Master of Science in Environmental Science, Youngstown State University, 2016, Department of Physics, Astronomy, Geology and Environmental Sciences

This study investigates the possible correlation between ischemic heart disease and magnesium concentrations in Ohio drinking water using linear regression analysis. Three correlation analyses were made in this study: (1) magnesium concentrations vs. heart disease rates, (2) magnesium concentrations vs. heart disease mortality rates, and (3) magnesium concentrations vs. heart disease mortality rates in people age 35 and above. Magnesium concentrations in drinking water were obtained from 69 of the 88 Ohio counties. The magnesium concentrations vary from 10 to 70 mg/l. To investigate the effects of the different magnesium concentration levels on heart disease and mortality, the concentrations were divided into four groups: 10-19 mg/l, 20-29 mg/l, 30-39 mg/l, and greater than 40 mg/l. In correlations (1) and (3), linear regression was applied to each magnesium concentration group and to all four groups combined as one group. In correlation (2), linear regression was applied to the four magnesium groups. Microsoft Excel was used to run the regression analysis. Results of the three correlations yielded a negative correlation between ischemic heart disease (rates and mortality) and magnesium concentrations in drinking water. This supports the hypothesis that magnesium may help to protect against death from heart disease. The three correlations yielded low correlation coefficients ranging from 0.33 to 0.50, indicating that factors other than magnesium concentrations may affect heart disease rates and mortality (e.g., high blood pressure, high cholesterol, genetic factors, etc.). The highest magnesium concentrations in Ohio drinking water are found in the northwestern part of the state where dolomite outcrops are present.

Committee: Isam Amin PhD (Advisor); Alan Jacobs PhD (Committee Member); Colleen McLean PhD (Committee Member); Larry Gurlea (Committee Member) Subjects: Health

Master of Science in Environmental Science, Youngstown State University, 2012, Department of Physics, Astronomy, Geology and Environmental Sciences

This study investigates the possible correlation between heart disease mortality and the hardness of drinking water to determine if there are protective factors associated with hard water that may reduce heart disease. The study attempts to see if such a correlation can be found in the population that is supplied by 31 public water treatment plants spread across 17 counties in Ohio. The 31 public water treatment plants, which maintain a hardness with little variance from year to year, serve an estimated total 2,658,000 customers, about 25% of the total population of Ohio. Surface-water supplies 69% of the population, groundwater 30% and 1% is supplied by a mixture of surface-water and groundwater. The total hardness, expressed in mg/l CaCO3 , of the study area ranges from an annual average of 93 mg/l to 448 mg/l. To test for a correlation, total hardness data is acquired on the drinking water supplied by the water treatment plants and is compared to heart disease mortality data, for the year 2007, obtained from the Ohio Department of Health, Center for Public Health Statistics and Information. Analysis shows that a positive correlation of 0.427 exists, with changes in total water hardness accounting for 18.3% of the variance found in heart disease mortality rate. An age adjusted analysis, for individuals over 35 years of age also resulted in a positive correlation with total water hardness accounting for 15.4% of the variance in heart disease mortality. In order to eliminate possible confounding factors from the study, 16 additional examinations were done on the original data; all but three resulted in positive correlations.

Committee: Isam Amin Ph.D. (Advisor); Harry Bircher (Committee Member); Hans Tritico Ph.D (Committee Member); Alan Jacobs Ph.D. (Committee Member) Subjects: Environmental Health; Environmental Science

MS, University of Cincinnati, 2016, Medicine: Clinical and Translational Research

Objectives: Diastolic dysfunction (DD), a key driver of long-term Fontan outcomes, may be concealed during standard hemodynamic evaluation. We sought to identify Fontan patients with occult DD using “ventricular stress testing” with rapid volume expansion (RVE). Methods: Cardiac catheterization with RVE was performed routinely in Fontan patients between 11/2012 and 4/2015. Baseline and post-stress hemodynamic data were compared using t-test, Mann-Whitney U test, X2 and Fisher's exact tests. A post-stress ventricular end diastolic pressure (EDP) threshold of 15 mmHg defined occult DD. Results: Forty-six Fontan patients (48% female, median age 14.1 (IQR 9.1,21.3) years) were included. The median Fontan duration was 10.8 (IQR 5.1,17.8) years and dominant left ventricular morphology was present in 63% of patients. Volume expansion increased mean Fontan pressure (15.2±2.5 vs. 12.4±2.2 mmHg, p<0.001), pulmonary capillary wedge pressure (11.3±2.6 vs. 7.9±2 mmHg, p<0.001) and EDP (12.7±3.3 vs 8.5±2.1 mmHg, p<0.001). Sixteen patients (35%) had occult DD, demonstrating higher baseline EDP (10.3±1.9 vs. 7.6±1.5 mmHg, p<0.001) and greater increase in EDP (6.3±2.4 vs. 3.1±1.4 mmHg, p<0.001) compared to patients without DD. Higher baseline EDP, lower baseline cardiac index and longer duration of Fontan circulation were associated with higher post-stress EDP. There were no complications related to RVE. Conclusion: Ventricular stress testing by RVE is feasible, safe and identifies a subgroup of Fontan patients with occult DD. Higher baseline EDP and longer duration of Fontan circulation are associated with worse diastolic function. Future work is necessary to better understand the etiology, associations and clinical implications of occult DD in Fontan survivors.

