ABSTRACT
Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.
ABSTRACT
Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts aiming to help predict metastatic propensities to organ-specific sites in a clinical setting.
