A5067429117- Cardiovascular Function and Risk Factors
- Cardiovascular Disease and Adiposity
- Cardiovascular Health and Disease Prevention
- Cardiovascular Effects of Exercise
- Cardiomyopathy and Myosin Studies
- Cardiovascular and exercise physiology
- Cardiac Fibrosis and Remodeling
- Cardiac electrophysiology and arrhythmias
- Adipose Tissue and Metabolism
- Heart Rate Variability and Autonomic Control
- Cardiac Imaging and Diagnostics
- Nitric Oxide and Endothelin Effects
- Heart Failure Treatment and Management
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Ischemia and Reperfusion
- Cerebrovascular and Carotid Artery Diseases
- Mitochondrial Function and Pathology
- Cardiac Valve Diseases and Treatments
- Fuel Cells and Related Materials
- Muscle Physiology and Disorders
- Muscle activation and electromyography studies
- Phosphodiesterase function and regulation
- Cardiac pacing and defibrillation studies
- Elasticity and Material Modeling
- Autophagy in Disease and Therapy
Edgewise Therapeutics (United States)
2023-2024
Healthwise
2024
University of Missouri
2014-2023
Missouri College
2012-2023
University of Missouri Health System
2023
University of Missouri System
2018
American College of Cardiology
2018
BG University Hospital Bergmannsheil Bochum
2018
Palo Alto Institute
2018
University of Colorado Boulder
2005-2008
The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile this patient population. This report provides evidence supporting hypothesis Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative cardio-metabolic failure. preclinical model displays a distinctive constellation findings are conceivably useful to extending understanding how pre-existing...
Data regarding the effectiveness of chronic exercise training in improving survival patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine effect on well-defined animal model (HF), using lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present decompensated, dilated between approximately 18 and 23 mo age. SHHF rats were assigned sedentary or exercise-trained groups at 9 16 Exercise consisted 6...
We have previously reported chronic low-intensity interval exercise training attenuates fibrosis, impaired cardiac mitochondrial function, and coronary vascular dysfunction in miniature swine with left ventricular (LV) hypertrophy (Emter CA, Baines CP. Am J Physiol Heart Circ 299: H1348-H1356, 2010; Emter et al. 301: H1687-H1694, 2011). The purpose of this study was to test two hypotheses: 1) preserves normal myocardial oxygen supply/demand balance; 2) training-dependent attenuation LV...
Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects exercise on mortality associated hypertensive disease have not been well defined. In present study, we investigated effect low-intensity progression survival female spontaneously failure rats. Animals severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal or euthanized because age-related...
Cardiac hypertrophy in response to hypertension or myocardial infarction is a pathological indicator associated with heart failure (HF). A central component of the remodeling process loss cardiomyocytes via cell death pathways regulated by mitochondrion. Recent evidence has indicated that exercise training can attenuate reverse remodeling, creating physiological phenotype. The purpose this study was examine left ventricular (LV) function, and cardiomyocyte mitochondrial function...
Population studies have shown that compared to diabetic men, women are at a higher risk of cardiovascular disease. However, the mechanisms underlying this gender disparity unclear. Our in young murine models type 2 diabetes mellitus (T2DM) and disease show male rats develop increased cardiac fibrosis suppression intracardiac anti-fibrotic cytokines, while premenopausal female do not. This protection from can be an estrogen-related effect. early subclinical myocardial deformation, hypertrophy...
Impaired microvascular insulin signaling may develop before overt indices of endothelial dysfunction and represent an early pathological feature adolescent obesity. Using a translational porcine model juvenile obesity, we tested the hypotheses that in stages obesity development, impaired manifests skeletal muscle (triceps), brain (prefrontal cortex), corresponding vasculatures, depressed insulin-induced vasodilation is reversible with acute inhibition protein kinase Cβ (PKCβ). Juvenile...
Background Cyclic guanosine monophosphate‐protein kinase G‐phosphodiesterase 5 signaling may be disturbed in heart failure ( HF ) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was manipulate cyclic monophosphate using the dipeptidyl‐peptidase 4 inhibitor saxagliptin phosphodiesterase tadalafil. We hypothesized that preservation cGMP would attenuate pathological improve left ventricular LV function. Methods Results assessed...
Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role development HF; therefore, purpose this study was to assess effects low-intensity interval on coronary function sedentary (HF) trained (HF-TR) aortic-banded miniature swine displaying LV...
