Browsing by Subject "Cardiovascular Diseases"
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Item ApoE, ApoER2, and the Regulation of Endothelial Cell Function(2013-04-02) Ulrich, Victoria; Thorpe, Philip E.; Yanagisawa, Hiromi; Herz, Joachim; Shaul, Philip W.; Mineo, ChiekoCardiovascular disease risk is greater in individuals with the apolipoprotein E (ApoE) allele ApoE4 versus ApoE3, and this is not explained by differences in lipid profiles. A point mutant of the ApoE receptor ApoER2, ApoER2-R952Q, is also associated with greater cardiovascular disease risk, suggesting a role for ApoER2 in vascular health and disease. However, how ApoE, ApoER2, and their variants influence cardiovascular health and disease is poorly understood. We discovered in cultured endothelial cells that ApoE3 activates endothelial NO synthase (eNOS) and thereby stimulates endothelial cell migration, and that both processes require ApoER2. In contrast, ApoE4 is incapable of activating eNOS and in fact blunts ApoE3 activation of eNOS migration. In eNOS-expressing 3T3 cells, we also found that in contrast to wild-type ApoER2, ApoER2-R952Q is incapable of mediating ApoE3 activation of eNOS. Furthermore, we have determined that LDLR-/-;ApoER2-/- mice have markedly worse atherosclerosis than LDLR-/-, and in preliminary studies ApoER2-/- have impaired reendothelialization. The Overall Goal of this project is to determine how ApoE, ApoER2 and their variants influence endothelial cell function, and the implications of these processes in vascular health and disease. The first aim is to identify the molecular basis for ApoE-ApoER2 function in endothelial cells. The roles of adaptor proteins for ApoER2 and for kinase signaling in ApoE3/ApoER2 activation of eNOS were tested. The basis for impaired signaling by ApoE4 will also be explored. The second aim is to determine how ApoE and ApoER2 influence endothelial cell phenotype in vivo. Carotid artery reendothelialization after perivascular electric injury were compared in wild-type, human ApoE3-expressing, and ApoE4-expressing mice. The third aim is to determine the role of endothelial cell ApoER2 in atheroprotection. We have successfully created floxed ApoER2 mice, and atherosclerosis development will be evaluated in crosses of ApoER2flox/flox with endothelial cell-expressing Cre and LDLR-/- mice in the future. From the unique perspective of apolipoprotein signaling in endothelium, the proposed work will enhance our fundamental understanding of ApoE and ApoER2 in cardiovascular health and disease.Item Broken hearts and blue beans: depression in heart and kidney disease(2006-10-06) Hedayati, SusanItem Can we stop the tsunami of common, chronic disease in the post-pandemic era?(2021-04-16) Califf, Robert M.Item The cardiac channelopathies can the molecular tale wag the clinical dog?(2003-05-29) Kowal, Robert C.Item Cardioembolic stroke(1994-10-27) Brickner, BethItem Cardiovascular aging: genes, gender and grumpiness(1997-12-18) Benjamin, Ivor J.Item Cardiovascular gene therapy: Angiogenesis and beyond(2003-06-05) Shohet, Ralph V.Item Cardiovascular outcomes in ESRD: can we do better(2005-04-07) Dev, Devasmita C.Item Cardiovascular Risk Factors Predict the Spatial Distribution of White Matter Hyperintensities(2014-02-04) Banerjee, Soham; King, Kevin; McColl, Roderick; Whittemore, Anthony; Hulsey, Keith; Peshock, Ronald M.PURPOSE: Increased volume of brain white matter hyperintensities (WMH) seen on MRI is associated with cardiovascular risk factors; however, WMH have also been attributed to normal aging. Recent studies have suggested that WMH in some brain regions are more strongly associated with specific risk factors. The purpose of this study was to create a map of every individual brain voxel that was significantly associated with risk factors (hypertension, diabetes, hyper-cholesterolemia) as compared to those without each risk factor. The aim of the study is to create a predictive model, which uses the WMH distribution to determine the associated underlying risk factor. METHODS: The MRI brain images used for analysis were obtained from 2066 participants in the Dallas Heart Study, a population based study. Each MRI brain was transformed onto a standard template that adjusts for participant variation in brain volume and shape, using the FSL SIENAX software. The participant's WMH distributions were then generated from their MRIs using an automated algorithm. For each risk factor, the subjects were divided into a case group and a control group. Each voxel of WMH was compared between the two groups using a two tailed nonparametric permutation test. A map of every voxel significantly associated with each risk factor was created. RESULTS: Of the total of 431891 voxels that comprise the distribution of WMH over the entire population, 26064 voxels (6%) were significantly associated with hypertension only. These hypertensive-associated voxels were prevalent anterior to the frontal horns of the lateral ventricles. Similarly, 22527 voxels (5%) were associated with diabetes only with a prevalence near the longitudinal cerebral fissure as well as lateral to the posterior horns of the lateral ventricles. 8088 voxels (2%) were associated with hyper-cholesterolemia only and were abundant posterior to the posterior horns of the lateral ventricles. 