Racial differences in the responses to shear stress in human umbilical vein endothelial cells
Cell Culture Techniques
European Continental Ancestry Group
Human Umbilical Vein Endothelial Cells
Nitric Oxide Synthase Type III
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/5521
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AbstractBackground: African American ethnicity is an independent risk factor for exaggerated oxidative stress, which is related to inflammation, hypertension, and cardiovascular disease. Recently, we reported that in vitro oxidative stress and inflammation levels differ between African American and Caucasian human umbilical vein endothelial cells (HUVECs), African American HUVECs having higher levels of both. However, it remains to be shown whether the cells would respond differently to external stimuli. Methods: We used a cone and plate viscometer to apply laminar shear stress (LSS) as an aerobic exercise mimetic to compare the responses by race. HUVECs were exposed to static conditions (no LSS), low LSS (5 dyne/cm2), and moderate LSS (20 dyne/cm2). Results: It was found that African American HUVECs had higher levels of oxidative stress under static conditions, and when LSS was applied protein expression levels (NADPH oxidase NOX2, NOX4 and p47phox subunits, eNOS, SOD2, and catalase) and biomarkers (NO, SOD, and total antioxidant capacity) were modulated to similar levels between race. Conclusion: African American HUVECs may be more responsive to LSS stimulus indicating that aerobic exercise prescriptions may be valuable for this population since the potential exists for large in vivo improvements in oxidative stress levels along the endothelial layer in response to increased shear flow. © 2011 Feairheller et al, publisher and licensee Dove Medical Press Ltd.
Citation to related workInforma UK Limited
Has partVascular Health and Risk Management
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Race-Dependent Modulation of Endothelial Cell Responses to Shear Stress: Implications for Vascular Health in African AmericansBrown, Michael D.; Park, Joon Young; Rizzo, Victor; Kendrick, Zebulon V.; Roth, Stephen M., 1973- (Temple University. Libraries, 2011)It is known that African American ethnicity is an independent risk factor for exaggerated oxidative stress which is intricately intertwined with inflammation, hypertension (HT), and cardiovascular disease (CVD). The purpose of this dissertation study was to examine the racial differences that exist between African Americans and Caucasians in oxidative stress levels at the molecular level using an in vitro model of Human Umbilical Vein Endothelial Cells (HUVECs). African American HUVECs were found to have significantly higher baseline levels of oxidative stress in vitro compared to Caucasian HUVECs. In order to establish proof of concept, three preliminary studies were conducted. The first preliminary study, an acute exercise protocol was conducted in young healthy adults in order to measure plasma oxidative stress markers in response to a single moderate intensity treadmill exercise bout. In this study, it was found that the treadmill exercise did not elicit a race-dependent responses, but that African American adults had higher level of oxidative stress at all sample times when compared to the Caucasians. A second preliminary study was conducted using a parallel cell culture design to measure basal oxidative stress levels in African American and Caucasian HUVECs without stimulation. These data were shown in relation to the plasma levels of oxidative stress in resting African American and Caucasian adults. This was done in order to show that the common oxidative stress markers measured in human plasma can also be measured in cell culture supernatant and lysate. It was found that both African American adults and HUVECs had heightened oxidative stress and inflammatory markers when compared to their Caucasian counterparts. The third preliminary study was conducted using tumor Necrosis Factor-#945; (TNF-#945;) as an inflammatory stimulant and measuring the oxidative stress response in both African American and Caucasian HUVECs. This was done in order to show that cells of different race respond differently to stimuli. It was found that the response to TNF-α was blunted in African American HUVECs. The final step was to use laminar shear stress (LSS) as an exercise mimetic in order to examine whether HUVECs from different race respond differently. HUVECs from both race were harvested under static condition (no LSS), with low LSS at 5 dyne/cm2, and with a moderate level of LSS at 20 dyne/cm2. It was found that despite the fact that African American HUVECs had higher levels of oxidative stress under static conditions, when LSS was applied, protein expressions and oxidative stress biomarkers adjusted to levels that were similar to the Caucasian HUVEC adaptations to LSS. From this, it appears that African American HUVECs have a larger response to LSS stimulus indicating that aerobic exercise prescriptions may be valuable for this population since the potential exists for large improvements in oxidative stress levels for this population.
Social status modulating chronic stress: Social rank differentially influences how male and female mice respond to chronic stress.Bangasser, DA; Sanchez, EO (2020-10-01)<jats:p>Social rank differentially influences how male and female mice respond to chronic stress.</jats:p>
Sex differences in corticotropin-releasing factor receptor signaling and trafficking: Potential role in female vulnerability to stress-related psychopathologyBangasser, DA; Curtis, A; Reyes, BAS; Bethea, TT; Parastatidis, I; Ischiropoulos, H; Van Bockstaele, EJ; Valentino, RJ (2010-09-01)Although the higher incidence of stress-related psychiatric disorders in females is well documented, its basis is unknown. Here, we show that the receptor for corticotropin-releasing factor (CRF), the neuropeptide that orchestrates the stress response, signals and is trafficked differently in female rats in a manner that could result in a greater response and decreased adaptation to stressors. Most cellular responses to CRF in the brain are mediated by CRF receptor (CRFr) association with the GTP-binding protein, G s. Receptor immunoprecipitation studies revealed enhanced CRFr-G s coupling in cortical tissue of unstressed female rats. Previous stressor exposure abolished this sex difference by increasing CRFr-Gs coupling selectively in males. These molecular results mirrored the effects of sex and stress on sensitivity of locus ceruleus (LC)-norepinephrine neurons to CRF. Differences in CRFr trafficking were also identified that could compromise stress adaptation in females. Specifically, stress-induced CRFr association with Β-arrestin2, an integral step in receptor internalization, occurred only in male rats. Immunoelectron microscopy confirmed that stress elicited CRFr internalization in LC neurons of male rats exclusively, consistent with reported electrophysiological evidence for stress-induced desensitization to CRF in males. Together, these studies identified two aspects of CRFr function, increased cellular signaling and compromised internalization, which render CRF-receptive neurons of females more sensitive to low levels of CRF and less adaptable to high levels of CRF. CRFr dysfunction in females may underlie their increased vulnerability to develop stress-related pathology, particularly that related to increased activity of the LC-norepinephrine system, such as depression or post-traumatic stress disorder. © 2010 Macmillan Publishers Limited All rights reserved.