Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists

Biology of Sex Differences

Virginia M Miller⁴  Jay R Kaplan⁷  Nicholas J Schork¹³  Pamela Ouyang⁶  Sarah L Berga⁸  Nanette K Wenger¹¹  Leslee J Shaw¹⁰  R Clinton Webb¹²  Monica Mallampalli²  Meir Steiner¹  Doris A Taylor⁵  C Noel Bairey Merz³  Jane F Reckelhoff⁹ 

[1] St Joseph's Healthcare, Hamilton, Ontario, Canada

[2] Science Department, Society for Women's Health Research, Washington, DC, USA

[3] Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA

[4] Departments of Surgery, Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

[5] Department of Integrative Biology and Physiology, Center for Cardiovascular Repair, University of Minnesota, Minneapolis, MN, USA

[6] Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

[7] Department of Pathology (Comparative Medicine), Wake Forest School of Medicine, Winston-Salem, NC, USA

[8] Department of Obstetrics and Gynecology, Wake Forest University, Winston-Salem, NC, USA

[9] Women's Health Research Center and Department of Physiology and Biophysics University of Mississippi Medical Center, Jackson, MS, USA

[10] Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA

[11] Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA

[12] Department of Physiology, Georgia Health Sciences University, Augusta, GA, USA

[13] The Scripps Research Institute and The Scripps Translational Science Institute, La Jolla, CA, USA

关键词: testosterone;    study design;    sex steroid hormones;    sex chromosomes;    genomics;    gender;    estrogen;    animal models;   

Others  :  793844
DOI  :  10.1186/2042-6410-2-14

 received in 2011-07-21, accepted in 2011-12-12,  发布年份 2011

【 摘 要 】

Background

Cardiovascular disease remains the primary cause of death worldwide. In the US, deaths due to cardiovascular disease for women exceed those of men. While cultural and psychosocial factors such as education, economic status, marital status and access to healthcare contribute to sex differences in adverse outcomes, physiological and molecular bases of differences between women and men that contribute to development of cardiovascular disease and response to therapy remain underexplored.

Methods

This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease.

Results

To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration.

Conclusions

Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.

【 授权许可】

   
2011 Miller et al; licensee BioMed Central Ltd.

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