title: Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists.
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.
authors.affiliation: Departments of Surgery, Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. miller.virginia@mayo.edu.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kaplan
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Berga
authors.forename: Nanette K
authors.initials: NK
authors.lastname: Wenger
authors.forename: Leslee J
authors.initials: LJ
authors.lastname: Shaw
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
authors.forename: Monica
authors.initials: M
authors.lastname: Mallampalli
authors.forename: Meir
authors.initials: M
authors.lastname: Steiner
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.forename: C Noel Bairey
authors.initials: CN
authors.lastname: Merz
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff