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Browsing by Subject "Heart disease"

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    Analysis of Heart Rate Variability in Male and Female Rats
    (Office of the Vice Chancellor for Research, 2015-04-17) Ajayi, Tolulope O.; Santa Cruz Chavez, Grace; Schild, John H.
    Heart disease is the leading cause of death in the United States. Quantitative measures of cardiovascular function are often essential to effective clinical interventions. The QRS complex is one such measure widely used by cardiologists. These analyses can involve subtle changes in the magnitude and time course of the QRS complex, to differences in the timing between successive heart beats. Electrocardiograms (ECG) are continuous recordings of the QRS complex at various locations across the body surface and provide a comprehensive measurement of the electrical activity of the heart. Knowledge obtained from investigating ECG signal characteristics can help the cardiologist diagnose possible health or cardiac abnormalities such as arrhythmias and can provide objective measures of heart health following injury such as myocardial infarction. Heart rate variability (HRV) can also serve as a reliable indicator of heart health and has been shown to be a strong indicator of mortality and morbidity following myocardial infarction. Unfortunately, very little is known concerning the neurophysiological mechanisms underlying HRV beyond the broader impact of the autonomic nervous system and associated neurocirculatory reflexes. In this research project, we first implemented several established methods for quantifying HRV in male and female rats such as calculating the power spectral density of a long time series of HRV measures, and calculating the standard deviation of the averages of all beat-to-beat intervals in the recording. These measures compared well to those in the literature supporting the accuracy and reliability of the Matlab scripts created to process these data. Simultaneous recordings of the QRS complex and femoral arterial pressure (BP) provided the opportunity to determine how well BP recordings could be used to quantify HRV. In addition, HRV measurements were compared across populations of male and normal, cycling (OVI) and ovariectomized (OVX) female rats in order to determine if HRV is sexually dimorphic. Mentors: John H. Schild, Grace Santa Cruz Chavez, Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUI, Indianapolis, IN
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    Caveolin and oxidative stress in cardiac pathology
    (Frontiers Media, 2025-02-18) Zadorozny, Lauren; Du, Jiayue; Supanekar, Neil; Annamalai, Karthik; Yu, Qing; Wang, Meijing; Surgery, School of Medicine
    Caveolins interact with signaling molecules within caveolae and subcellular membranes. Dysregulation of caveolin function and protein abundance contributes to cardiac pathophysiological processes, driving the development and progression of heart disease. Reactive oxygen species (ROS) play a critical role in maintaining cellular homeostasis and are key contributors to the pathophysiological mechanisms of cardiovascular disorders. Caveolins have been shown to modulate oxidative stress and regulate redox homeostasis. However, the specific roles of caveolins, particularly caveolin-1 and caveolin-3, in regulating ROS production during cardiac pathology remain unclear. This mini-review article highlights the correlation between caveolins and oxidative stress in maintaining cardiovascular health and modulating cardiac diseases, specifically in myocardial ischemia, heart failure, diabetes-induced metabolic cardiomyopathy, and septic cardiomyopathy. A deeper understanding of caveolin-mediated mechanisms may pave the way for innovative therapeutic approaches to treat cardiovascular diseases.
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    Coronavirus is hundreds of times more deadly for people over 60 than people under 40
    (The Conversation US, Inc., 2020-09-10) Menachemi, Nir; Health Policy and Management, Richard M. Fairbanks School of Public Health
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    Daily Situational Brief, February 2, 2015
    (MESH Coalition, 2/2/2015) MESH Coalition
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    Exercise Behavior Is Determined By Pandemic Distress And Task Burden Among Caregivers Of Older Adults
    (Oxford University Press, 2022) Nemati, Donya; Keith, NiCole; Kaushal, Navin; Medicine, School of Medicine
    Background: Caregivers who have dependents with dementia are at a much higher risk of heart disease and mental illnesses compared with non-dementia caregivers. Consequently, these outcomes have been exacerbated by societal barriers that resulted from the pandemic. Engaging in regular physical activity at a moderate-to-vigorous level (MVPA) is beneficial for caregivers has it has been shown to prevent several adverse health outcomes. However, pandemic-related (COVID-19) distress likely worsened caregiver burden which in turn compromised their MVPA levels. The purpose of this study was to understand how caregiving burden impacts MVPA when accounting for physical activity determinants from an augmented Theory of Planned Behavior (TPB) model. Methods: Participants (n=127) were caregivers for older adults (65+) who have dementia. Participants completed measures of MVPA (behavior), TPB, pandemic-related distress (COVID Caregiver Risk Index) and burden scale for family caregivers. The study was investigated using a structural equation model. Results: Participants were 45.5 (SD=3.4) years old, 76.4% female. Attitudes (β=.22, p=.012) and perceived behavioral control (β=.19, p<.001) predicted intention. Attitudes and perceived behavioral control mediated the relationship between past behavior and intention (β=.17, p=.02). Covid distress predicted caregiver burden (β=.35, p<.001), and caregiver burden mediated the effects between distress and behavior (β=-.12, p=.01). Conclusions: Caregiver burden findings suggest that societal changes and demographic-specific burdens related to caregivers need to be considered for caregivers with dependents who have dementia. Taken together, exercise programs that focus on traditional behavioral determinants also need to include specific approaches to buffer caregiving burden experienced in this demographic.
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    A glimpse of Cre-mediated controversies in epicardial signalling
    (Oxford University Press, 2013-12-01) Zhang, Wenjun; Firulli, Anthony B.; Shou, Weinian; Pediatrics, School of Medicine
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    Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication
    (Journal of Rheumatology, 2021) Kurmann, Reto D.; El-Am, Edward A.; Radwan, Yasser A.; Sandhu, Avneek S.; Crowson, Cynthia S.; Matteson, Eric L.; Warrington, Kenneth J.; Mankad, Rekha; Makol, Ashima; Medicine, School of Medicine
    Objective: Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at the time of SSc diagnosis and incidence of VHD during follow-up compared to non-SSc subjects. Methods: Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age and sex to non-SSc subjects. Results: The study included 78 incident SSc cases and 156 non-SSc comparators (56 yrs [± 15.7], 91% female). A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs 0%; P = 0.004) was identified. During follow-up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI 10.7-29.9) in patients with SSc compared with 2.3% (95% CI 0.7-7.0) in non-SSc subjects (HR 4.23, 95% CI 2.03-8.83). Coronary artery disease was the only significant risk factor for VHD. Conclusion: Patients with SSc have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in patients with SSc, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.
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    Molecular Phenotyping and Mechanisms of Myocardial Fibrosis in Advanced Chronic Kidney Disease
    (Wolters Kluwer, 2023) Narayanan, Gayatri; Halim, Arvin; Hu, Alvin; Avin, Keith G.; Lu, Tzongshi; Zehnder, Daniel; Hato, Takashi; Chen, Neal X.; Moe, Sharon M.; Lim, Kenneth; Medicine, School of Medicine
    Key Points: * Myocardial fibrosis in hearts from patients with CKD is characterized by increased trimeric tensile collagen type I and decreased elastic collagen type III compared with hearts from hypertensive or healthy donors, suggesting a unique fibrotic phenotype. * Myocardial fibrosis in CKD is driven by alterations in extracellular matrix proteostasis, including dysregulation of metalloproteinases and cross-linking enzymes. * CKD-associated mineral stressors uniquely induce a fibronectin-independent mechanism of fibrillogenesis characterized by formation of trimeric collagen compared with proinflammatory/fibrotic cytokines. Background: Myocardial fibrosis is a major life-limiting problem in CKD. Despite this, the molecular phenotype and metabolism of collagen fibrillogenesis in fibrotic hearts of patients with advanced CKD have been largely unstudied. Methods: We analyzed explanted human left ventricular (LV) heart tissues in a three-arm cross-sectional cohort study of deceased donor patients on hemodialysis (HD, n=18), hypertension with preserved renal function (HTN, n=8), and healthy controls (CON, n=17), ex vivo. RNA-seq and protein analysis was performed on human donor hearts and cardiac fibroblasts treated with mineral stressors (high phosphate and high calcium). Further mechanistic studies were performed using primary cardiac fibroblasts, in vitro treated with mineral stressors, proinflammatory and profibrotic cytokines. Results: Of the 43 donor participants, there was no difference in age (P > 0.2), sex (P > 0.8), or body mass index (P > 0.1) between the groups. Hearts from the HD group had extensive fibrosis (P < 0.01). All LV tissues expressed only the trimeric form of collagen type I. HD hearts expressed increased collagen type I (P < 0.03), elevated collagen type I:III ratio (P < 0.05), and decreased MMP1 (P < 0.05) and MMP2 (P < 0.05). RNA-seq revealed no significant differential gene expression of extracellular matrix proteins of interest in HD hearts, but there was significant upregulation of LH2, periostin, α-SMA, and TGF-β1 gene expression in mineral stressor–treated cardiac fibroblasts. Both mineral stressors (P < 0.009) and cytokines (P < 0.03) increased collagen type I:III ratio. Mineral stressors induced trimeric collagen type I, but cytokine treatment induced only dimeric collagen type I in cardiac fibroblasts. Mineral stressors downregulated fibronectin (P < 0.03) and MMP2 zymogen (P < 0.01) but did not significantly affect expression of periostin, MMP1, or cross-linking enzymes. TGF-β upregulated fibronectin (P < 0.01) and periostin (P < 0.02) only. Conclusions: Myocardial fibrosis in advanced CKD hearts is characterized by increased trimeric collagen type I and dysregulated collagen metabolism, and is differentially regulated by components of uremia.
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    Multidimensional Mechanistic Spectrum of Long Non-coding RNAs in Heart Development and Disease
    (Frontiers Media, 2021-09-16) Han, Lei; Yang, Lei; Pediatrics, School of Medicine
    With the large-scale genome-wide sequencing, long non-coding RNAs (lncRNAs) have been found to compose of a large portion of the human transcriptome. Recent studies demonstrated the multidimensional functions of lncRNAs in heart development and disease. The subcellular localization of lncRNA is considered as a key factor that determines lncRNA function. Cytosolic lncRNAs mainly regulate mRNA stability, mRNA translation, miRNA processing and function, whereas nuclear lncRNAs epigenetically regulate chromatin remodeling, structure, and gene transcription. In this review, we summarize the molecular mechanisms of cytosolic and nuclear lncRNAs in heart development and disease separately, and emphasize the recent progress to dictate the crosstalk of cytosolic and nuclear lncRNAs in orchestrating the same biological process. Given the low evolutionary conservation of most lncRNAs, deeper understanding of human lncRNA will uncover a new layer of human regulatory mechanism underlying heart development and disease, and benefit the future clinical treatment for human heart disease.
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    Psychological distress in response to physical activity restrictions in patients with non-syndromic thoracic aortic aneurysm/dissection
    (SpringerLink, 2021-10) McEntire, Alexis; Helm, Benjamin M.; Landis, Benjamin J.; Elmore, Lindsey R.; Wilson, Theodore; Wetherill, Leah; Ware, Stephanie M.; Medical and Molecular Genetics, School of Medicine
    Individuals diagnosed with thoracic aortic aneurysm/dissection (TAAD) are given activity restrictions in an attempt to mitigate serious health complications and sudden death. The psychological distress resulting from activity restrictions has been established for other diseases or patient populations; however, individuals with non-syndromic TAAD have not been previously evaluated. Seventy-nine participants completed a questionnaire utilizing the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) questionnaires, which assess levels of depression and anxiety respectively. Additionally, quantitative and qualitative questions explored self-reported psychological distress in response to activity restrictions. Individuals who reported higher PHQ + GAD scores had been living with a diagnosis longer than two years (p = 0.0004), were between 35 and 65 years old (p = 0.05), reported not coping well (p = 0.0035), and reported physical activity was "very important" (p = 0.04). Results from individual questions showed that individuals who reported their diagnosis affected them financially were 3.5 times more likely to report "feeling nervous, anxious, or on edge" (CI = [0.81, 15.6], p = 0.094). Qualitative analysis revealed themes that identified participant beliefs regarding distress, ability to cope, hindrances to coping ability, and resources. These results show psychological distress can result from physical activity restrictions in non-syndromic TAAD individuals. Additionally, certain subpopulations may be more susceptible to distress. This is the first study to examine the psychological distress individuals with non-syndromic TAAD experience as a result of prescribed activity restrictions. Genetic counselors and other healthcare professionals can utilize this information to provide more tailored cardiovascular genetic counseling and increase its therapeutic potential for patients.
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