A5031818852- Cardiac Ischemia and Reperfusion
- Cardiomyopathy and Myosin Studies
- Protein Tyrosine Phosphatases
- Cardiovascular Function and Risk Factors
- Galectins and Cancer Biology
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Cardiac Fibrosis and Remodeling
- Peptidase Inhibition and Analysis
- Cardiac Arrest and Resuscitation
- Cardiac Structural Anomalies and Repair
- Signaling Pathways in Disease
- Fuel Cells and Related Materials
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Connective tissue disorders research
- Receptor Mechanisms and Signaling
- Congenital heart defects research
- PI3K/AKT/mTOR signaling in cancer
- Organ Transplantation Techniques and Outcomes
- Metabolism, Diabetes, and Cancer
- Protease and Inhibitor Mechanisms
- Alcohol Consumption and Health Effects
University of Missouri
2015-2025
Cardiovascular Research Center
2023
University of Missouri Hospital
2018
Cincinnati Children's Hospital Medical Center
2001-2009
University of Cincinnati
2002-2007
University of South Alabama
2001-2002
University of Münster
2001
Heinrich Heine University Düsseldorf
2000
University of Freiburg
1994
Following myocardial infarction, nonischemic myocyte death results in infarct expansion, loss, and ventricular dysfunction. Here, we demonstrate that a specific proapoptotic gene, Bnip3, minimizes remodeling the mouse, despite having no effect on early or late size. We evaluated effects of ablating Bnip3 cardiomyocyte death, size, after surgical ischemia/reperfusion (IR) injury mice. Immediately following IR, significant differences were observed between Bnip3–/– WT However, at 2 days...
Functional cell-free systems may be excellent tools with which to investigate light-dependent signal transduction mechanisms in plants. By evacuolation of parsley protoplasts and subsequent silicon oil gradient centrifugation lysed evacuolated protoplasts, we obtained a highly pure concentrated plasma membrane-containing cytosol. Using GT- G-box DNA elements, were able demonstrate specific localization pool binding activity factors (GBFs) but not one GT-box this cytosolic fraction. The the...
Noonan syndrome (NS) is an autosomal dominant disorder characterized by a wide spectrum of defects, which most frequently include proportionate short stature, craniofacial anomalies, and congenital heart disease (CHD). NS the common nonchromosomal cause CHD, 80%-90% patients have cardiac involvement. Mutations within protein tyrosine phosphatase Src homology region 2, 2 (SHP2) are responsible for approximately 50% cases with To understand developmental stage- cell type-specific consequences...
Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis adverse cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced fibroblast proliferation migration are NADPH oxidase (Nox) 4/ROS IL-18 dependent. Our results show that the potent induction of mouse (CF) by Ang-II is markedly attenuated Nox4 knockdown Nox inhibitor DPI. Further, DPI pre-treatment Ang-II-induced IL-18, IL-18Rα collagen expression, MMP9 LOX activation....
Abstract Aims Cardiomyocyte Ca2+ homeostasis is altered with aging via poorly-understood mechanisms. The Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel an osmotically-activated channel, and there limited information on the role of TRPV4 in cardiomyocytes. Our data show that protein expression increases cardiomyocytes aged heart. objective this study was to examine cardiomyocyte following hypoosmotic stress assess contribution cardiac contractility tissue damage...
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...
Two myosin isoforms are expressed in myocardium, αα-homodimers (V 1 ) and ββ-homodimers 3 ). V exhibits higher velocities myofibrillar ATPase activities compared with . We also observed this for cardiac from normal propylthiouracil-treated mice. Actin velocity a motility assay ( actin over was twice that of as the ATPase. Myosin's average force (F avg similar Comparing F across species both , our laboratory showed previously (VanBuren P, Harris DE, Alpert NR, Warshaw DM. Circ Res 77:...