Concentric and eccentric cardiac hypertrophy are associated with pressure volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms characterized by asymmetrical growth the myocyte mainly width or length, respectively. The molecular mechanisms determining preferential versus length remain poorly understood. Identification governing could provide new therapeutic targets for prevention treatment
To investigate the use of cine multidetector computed tomography (CT) to detect changes in myocardial function a swine cardiomyopathy model.All animal protocols were accordance with Principles for Utilization and Care Vertebrate Animals Used Testing Research Training approved by University Missouri Animal Use Committee. Strain analysis CT images left ventricle was optimized analyzed feature-tracking software. The standard reference strain harmonic phase tagged cardiac magnetic resonance (MR)...
We recently developed a clinically relevant mini-swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated increased mitochondrial permeability transition (MPT). Early function is ATP and Ca2+-dependent, thus, we hypothesized chronic low doses cyclosporine (CsA) would preserve via inhibition MPT subsequently maintain normal cardiomyocyte Ca2+ handling contractile characteristics. Left ventricular cardiomyocytes were isolated from...
This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism and treatment a physical activity intervention restores vasoreactivity to insulin through augmented nitric oxide synthase (NOS)-dependent dilation. Otsuka Long-Evans Tokushima Fatty rats were divided into following groups: 20 wk old food controlled (CON-20); free access (model of obesity, OB-20); 40 (CON-40);...
Key points It has been postulated that increased blood flow‐associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin‐stimulated vasodilatation. This report provides evidence supporting the hypothesis exerts insulin‐sensitizing effects in vasculature and this based experiments vitro cells, ex vivo isolated arterioles humans. Given recognition vascular insulin signalling, associated enhanced microvascular perfusion, contributes to...
Heart failure arises, in part, from a constellation of changes cardiac myocytes including remodeling, energetics, Ca
Postmenopausal women represent the largest cohort of patients with heart failure preserved ejection fraction, and vascular dementia represents most common form in fraction. Therefore, we tested hypotheses that combination cardiac pressure overload (aortic banding [AB]) loss female sex hormones (ovariectomy [OVX]) impairs cerebrovascular control spatial memory.Female Yucatan miniswine were separated into 4 groups (n=7 per group): (1) control, (2) AB, (3) OVX, (4) AB-OVX. Pigs underwent OVX AB...
Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) advanced glycation end products (AGE) both promote arterial stiffness, yet mechanisms by which PVAT promotes efficacy exercise to prevent are unknown. We hypothesized that chronic continuous interval training would PVAT-mediated AGE secretion stiffness. Yucatan miniature swine were divided into four groups:...
Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), manifests with blunting insulin-induced vasodilation. Although there is evidence that females are more whole body sensitive than males in the healthy state, whether sex differences exist vascular sensitivity unclear. Also uncertain weight loss can reestablish T2D. The purpose this investigation was to 1) establish if vasodilatory responses absence disease, 2) determine female affords protection against...
Background Cognitive impairment in the setting of heart failure with preserved ejection fraction remains poorly understood. Using aortic‐banded miniature swine displaying pathological features human fraction, we tested hypothesis that increased carotid artery stiffness and altered blood flow control are associated impaired memory independent decreased cardiac output. Furthermore, hypothesized chronic exercise prevents vascular restructuring preserves normal cognition fraction. Methods...
Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling the cardiomyocyte considered important for development heart failure. Under control a cardiomyocyte-specific promoter, AAV9sc.shmAKAP AAV9sc.RBD express small hairpin RNA perinuclear scaffold protein muscle A-kinase anchoring β (mAKAPβ) an...
Exercise improves clinical outcomes in patients diagnosed with heart failure reduced ejection fraction (HFrEF), part via beneficial effects on cardiomyocyte Ca2+ cycling during excitation-contraction coupling (ECC). However, limited data exist regarding the of exercise training function preserved (HFpEF). The purpose this study was to investigate handling and contractile following chronic low-intensity aortic-banded miniature swine test hypothesis that a large animal model pressure overload....
Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, purpose this study was determine therapeutic efficacy chronic interval exercise training (IT) on large-conductance Ca2+-activated K+ (BKCa) channel-mediated coronary vascular function in failure. We hypothesized that would attenuate pressure overload-induced impairments BKCa function. A translational large-animal model cardiac features HFpEF used test...