Committee: Erin Nicole Haynes Dr.P.H. (Committee Chair); Michael David Seckeler M.D. M.Sc. (Committee Member); Bryan Howard Goldstein M.D. (Committee Member) Subjects: Surgery

DNP, Otterbein University, 2015, Nursing

Abstract Filipino-Americans (FAs) are considered the fastest growing Asian immigrant population in the United States. There are about 2.6 million Filipino-Americans living in the United States (U.S. Census, 2010). Coronary Heart Disease (CHD) is the leading cause of death among FAs in the United States (National Vital Statistics, 2009). Research studies on CHD and CHD risk factors among FAs are limited. The purpose of the study was to explore FA's knowledge of CHD, risk factors for CHD and to provide a personalized educational intervention in raising awareness and changing attitudes about CHD among FAs aged 35-75 in a community setting in Woodside, New York. Knowledge about CHD and its risk factors are vital components in engaging FAs to a healthier lifestyle. A quantitative study with a descriptive design was used in the study to explore CHD knowledge and CHD risk factors among FAs in a community setting. The Heart Disease Facts Questionnaire (Wagner, Lacey, Chyun, & Abbott, 2005), Socio-demographic and Cardiac Risk profile was used to obtain the data for the study. Data was gathered and obtained from September 2014 to December 2014 in a convenience sample of thirty seven participants. Simple descriptive statistics, such as mean, standard deviation and percentages, were used to analyze the data in the study. A personalized education program was provided to the participants based on their CHD knowledge and cardiac risk profile. The participants had suboptimal scores on the HDFQ questionnaire and the participants had some significant risk factors for CHD. The study revealed that the majority of the participants' attitudes or feelings about making lifestyle changes related to the prevention of CHD changed after their personalized education intervention. Despite the limitations in the study, data gathered in the study is a step toward developing evidence-based prevention and health promotion interventions to reduce the risk of coronary heart disease amon (open full item for complete abstract)

Committee: Patricia Keane (Committee Chair); John Chovan (Committee Member); David Rubenstein (Committee Member); Domingo Susan (Committee Member) Subjects: Health Education; Health Sciences, Public Health; Nursing

Master of Science, The Ohio State University, 1969, Graduate School

Committee: Not Provided (Other) Subjects:

MA, Kent State University, 2024, College of Arts and Sciences / Department of Psychological Sciences

Heart disease (HD) remains the leading cause of death (LCOD) in America. Despite public health campaigns, awareness of this fact decreased from 65% in 2009 to 44% in 2019 among women over the age of 25 and was only 10% for women aged 15-24. Declines were greater for women younger than 65, Hispanic, and Black. In 2021, the National Heart, Lung, and Blood Institute (NHLBI) issued a notice of special interest in promoting cardiovascular health earlier in life. The current cross-sectional study compared awareness of HD as the leading cause of death (LCOD) and greatest health problem among Black and White women and men aged 20-39. Given that Black women have a higher risk of HD than White women, we were particularly interested in possible race and sex differences in HD awareness among young adults. We hypothesized that women would be less aware that heart disease is the LCOD and the greatest health problem for people of all ages. We also expected Black women would be less likely to identify heart disease as the LCOD and the greatest health problem and would report lower levels of motivation to improve their CVH and reduce their risk for CVD compared to young White women. The online survey was conducted using QualtricsXM panels. Respondents (n = 404) included Black women (25.0%, 29.0 ± 6.1 yrs), White women (24.3%, 26.4 ± 4.3 yrs), Black men (24.8%, 30.6 ± 5.2 yrs), and White men (25.9%, 32.8 ± 4.5 yrs). Correct identification of HD as the LCOD was similar for women and men whether choosing from a list (24.1% vs. 26.8%) or by ranking the top 5 LCODs (17.6% vs. 20.0%) [χ2(1, 404), p ≥ .53]. Whereas 31.7% of males correctly identified HD as the LCOD for people whose birth sex is male, only 15.6% of females correctly identified HD as the LCOD death in people whose birth sex is female [χ2(1, 404) = 14.5, p < .001]. Likewise, only 13.6% of females correctly identified HD as the greatest health problem for people whose birth sex is female, compared to 29.3% of males that cor (open full item for complete abstract)

