title: The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease.
abstract: Nearly one-third of deaths in the United States are caused by cardiovascular disease (CVD) each year. In the past, CVD was thought to mainly affect men, leading to the exclusion of women and female animals from clinical studies and preclinical research. In light of sexual dimorphisms in CVD, a need exists to examine baseline cardiac differences in humans and the animals used to model CVD. In humans, sex differences are apparent at every level of cardiovascular physiology from action potential duration and mitochondrial energetics to cardiac myocyte and whole-heart contractile function. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. Although endogenous estrogen is most likely a mediator of the observed functional differences in both health and disease, the signaling mechanisms involved are complex and are not yet fully understood. To investigate how sex modulates CVD development, animal models are essential tools and should be useful in the development of therapeutics. This review will focus on describing the cardiovascular sexual dimorphisms that exist both physiologically and in common animal models of CVD.
authors.affiliation: From the Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado, Boulder (C.L.B., P.A.H., L.A.L.); and Women's Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.F.R.).
authors.forename: Christa L
authors.initials: CL
authors.lastname: Blenck
authors.affiliation: From the Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado, Boulder (C.L.B., P.A.H., L.A.L.); and Women's Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.F.R.).
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Harvey
authors.affiliation: From the Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado, Boulder (C.L.B., P.A.H., L.A.L.); and Women's Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.F.R.).
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
authors.affiliation: From the Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado, Boulder (C.L.B., P.A.H., L.A.L.); and Women's Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.F.R.). leslie.leinwand@colorado.edu.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000502:physiology; D051381:Rats; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004967:Estrogens
keywords: cardiovascular diseases; estrogens; gonadal steroid hormones; heart failure; sex characteristics