
Affiliations
Review

Gender difference in oxidative stress: a new look at the mechanisms for cardiovascular diseases

Melissa Christine Kander et al. J Cell Mol Med. 2017 May.

Abstract

Gender differences are present in many diseases and are especially prevalent in cardiovascular disease. Males tend to suffer from myocardial infarctions earlier than females, and a woman's risk of cardiovascular disease increases after menopause, suggesting a cardio-protective role of estrogen. However, hormone replacement therapy did not decrease the risk of cardiovascular disease in post-menopausal women; thus, other mechanisms may be involved besides estrogen. Oxidative stress plays an important role in the development of cardiovascular diseases such as coronary artery disease. Gender is also associated with differences in oxidative stress. Under physiological conditions, females appear to be less susceptible to oxidative stress. This may be due to the antioxidant properties of estrogen, gender differences in NADPH-oxidase activity or other mechanism(s) yet to be defined. This review strives to discuss gender differences in general terms followed by a more detailed examination of gender differences with oxidative stress and various associated diseases and the possible mechanisms underlying these differences.

Keywords: cardiovascular disease; gender; oxidative stress.

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Figures

Figure 1
Figure 1
Male and female differences in hypertrophy and ischaemia–reperfusion injury. (A) In an animal study with mice, females were shown to have lower levels of hypertrophy than males. Figure adapted from Skavdahl et al. 16. (B) In a global ischaemia model of rat hearts, females were shown to have a smaller percentage of infarct than males. Figure adapted from Bae and Zhang 17.
Figure 2
Figure 2
Cardiovascular risk factors and gender. (A) Diabetic females have an increased risk of developing coronary artery disease compared to diabetic males. Both diabetic males and females have an increased risk of cardiovascular disease compared to non‐diabetics. This figure was modified from Goldschmid et al. 19. (B) Pre‐menopausal women have lower levels of total cholesterol than men. Levels in post‐menopausal women though rise and exceed that of age‐matched men. Figure modified from Brown et al. 20.
Figure 3
Figure 3
(A) Antioxidant Enzymes. NADPH‐oxidase (‘Nox’ subunits) and eNOS both contribute to the production of superoxide. Superoxide is broken down to hydrogen peroxide by superoxide dismutase (SOD). Hydrogen peroxide is metabolized to water and oxygen by either catalase or GPx. Any imbalance in this anti‐oxidant system could lead to increases in oxidative stress. (B) Mechanisms of Gender Differences in NADPH‐Oxidase. Normally, angiotensin II binds to the angiotensin type 1 receptor (AT1), ultimately resulting in p47 phosphorylation. P47 then travels to the plasma membrane participating in the assembly of the NADPH‐oxidase complex, allowing for superoxide production. Females have lower levels of p47 both in the cytoplasm and at the cell membrane, leading to lower levels of superoxide production (not dependent on estrogen). Females also have lower levels of NADPH‐oxidase activity (may be estrogen‐dependent, depicted as the Nox subunit). The ultimate result of these gender differences is lower levels of superoxide in females with lower levels of oxidative stress and decreased cardiovascular disease risk.
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