Committee: Joel Hughes (Advisor) Subjects: Psychology; Public Health; Sociology

MS, University of Cincinnati, 2020, Medicine: Clinical and Translational Research

Background: As life expectancy for adolescents and young adults (AYA) with chronic conditions continues to increase, there is a critical need to understand how the growing prevalence of this population as they age affects use of pediatric compared to adult hospitals. Objective: To determine 1) how pediatric hospital use changes by age for AYA with congenital heart disease (CHD), cystic fibrosis (CF), and sickle cell disease (SCD), and 2) if specific chronic condition is associated with delayed inpatient transition for AYA aged 22-35 years (as defined by admission to a pediatric hospital). Methods: We conducted a cross-sectional analysis of admissions for AYA ages 12-35 years with CHD, CF, and SCD in the 2016 National Inpatient Sample (NIS). Individuals with CHD, CF, and SCD were identified by ICD-10-CM diagnosis codes. We measured the percentage of all admissions occurring at pediatric hospitals compared with non-pediatric hospitals at each age in years for each chronic condition. To determine if chronic condition was associated with delayed inpatient transition for AYA aged 22-35 years, we used multivariable logistic regression. Results: We identified 124,475 annual admissions of AYA ages 12-35 years with CHD, CF, and SCD of which 13,380 were to pediatric hospitals. Use of pediatric hospitals decreased as age increased for all three conditions. For AYA ages 22-35, the average percent of hospitalizations at a pediatric hospital was 3.4% for CF, 2.6% for CHD, and 0.2% for SCD. AYA ages 22-35 with CF and CHD were associated with significantly higher odds of admission to a pediatric hospital compared to those with SCD. Conclusion: Older AYA with CHD and CF are more likely to be admitted to pediatric hospitals compared to AYA with SCD. Pediatric hospitals admit few AYA > 21 years with these three common chronic conditions affecting the entire lifespan.

Committee: Aimin Chen Ph.D. (Committee Chair); Katherine Auger (Committee Member); Yingying Xu PhD MA MS BE (Committee Member) Subjects: Surgery

Doctor of Philosophy, The Ohio State University, 2017, Psychology

Individuals endorsing higher rates of delay discounting (DD) tend to discount the value of future rewards, such that the perceived value of the future reward, though larger than an immediate reward, is viewed as less valuable. In turn, DD is associated with engaging in poor health behaviors, such as unhealthy diet and low levels of physical activity, both of which may increase risk of developing cardiovascular disease (CVD). Individuals with elevated genetic risk for CVD and higher rates of DD, are likely to be especially vulnerable to developing CVD. This randomized controlled study examined rates of DD among young adults with a family history (FH) of early-onset CVD (i.e., adults with higher genetic risk for CVD; FH+) and without a FH of CVD (FH-). Associations of DD, perceived CVD risk, physical activity, dietary sodium and lipid intake, as well as health behavior intentions were assessed before, immediately following, and one week after a standard educational intervention. In addition, FH was evaluated as a moderator of these associations. High rates of DD were hypothesized to correlate with sodium and lipid consumption, and negatively correlate with perceived risk of developing CVD, level of physical activity, and intention to engage in healthy behaviors. Further, it was hypothesized that FH+ participants randomized to the experimental condition would report greater reductions in DD, sodium and lipid intake, and increases in physical activity, perceived disease risk, and health behavior intentions, compared to FH- participants in the experimental condition, and participants in the control condition. Fifty-four FH+ and 60 FH- adults between the ages of 18 and 40, with no personal history of CVD were randomized to view either an educational video about CVD, or a control educational video. Questionnaires assessed perceived risk of developing CVD, intention to engage in health behaviors, lipid and sodium intake, as well as physical activity. DD was assessed with (open full item for complete abstract)

Committee: Charles Emery PhD (Advisor); Melissa Buelow PhD (Committee Member); Julian Thayer PhD (Committee Member) Subjects: Psychology