Comparison of mammalian cardiac α- and औ-myosin heavy chain isoforms reveals 937 identity. To date, genetic methodologies have effected only minor switches in the myosin isoforms. Using cardiac-specific transgenesis, we now obtained major isoform shifts and/or replacements. Clusters non-identical amino acids are found functionally important regions, i.e. surface loops 1 2, suggesting that these structures may regulate isoform-specific characteristics. Loop alters filament sliding velocity,...
Noonan syndrome (NS) is the most common nonchromosomal genetic disorder associated with cardiovascular malformations. The prominent cardiac defects in NS are pulmonary valve stenosis and hypertrophic cardiomyopathy. Gain-of-function mutations protein tyrosine phosphatase Shp2 have been identified 50% of families. We created a mouse model selective overexpression mutant (Q79R-Shp2) developing endocardial cushions. In our model, Cre recombinase driven by Tie2 promoter irreversibly activates...
The identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) families with congenital heart disease has facilitated mechanistic studies various cardiovascular defects. However, roles normal and mutant Shp2 developing are still poorly understood. Furthermore, it remains unclear how loss-of-function (LOF) cause LEOPARD Syndrome (also termed Noonan multiple lentigines), which is characterized by defects such as pulmonary valve stenosis hypertrophic cardiomyopathy...
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...
Background The enzyme hexokinase‐2 ( HK 2) phosphorylates glucose, which is the initiating step in virtually all glucose utilization pathways. Cardiac hypertrophy associated with a switch towards increased metabolism and decreased fatty acid metabolism. Recent evidence suggests that compensatory to down‐regulated during is, fact, beneficial. Therefore, we hypothesized increasing by 2 overexpression would decrease cardiac hypertrophy. Methods Results Mice cardiac‐specific displayed response...
The biochemical differences between the 2 mammalian cardiac myosin heavy chains (MHCs), alpha-MHC and beta-MHC, are well described, but physiological consequences of basal isoform expression shifts in response to altered load not clearly understood. Mature human ventricle contains primarily beta-MHC isoform. However, can be detected healthy appears significantly downregulated failing hearts. unique properties might offer functional advantages a heart that is expressing only This hypothesis...
TEA domain transcription factor-1 (TEAD-1) is essential for proper heart development and implicated in cardiac specific gene expression the hypertrophic response of primary cardiomyocytes to hormonal mechanical stimuli, its activity increases pressure-overloaded hypertrophied rat heart. To investigate whether TEAD-1 an vivo modulator hypertrophy, we developed transgenic mice expressing hemagglutinin-tagged under control muscle creatine kinase promoter. We show that a sustained increase...
The protein tyrosine phosphatase Shp2 ( PTPN11 ) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal astroglia cell fate decisions. However, its roles the ventral telencephalon during oligodendrogenesis remain largely unknown. gain-of-function (GOF) mutations are observed Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, neurocognitive abnormalities. To gain insight into requirements...
The molecular pathways regulating valve development are only partially understood. Recent studies indicate that dysregulation of mitogen-activated protein kinase (MAPK) signaling might play a major role in the pathogenesis congenital valvular malformations, and, this study, we explored extracellular signal-regulated (ERK) 1/2 activation primordia expressing Noonan syndrome mutation Q79R-Shp2. is an autosomal dominant disease characterized by dysmorphic features and cardiac abnormalities,...
Cardiac injury induces myocyte apoptosis and necrosis, resulting in the secretion and/or release of intracellular proteins. Currently, myocardial can be detected by analysis a limited number biomarkers blood or coronary artery perfusate. However, complete proteomic signature protein from necrotic cardiac myocytes is unknown. Therefore, we undertook proteomic-based study proteins released cultured neonatal rat response to H2O2 (necrosis) staurosporine (apoptosis) identify novel specific...
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder with marked skeletal fragility and increased recognition as pleiotropic type I collagenopathy. The impact of OI-causing gene variants on cardiac health lifespan just beginning to be understood. To begin investigate manifestations collagen variants, we utilized the osteogenesis murine ( oim/oim) model examine survival age, well function expression at 4 18 months age. We determined male oim/oim mice had 50% decreased by age...
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...