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

• Type of Material: Article
• Authors: Virginia M Miller, Mayo Clinic; Jay R Kaplan, Wake Forest School of Medicine; Nicholas J Schork, The Scripps Research Institute and The Scripps Translational Science Institute; Pamela Ouyang, Johns Hopkins University; Sarah L Berga, Emory University; Nanette K Wenger, Emory University; Leslee J Shaw, Emory University; R Clinton Webb, Georgia Health Sciences University; Monica Mallampalli, Society for Women's Health Research; Meir Steiner, St Joseph's Healthcare; Doris A Taylor, University of Minnesota; C Noel Bairey Merz, Cedars-Sinai Heart Institute; Jane F Reckelhoff, University of Mississippi Medical Center
• Language: English
• Date: 2011-12-12
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: ©2011 Miller et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.crossref.org/10.1186%2F2042-6410-2-14
• Title of Journal or Parent Work: Biology of Sex Differences
• Volume: 2
• Start Page: 14
• End Page: 14
• Grant/Funding Information: This work was made possible by a grant to the Society for Women's Health Research (SWHR) ISIS Cardiovascular Network.; SWHR is a national, non-profit organization headquartered in Washington, DC, USA.; VMM served as President of the Organization for the Study of Sex Differences, an affiliate of SWHR, from 2010 to 2012.
• Keywords: sex chromosomes; testosterone; genomics; sex steroid hormones; animal models; estrogen; gender; study design
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical; Health Sciences, Pathology

Abstract

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.