Doctor of Philosophy, The Ohio State University, 2017, Molecular Genetics

Congenital heart disease (CHD) is the most common birth defect and affects around 2% of live births, when including bicuspid aortic valve (BAV). Although surgical care has significantly improved patient outcome, it remains a major contributor to morbidity and mortality. Population and family based studies have identified a strong genetic component to CHD, however the exact etiology by which CHD occurs is not well understood. Clinically, there is a lack of genetic diagnostic tools available for these patients. While whole exome and whole genome sequencing offer potential benefits to this patient population, it has not yet been utilized or tested in a clinical setting. Additionally, pipelines have not yet been developed to systematically analyze the large sequencing datasets that these approaches produce. As genomic testing continues to become more accessible to clinicians and patients, it is crucial that pipelines are developed that allow for a streamlined clinical testing approach. We propose the utilization of whole exome sequencing, with a candidate gene prioritization approach, to allow for the identification of causative mutations in familial CHD. We performed whole exome sequencing on 9 families with Mendelian inherited CHD and prioritized the variants utilizing a CHD gene list and further filtered based on segregation, rarity, and predicted pathogenicity. This approach was successful in the identification of potentially pathogenic variants in 3 of the 9 families, and included mutations in GATA4, TLL1, and MYH11. This work supports the use of clinical whole exome sequencing in familial cases of CHD, and offers a pipeline for a streamlined approach to identify high-quality, disease causing mutations. Identifying disease associated variants is the first step toward understanding the underlying role of genetics in CHD. However, to determine causality and to determine mechanism one must utilize a model system, allowing for the manipulation of the gene of int (open full item for complete abstract)

Committee: Vidu Garg MD (Advisor); Susan Cole PhD (Committee Member); Joy Lincoln PhD (Committee Member); Helen Chamberlin PhD (Committee Member); Harald Vassein PhD (Committee Member) Subjects: Genetics; Molecular Biology

Doctor of Philosophy, The Ohio State University, 2016, Biomedical Engineering

Endothelial cells (ECs) line the inside of blood vessels and are constantly exposed to fluid mechanical forces from the flow of blood over their surface and the motion of the vessel wall. These forces, under physiological conditions, are transduced into intracellular signals that maintain vascular health and reduce the risk of cardiovascular disease. An extremely important signal in response to shear stress is in the form of intracellular calcium concentration ([Ca2+]i) oscillations. Ca2+ is a ubiquitous second messenger and is involved in a large number of intracellular signaling cascades including those that regulate nitric oxide production (a potent vasodilator that plays a significant role in maintaining vascular health). In addition, mitochondrial Ca2+ overload leads to cell apoptosis (programmed cell death) due to the release of cytochrome c from the inner mitochondrial membrane which activates a series of caspases that leads to cell death. Ca2+ may enter the EC across the plasma membrane, or it may be released from the intracellular stores (the endoplasmic reticulum (ER) and the mitochondria). The [Ca2+]i is approximately 10-100 nM under basal conditions, while the extracellular [Ca2+] is about 2 mM. This creates a strong driving force for Ca2+ transport across the plasma membrane into the cytosol. Inside the cell, the ER contains ~75% of the intracellular Ca2+ and has one major efflux mechanism, the inositol 1,4,5 trisphosphate receptor (IP3R) and one major Ca2+ influx pathway, the sarco/endoplasmic reticulum ATP-ase (SERCA). The mitochondria sequester the majority of the remaining 25% of intracellular Ca2+ and have one major Ca2+ influx mechanism, the mitochondrial Ca2+ uniporter (MCU), and one major Ca2+ efflux pathway, the mitochondrial sodium (Na+)/Ca2+ exchanger (mNCX). Despite the significance of [Ca2+]i in maintaining EC and vascular health, the mechanisms modulating the shear-induced [Ca2+]i signal had yet to be determined. By using the Ca2+-sens (open full item for complete abstract)

Committee: B. Rita Alevriadou PhD (Advisor); Thomas Hund PhD (Committee Member); Jay Zweier MD (Committee Member) Subjects: Biomedical Engineering

Master of Science, The Ohio State University, 2015, Kinesiology

Tools for the functional assessment of cardiovascular fitness are needed to establish animal models of dysfunction and the effects of novel therapeutics. Currently, exercise assays are widely published; however, they have limited sensitivity for assessing the cardio-metabolic phenotype of mice. In human research, the graded maximal exercise test (GXT) is a gold standard diagnostic for measuring cardiovascular function. Present published testing methods in mice use set inclination and progressive increases in speed until exhaustion (PXT); thus lacking characteristics of the GXT. We developed a GXT test that allows for assessment of cardiovascular fitness in metabolic and genetic models of cardiovascular dysfunction; as well as in healthy mice. The results of comparison between this method and the PXT revealed that only the GXT test provides sensitive, quantitative, parameters for diagnosing and monitoring cardiovascular, metabolic and pulmonary function in mouse models.

