Sex and sex hormones in cardiac stress—Mechanistic insights

Bell, James; Bernasochi, Gabriel B.; Varma, Upasna; Raaijmakers, A.; Delbridge, L.

doi:10.1016/j.jsbmb.2013.05.015

Cited by 83 publications

(76 citation statements)

References 154 publications

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“…As we know, testosterone can be converted into E 2 by aromatase in the local tissue without increasing serum E 2 levels (Simpson 2003, Bell et al 2013. In order to completely exclude the effect of E 2 , in the next step we will use testosterone plus an aromatase inhibitor and analyze the expression of progesterone receptor, which was considered to be a highly estrogen-dependent gene (Comeglio et al 2014), within myocardial tissue.…”

Section: Discussionmentioning

confidence: 99%

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Wang¹,

Yang²,

Sun³

et al. 2015

Journal of Endocrinology

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Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

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Section: Discussionmentioning

confidence: 99%

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Wang¹,

Yang²,

Sun³

et al. 2015

Journal of Endocrinology

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“…In our study, ANOVA indicated that blood lipid levels and parameters of echocardiography among individuals with different genotypes did not differ between CHD patients and control participants. These results suggest that aromatase may affect the heart function through mechanisms other than those involving lipid metabolism, and recent studies in animals have shown that testosterone and estrogen have contrasting inotropic actions and modulate Ca(2+) handling and transient characteristics (Bell et al, 2013). We intend to further investigate feasible mechanisms underlying the effects of aromatase in the cardiovascular system through studies in cells and animal models.…”

Section: Discussionmentioning

confidence: 91%

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease

Wang

et al. 2016

Genetic Testing and Molecular Biomarkers

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Objective: An imbalance in sex hormone ratios has been identified in coronary heart disease (CHD), and as a key enzyme in the conversion of androgen to estrogen, aromatase plays an important role in the balance of sex hormone levels. However, there is a paucity of research into the potential roles of aromatase in CHD. In this study, we investigated associations between single-nucleotide polymorphisms (SNPs) in the CYP19 gene, which encodes aromatase, and CHD. Methods: We collected 1706 blood samples from CHD patients and control participants and used propensity score matching techniques to match case and control groups with respect to confounding factors. In a final study population, including 596 individuals, we conducted a case-control study to identify associations between three SNPs in CYP19 and CHD using v 2 or Fisher exact tests, and binary logistic regression analysis. Differences in lipid levels and parameters of echocardiography among individuals with different genotypes were assessed by one-way analysis of variance. Results: The distributions of rs2289105 alleles in the CYP19 gene differed significantly between the CHD and control groups ( p = 0.014), and the heterozygote CT genotype was associated with a significantly lower risk of CHD compared to the homozygous wild-type CC genotype ( p = 0.0063 and odds ratio = 0.575). However, blood lipid levels and echocardiographic parameters among individuals with different genotypes did not differ between the CHD and control groups. Conclusions: The CT genotype of the rs2289105 polymorphism in the CYP19 gene is associated with a decreased risk of CHD and may be a genetic marker of protection from CHD.

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“…Furthermore, many studies investigating actions of sex steroids have been designed to examine testosterone in males and estrogen in females. However, aromatization of testosterone to estrogen in males has cardiovascular consequences, [26][27][28][29][30][31] and cardiovascular effects of testosterone and its aromatization in women have not been studied systematically. Additional investigation into mechanisms of action for both of these hormones in both sexes is needed, as hormonal supplementation continues to be used clinically.…”

Section: Millermentioning

confidence: 99%

Congress on Women's Health Trudy Bush Lecture 2014: New Insights into Sex Hormones and Cardiovascular Disease

Miller

2014

Journal of Women's Health

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SummaryMany basic, mechanistic studies of how sex steroids alter vascular function proceeded from Dr. Bush's seminal epidemiologic observations that noncontraceptive use of estrogen reduced all-cause and cardiovascular mortality. However, translating findings from these basic science studies into clinical trials and clinical guidelines has been controversial. This commentary reviews the development of sex steroid vascular research, identifies mechanisms by which sex steroids affect vascular function, reviews findings from recent clinical hormone trials, and identifies challenges and the need for continued funding of such investigations.

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Sex and sex hormones in cardiac stress—Mechanistic insights

Cited by 83 publications

References 154 publications

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease

Congress on Women's Health Trudy Bush Lecture 2014: New Insights into Sex Hormones and Cardiovascular Disease

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