331588 voxels (77%) were not associated with a risk factor. CONCLUSIONS: For hypertension, diabetes, and hyper-cholesterolemia, certain voxels were significantly associated with a risk factor, and maps of these voxels were created. Knowing the WMH distribution significantly associated with each risk factor will improve the specificity for evaluating patients for risk factor associated white matter injury. Importantly, this approach makes no a priori assumptions which divide the brain into functional regions or vascular territories.Item Cardiovascular Risk Factors Predict the Spatial Distribution of White Matter Hyperintensity(2015-03-24) Banerjee, Soham; McColl, Roderick W.; Whittemore, Anthony W.; Hulsey, Keith M.OBJECTIVES: To identify the different spatial distribution of white matter hyperintensity (WMH) associated with specific risk factors and use this distribution to estimate the extent of risk factor associated WMH in an individual. MATERIALS AND METHODS: MRI brain images were obtained from 2066 healthy adult participants (858 males, 1208 females; mean age: 50) from a population based sample. An automated algorithm generated each participant’s WMH distribution, registered onto the MNI-152 standard template. For univariate analysis, each risk factor group was compared to the non-risk factor group. Voxels in which WMH frequency was significantly higher (p<0.05) in the risk factor group were mapped. Multivariate analysis consisted of subgroup analysis to minimize confounding of a risk factor on the others. RESULTS: 431891 MNI-space voxels comprised WMH distribution of the entire population. For univariate analysis, 23697 voxels (5.5%) of these voxels were exclusively associated with hypertension and were prevalent in the anterior frontal lobe. Similarly, 24637 voxels (5.7%) were exclusively associated with diabetes and were prevalent at the callososeptal interface. 7315 voxels (1.7%) were only associated with hypercholesterolemia and did not form a discrete spatial distribution. 282115 voxels (65.3%) were not associated with any of the specified risk factors. Multivariate results corroborated the univariate findings. CONCLUSIONS: Each risk factor was associated with a different spatial distribution of WMH. Hypertension was associated with WMH in the anterior frontal lobe and diabetes was associated with WMH in the callososeptal interface.Item Cardiovascular Risk Indicators and Health-Related Quality of Life in Women Veterans with PTSD(2018-07-26) Anderson, Elizabeth Hallen; Surís, Alina; Fu, Qi; Pai, Anushka; Shivakumar, Geetha; Smith, JuliaPosttraumatic stress disorder (PTSD) is one of the most prevalent disorders among women veterans treated at the Veterans Health Administration and is associated with a wide range of negative physical health outcomes, including the development of cardiovascular disease. In addition, PTSD has a negative impact on an individual's subjective perception of the health-related quality of his or her own life. The majority of studies examining the complex relationship between PTSD and health have utilized primarily male populations. To better understand the impact of PTSD on laboratory-based and self-reported measures of health in women veterans, this study used multivariate analyses of variance to compare cardiovascular risk indicators (resting heart rate, blood pressure, and muscle sympathetic nerve activity) and physical and mental health-related quality of life (SF-36) in a sample of women veterans with PTSD to a sample of nonveteran women without PTSD. In addition, hierarchical multiple regression analyses were used to examine the relationship between PTSD symptom criteria groups and sympathetic nervous system activity indicators and physical and mental health-related quality of life. Results revealed no significant differences between women veterans with PTSD and healthy controls in regards to cardiovascular risk indicators, however women veterans with PTSD reported significantly worse physical and mental health related quality of life. Contrary to expectations, the hyperarousal symptom criteria group was not found to be a significant and unique predictor of sympathetic nervous system activity indicators nor health related quality of life. However, clinician-rated non-hyperarousal PTSD symptom severity was found to be a significant and unique predictor of physical health-related quality of life. Further analysis demonstrated that, of the four PTSD symptom criteria groups, only clinician-rated re-experiencing symptom severity approached being a significant predictor of worse physical health-related quality of life. Since re-experiencing symptoms appear to be an important mechanism by which women veterans make judgments about their physical health, clinically targeting such symptoms in PTSD interventions may result in improved health-related quality of life. Given the relatively young state of research in women veterans with PTSD, it is important to confirm and build on previous research findings for this unique population.Item The cardiovascular risk paradox in polycystic ovarian syndrome(2010-01-15) Chang, Alice Y.Item Central Hemodynamic Monitoring of Train Drivers in Western Russia(2020-01-21) Duncan, Steven G.; Chang, Mary P.; Orlov, Sergei A.; Gorenkov, Roman V.BACKGROUND: Train drivers are exposed to work-related stressors which