Committee: Ouliana Ziouzenkova Dr. (Advisor); Brian Focht Dr. (Advisor); Denis Guttridge Dr. (Committee Member) Subjects: Kinesiology

MA, Kent State University, 2011, College of Arts and Sciences / Department of Psychological Sciences

Increased sleep impairment is a common symptom of cardiovascular disease, and can contribute to difficulty with normal activities of living. One explanation for the increased sleep impairment observed in persons with cardiovascular disease is the presence of chronic, low-level inflammation. Cytokines are neuroimmunomodulating cells that can signal various physiological processes, such as sleep. Cytokines are secreted in abundance by immune cells as well as epithelial cells, and are thought to be secreted in low-levels in people with cardiovascular disease, thus leading to sustained inflammation. This study investigated the association between cytokine levels as well as t-helper type 1 (Th1) to t-helper type 2 (Th2) ratio and factors of sleep in patients who were diagnosed with cardiovascular disease. Ninety-six participants recruited from a cardiovascular rehabilitation program were asked to complete the Pittsburgh Quality Sleep Index (PSQI) and to undergo a venous blood draw within the first two weeks of rehabilitation. Analysis of Covariance (ANCOVA) revealed that participants who reported an inability to get to sleep within 30 minutes had higher blood plasma concentrations of IL-10 (M = 1.52, SD = 0.54 versus M = 1.24, SD = 0.46, F (1,69) = 4.48, p = .038) and TNF-α (M = 2.14, SD = .61 versus M = 1.78, SD = .71, F (1, 69) = 4.70, p = .034). In addition, TNF-α to IL-4 ratio in blood plasma was increased in participants reporting an inability to fall asleep within 30 minutes when compared to participants who reported that they fell asleep within 30 minutes (M = 1.40, SD = .572 versus M = 1.16, SD = .555, F (1, 63) = 5.81, p = .019). Multiple regression analysis revealed that IFN-γ was positively correlated with sleep duration (B = .466, p = .038). In conclusion, this study provides evidence that sleep impairment may be a result of chronic inflammation in patients with heart disease. Future research is indicated to understand the causal relationship between sleep an (open full item for complete abstract)

Committee: Joel Hughes PhD (Advisor); John Gunstad PhD (Committee Member); David Riccio PhD (Committee Member); Kathryn Kerms PhD (Committee Member) Subjects: Psychobiology

Doctor of Philosophy, Case Western Reserve University, 2011, Nursing

The purpose of this study was to explore the themes that affected the day-to-day health-related decision making of African Americans managing coronary heart disease (CHD). Understanding the lived experience of African Americans with CHD can offer health care providers additional strategies to improve disease management. A hermeneutic phenomenological approach was utilized to explore: 1) what is the lived experience of managing CHD among older African Americans? 2) What is the essence of health-related decision making among older African Americans living with CHD? Two audio taped 30 to 60 minute open ended in-depth interviews per participant. Purposive sampling resulted in eight African Americans male = 4; female = 4 over age 45 admitted with acute coronary syndrome (ACS) to a large metropolitan hospital. Bracketing and phenomenological reduction elicited units of general meaning and allowed openness of the themes that emerged. The results of this study indicate that the lived experience of African Americans with newly diagnosed CHD respond similar to other racial/ethnic groups. In this study a new functional limitation was almost certain for older African Americans recovering from an ACS. Physical limitations led to feelings of loss of freedom, loss of control, and symptoms of depression. African Americans seem to have a different manifestation of depressive symptoms. Females were more likely to lack sources of support. Although the practice environment was not the focus of this study, it is important to note that national guidelines for reducing health disparities related to CHD had been implemented in the clinical setting. The data support the idea that culture is influential in health-related decision making. More importantly, the African Americans in this small sample demonstrated self-management skills and viewed their provider as partners in disease management. The majority of participants had established primary care providers whom they visited regularly. Par (open full item for complete abstract)

