A5073352935- Cardiac Ischemia and Reperfusion
- Connective tissue disorders research
- Kawasaki Disease and Coronary Complications
- Mechanical Circulatory Support Devices
- Glycosylation and Glycoproteins Research
- Cardiovascular Function and Risk Factors
- Congenital Heart Disease Studies
- Thyroid Disorders and Treatments
- Cardiovascular Issues in Pregnancy
- Galectins and Cancer Biology
- Coronary Artery Anomalies
- Cardiomyopathy and Myosin Studies
- Aortic Disease and Treatment Approaches
- Neuroscience of respiration and sleep
- Cardiac Valve Diseases and Treatments
- Vascular anomalies and interventions
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Carbohydrate Chemistry and Synthesis
- Nitric Oxide and Endothelin Effects
- Congenital heart defects research
- Cardiovascular Effects of Exercise
- Cardiac Arrest and Resuscitation
- Signaling Pathways in Disease
Seattle Children's Hospital
2014-2025
Sandia National Laboratories
2021-2025
Boehringer Ingelheim (United States)
2024
University of Washington
2013-2023
Washington Center
2022
Seattle University
2012-2014
University of Minnesota
2012
University of Utah
2012
University of Alabama at Birmingham
2012
Children's Hospital of Los Angeles
2010
Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, current standard therapy most centers.
AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested be involved, such as p70 ribosomal S6 kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, is accompanied by increased O-GlcNAcylation, which reversed activation. Decreasing O-GlcNAcylation inhibitors the...
In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by PPARgamma coactivator-1 (PGC-1) family transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity preference for glucose metabolism pathways. Interestingly, despite reduced activity, these are associated with biogenesis, at least initially. The transcription factors that regulate changes setting...
The hexosamine biosynthesis pathway (HBP) branches from glycolysis and forms UDP-GlcNAc, the moiety for O-linked β-GlcNAc (O-GlcNAc) post-translational modifications. An inability to directly measure HBP flux has hindered our understanding of factors regulating protein O-GlcNAcylation. Our goals in this study were (i) validate a LC-MS method that assesses as UDP-GlcNAc (13C)-molar percent enrichment (MPE) concentration (ii) determine whether glucose availability or workload regulate cardiac...
Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe this population produces improvements postoperative clinical outcome.The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial younger than 2 years old undergoing heart surgery with Enrollment stratified by surgical diagnosis. Time to extubation (TTE) outcome. Patients received intravenous...
Background— A functional polymorphism in the inhibitory IgG-Fc receptor gene Fc γ RIIB influences intravenous immunoglobulin (IVIG) response Kawasaki disease (KD), a vasculitis preferentially affecting coronary arteries children. We tested hypothesis that polymorphisms activating receptors ( RIIA , RIIIA and RIIIB ) also influence susceptibility, IVIG treatment response, artery patients with KD. Methods Results— genotyped using pyrosequencing 443 KD, including 266 trios 150 single...
OBJECTIVES: Patients with Kawasaki disease can develop life-altering coronary arterial abnormalities, particularly in those resistant to intravenous immunoglobulin (IVIg) therapy. We tested the tumor necrosis factor α receptor antagonist etanercept for reducing both IVIg resistance and artery (CA) progression. METHODS: In a double-blind multicenter trial, patients received either (0.8 mg/kg; n = 100) or placebo (n 101) subcutaneously starting immediately after infusion. was primary outcome...
Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation lipid metabolism. Mouse models likewise demonstrated the absence PPARα is associated decreased survival injury, specifically heart. Using clinically relevant mouse model early sepsis, we found heart function increases in wild-type (WT) mice over first 24 h but...
Atrioventricular septal defects (AVSDs) are a frequent but not universal component of Down syndrome (DS), while AVSDs in otherwise normal individuals have no well-defined genetic basis. The contribution copy number variation (CNV) to specific congenital heart disease (CHD) phenotypes including AVSD is unknown. We hypothesized that de novo CNVs on chromosome 21 might cause isolated sporadic AVSDs, and separately throughout the genome constitute an additional risk factor for patients with DS....
Background Protein posttranslational modifications by O ‐linked β‐N‐acetylglucosamine (O‐GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood. In other organs, O‐GlcNAc promotes adaptation to acute physiological stressors; however, prolonged elevations believed be detrimental. We hypothesize that early O‐GlcNAcylation improves function during initial response pressure overload but sustained established pathological hypertrophy...
Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout (Myc) attenuated hypertrophy and decreased expression metabolic genes after aortic constriction. Accordingly, we assessed interplay between Myc, substrate oxidation cardiac function during early pressure overload hypertrophy. Mice with specific, inducible Myc (MycKO-TAC) non-transgenic littermates (Cont-TAC) were subjected to transverse constriction (TAC; n = 7/group)....
Pyruvate produces inotropic responses in the adult reperfused heart. oxidation and anaplerotic entry into tricarboxylic acid (TCA) cycle via carboxylation are linked to stimulation of contractile function. The goals this study were determine if these metabolic pathways operate maintained developing myocardium after reperfusion. Immature male swine (age: 10–18 days) subjected cardiopulmonary bypass (CPB). Intracoronary infusion [2- 13 C]pyruvate (to achieve an estimated final concentration 8...
Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant to test the hypothesis that T3 modulates pyruvate entry into citric acid cycle (CAC), thereby providing energy support for improved function ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-(13)Carbon((13)C)]pyruvate 40 min (8 mM) during control aerobic conditions (control) or...