contribute to higher rates of cardiovascular disease. No studies have characterized precursors of this effect in Western Russia. AIM: This project aims to identify early disturbances and trends in central hemodynamic parameters among young locomotive driver assistants in order to elucidate patterns of decompensation. METHODS: This study is a retrospective review of hemodynamic parameters among train conductors in the Moscow region of the Russian Federation from December 2003 to September 2004. Subjects underwent regular hemodynamic monitoring within this period before every train departure. Automated oscillometric methods were used to obtain resting measurements of blood pressure, cardiac output, pulse wave velocity, and systemic vascular resistance with the device "KAP CG osm – 'Globus'". Men with pre-existing hypertension were excluded. RESULTS: The sample was comprised of 168 individuals and 8674 unique measurements; the mean age was 26.2 ± 4.6 years with an average of 52 ± 17 measurements per person over 33.8 ± 8.9 weeks. The average values for each hemodynamic parameter were within normal limits. Across all measurements, heart rate showed the greatest time-independent variation while systolic blood pressure showed the least; coefficients of variation (σ/x̄) were 10.6% and 6.8% respectively. Hypertensive episodes were observed in 36.3% of participants. Strong, positive correlations were observed between diastolic blood pressure and systemic vascular resistance (r = 0.72, p < 0.001), systolic blood pressure and cardiac output (r = 0.71, p < 0.001) respectively. Older subjects tended to have higher diastolic blood pressure (r = 0.51, p < 0.001). Over time, systemic vascular resistance showed the greatest variance with an average upward trend when data were fit to a linear regression model. Increasing systemic vascular resistance over time was positively correlated with decreasing systolic blood pressure and increasing diastolic blood pressure. DISCUSSION: Persistent changes in central hemodynamics can precede the development of clinical arterial hypertension. The results of this study suggest that implementation of early monitoring and prophylactic measures may be beneficial for high-risk individuals.Item Challenges to the diagnosis and treatment of cardiovascular disease posed by the obesity epidemic(2009-12-04) Das, Sandeep R.Item The choice of therapy for mild hypertension(1981-04-30) Kaplan, Norman M.Item Cholesterol Efflux Capacity: Biological and Clinical Determinants in a Large Multi-Ethnic Population Study (Dallas Heart Study)(2018-01-23) Akinmolayemi, Oludamilola; Rohatgi, AnandBACKGROUND: Cholesterol efflux capacity characterizes the ability of HDL to accept cholesterol from extrahepatic cells in the periphery to the liver, which is a crucial step in reverse cholesterol transport. Cholesterol efflux capacity has been shown in clinical studies to be inversely correlated with prevalent coronary disease and incidence of cardiovascular events, but it is still unclear what biological and clinical determinants drive cholesterol efflux capacity. OBJECTIVES : To determine the biological and clinical variables that associate with cholesterol efflux capacity measured with two different methods in a large multi-ethnic population study (Dallas Heart Study 2) and how these associations differ by sex, race, history of diabetes, and history of cardiovascular disease. METHODS: Cholesterol efflux capacity was measured in the cohort (DHS-2) using both fluorescence (BODIPY) and radiolabeled methods. Statistical analysis was performed using Jonckheere-Terpstra trend test, Mann-Whitney test, and multivariate linear regression. Two-sided p values <0.05 were considered to indicate statistical significance. RESULTS: A total of 2373 participants were included. The median age was 51 years, 57% were women, 51% were black, 5% had history of CVD, and 17% had history of diabetes. Cholesterol efflux capacity measured by radiolabeled method was significantly higher in women than in men (P<0.001). Blacks had the lowest cholesterol efflux capacity measured by both BODIDY (p=0.010) and radiolabeled (p<0.001) methods. Participants without history of CVD had higher cholesterol efflux capacity measured by radiolabeled method compared to those with history of CVD (p=0.048). In multivariate regression, risk factors and circulating markers explained more of the variance in efflux using radiolabel than the variance in efflux using BODIPY (R2 0.195 vs. 0.099) with some overlapping and some distinct markers. Stratification by history of CVD, history of diabetes, race, and sex categories did not alter the findings. CONCLUSION: Our analysis revealed that biological and clinical variables that associate with cholesterol efflux capacity vary with measurement methods, but further studies with different study population validating these differences are needed. An understanding of these differences will be useful in identifying targets to improve cholesterol efflux capacity.Item Complete A-V block(1963-02-14) Bashour, Fouad A.Item The confusing syndromes of cardiovascular autonomic imbalance: cardiovascular dysautonomias(1986-11-06) Mitchell, Jere H.Item Coronary artery calcium: absence makes the heart ... younger?(2017-09-22) Joshi, ParagItem COVID-19 and matters of the heart(2020-04-17) Drazner, Mark