Committee: Diana Morris (Committee Chair); Cheryl Killion (Committee Member); Patricia Higgins (Committee Member); Marco Costa (Committee Member) Subjects: African American Studies; African Americans; Behavioral Psychology; Behavioral Sciences; Black Studies; Ethnic Studies; Health Care; Health Sciences; Nursing; Public Health; Social Research

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

This dissertation explores the role of long non-coding RNAs in congenital heart disease (CHD), the most common birth defect worldwide, where many genetic contributors remain unknown. We investigate lncRNAs in two key areas: copy number variants (CNVs) and single nucleotide variants (SNVs), aiming to identify novel lncRNA candidates and develop new tools for predicting their pathogenicity. While CNVs are known to contribute to CHD, the involvement of lncRNAs within these regions has been largely unexplored. Additionally, no existing computational tools specifically assess the pathogenic potential of heart-specific lncRNA variants, presenting a critical gap in CHD research. The first study focuses on identifying lncRNAs within CNVs that are linked to CHD. By combining CNV data with transcriptomic information from human heart development, we discover lncRNA candidates that may play significant regulatory roles in heart formation. This study provides a reproducible platform for investigating lncRNAs in the context of CNVs, advancing our understanding of their contributions to CHD. The second study introduces HeartiLNC, a novel machine learning-based score designed to predict the pathogenicity of SNVs in lncRNAs. This tool integrates heart- specific lncRNA expression profiles, population frequency data, and RNA secondary structure analysis. HeartiLNC offers a unique approach to identifying potentially deleterious variants that may contribute to CHD. This method represents a significant advancement in computational genomics, offering new insights into the genetic regulation of heart development. Together, these studies contribute to the understanding of lncRNAs in CHD, providing new tools for genetic analysis. This work highlights the importance of investigating both CNVs and SNVs in the non-coding genome to uncover the complex genetic architecture underlying CHD. We hope that one day these findings will lead to improvement in CHD diagnosis (open full item for complete abstract)

Committee: Peter White (Advisor); Kim McBride (Advisor); Michelle Wedemeyer (Committee Member); Ralf Bundschuh (Committee Member); Dawn Chandler (Committee Member) Subjects: Bioinformatics; Biomedical Research

Master of Science, The Ohio State University, 1970, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1970, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2008, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1967, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1966, Graduate School

Committee: Not Provided (Other) Subjects:

PhD, University of Cincinnati, 2024, Medicine: Cancer and Cell Biology

Congenital heart disease (CHD) stands as the most prevalent congenital anomaly, impacting approximately 4 per 1000 live births. Single ventricle (SV) CHD, constituting 7.7% of CHDs, represents a severe and intricate form of CHD where patients typically exhibit a single dominant left or right ventricle at birth, insufficient to sustain normal pulmonary and systemic circulation. SV CHDs encompass diverse cardiac malformations, including semilunar (SL) or atrioventricular (AV) valve hypoplasia, stenosis/atresia, and malalignment of the pulmonary artery and aorta. The varied manifestations of SV abnormalities imply a complex disease etiology intertwined with various cardiac developmental anomalies. Despite substantial progress in understanding the molecular mechanisms of various SV diseases, intrinsic defects in human cardiac endothelium and related valvular structures remain elusive. The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized our ability to precisely dissect cellular identity, functions, and interactions during cardiogenesis and CHD pathogenesis. Leveraging human induced pluripotent stem cells (iPSCs) expands our experimental repertoire, allowing the generation of various cardiac cell types to functionally validate genomic and transcriptomic data in cellular models. Herein, we combined scRNA-seq analysis of human tissues with patient-derived iPSCs to unravel the endothelial/valvular pathobiology in SV diseases, such as hypoplastic left heart syndrome (HLHS) and pulmonary stenosis (PS). The effort extended to specify iPSC-derived valve endothelial cells (VECs) and valve interstitial cells (VICs) representing the specificity of all four valves. Despite the previous knowledge of myocardial defects in HLHS pathology, we demonstrated the intrinsic defect in disease vascular arterial endothelium, including KMT2D-NOTCH mediated proliferation, angiogenesis, and EC-smooth muscle cell interactions. Our results suggested the importance o (open full item for complete abstract)

Committee: Mingxia Gu M.D. Ph.D. (Committee Chair); Susanne Wells Ph.D. (Committee Member); Mei Xin Ph.D. (Committee Member); Katherine Yutzey Ph.D. (Committee Member); Yanbo Fan Ph.D. (Committee Member) Subjects: Biology