A5050726858- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Cardiovascular Function and Risk Factors
- Metabolism and Genetic Disorders
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Fatty Acid Research and Health
- Cardiac Ischemia and Reperfusion
- Cardiomyopathy and Myosin Studies
- Pulmonary Hypertension Research and Treatments
- Metabolomics and Mass Spectrometry Studies
- Photosynthetic Processes and Mechanisms
- Electron Spin Resonance Studies
- Diet, Metabolism, and Disease
- Cardiovascular Effects of Exercise
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular and exercise physiology
- Cell death mechanisms and regulation
- Congenital Heart Disease Studies
- Cannabis and Cannabinoid Research
- Eicosanoids and Hypertension Pharmacology
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
University of Colorado Anschutz Medical Campus
2015-2025
University of Colorado Denver
2013-2024
Children's Hospital Colorado
2013-2024
University of Colorado Boulder
2007-2022
The Medical Center of Aurora
2022
University of Colorado System
2021
University of Alabama at Birmingham
2017
Fraternal Order of Eagles
2017
University of Iowa
2017
Washington University in St. Louis
2017
Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity diabetes mellitus. However, mechanisms linking overload mitochondrial are incompletely understood.To elucidate the for adaptations postnatal hearts vivo.Using a transgenic mouse model lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) cardiomyocytes, we show that modestly myocardial fatty acid uptake leads structural...
A controversy in the field of bioenergetics has been whether mitochondria are capable sequestering enough Ca2+ from cytosolic pulses to raise their intramitochondrial free level ([Ca2+]m). This is significant because an increase [Ca2+]m linked cellular metabolic rate through various mechanisms. To resolve this question, we exposed isolated liver physiological type produced using a pulse-generating system (Sparagna, G. C., Gunter, K. K., and T. E. (1994) Anal. Biochem. 219, 96-103). We then...
Apoptosis has been identified recently as a component of many cardiac pathologies. However, the potential triggers programmed cell death in heart and involvement specific metabolic pathway(s) are less well characterized. Detachment cytochrome c from mitochondrial inner membrane is necessary first step for release into cytosol initiation apoptosis. The saturated long chain fatty acid, palmitate, induces apoptosis rat neonatal cardiomyocytes diminishes content anionic phospholipid,...
The mitochondrial phospholipid cardiolipin is required for optimal respiration. In this study, molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) Sprague-Dawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) young aortic-constricted SHHF also to investigate alterations aging versus pathology. Additionally, was analyzed human hearts...
After cardiac ischemia, long-chain fatty acids, such as palmitate, increase in plasma and heart. Palmitate has previously been shown to cause apoptosis myocytes. Cultured neonatal rat myocytes were studied assess mitochondrial alterations during apoptosis. Phosphatidylserine translocation caspase 3-like activity confirmed the apoptotic action of palmitate. Cytosolic cytochrome cwas detected at 8 h plateaued 12 h. The membrane potential (ΔΨ) tetramethylrhodamine ethyl ester-loaded decreased...
Here we present for the first time a three-dimensional cryo-EM map of Saccharomyces cerevisiae respiratory supercomplex composed dimeric complex III flanked on each side by one monomeric IV. A precise fit existing atomic x-ray structures from yeast and IV bovine heart into resulted in pseudo-atomic model structure supercomplex. The distance between cytochrome c binding sites complexes is about 6 nm, which supports proposed channeling individual complexes. opposing surfaces differ...
Negative alterations of mitochondria are known to occur in heart failure (HF). This study investigated the novel mitochondrial-targeted therapeutic agent elamipretide on mitochondrial and supercomplex function failing human hearts ex vivo. Freshly explanted nonfailing ventricular tissue from children adults was treated with elamipretide. Mitochondrial oxygen flux, complex (C) I CIV activities, in-gel activity assembly were measured. impaired heart, CI supercomplex-associated significantly...
The most severe manifestation of peripheral arterial disease (PAD) is critical limb ischemia (CLI). CLI patients suffer high rates amputation and mortality; accordingly, there remains a clear need both to better understand develop more effective treatments. Gastrocnemius muscle was obtained from 32 older (51–84 years) non-PAD controls, 27 claudicating PAD (ankle-brachial index [ABI] 0.65 ± 0.21 SD), 19 (ABI 0.35 0.30 SD) for whole transcriptome sequencing comprehensive mitochondrial...
Electrospray ionization mass spectrometry has previously been used to probe qualitative changes in the phospholipid cardiolipin (CL), but it rarely a quantitative manner. We assessed amount of individual molecular species cardiac CL present model congestive heart failure using 1,1',2,2'-tetramyristoyl as an internal standard. There was linear relationship between ratio negative ion ([M-H]-) current from four different reference standards and [M-H]- standard, function concentration species....
The effect of endurance training on the resistance heart to left ventricular (LV) functional deficit and infarction after a transient regional ischemia subsequent reperfusion was examined. Female Sprague-Dawley rats were randomly assigned an exercise (Tr) group or sedentary (Sed) control group. After 20 wk training, hearts excised, perfused, instrumented for assessment LV mechanical function, anterior descending coronary artery occluded induce (1 h) that followed by 2 h reperfusion....
Cardiolipin (CL) is responsible for modulation of activities various enzymes involved in oxidative phosphorylation. Although energy production decreases heart failure (HF), regulation cardiolipin during HF development unknown. Enzymes cardiac synthesis and remodeling were studied spontaneously hypertensive (SHHF) rats, explanted hearts from human patients, nonfailing Sprague Dawley (SD) rats. The biosynthetic cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they immature, which is barrier to modeling adult-onset cardiovascular disease. Here, we sought develop simple method that could drive cultured hiPSC-CMs toward maturity across number of phenotypes, with the aim utilizing mature model human were in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics adult...
Lactate is an important signaling molecule with autocrine, paracrine and endocrine properties involved in multiple biological processes including regulation of gene expression metabolism. Levels lactate are increased chronically diseases associated cardiometabolic disease such as heart failure, type 2 diabetes, cancer. Using neonatal ventricular myocytes, we tested the hypothesis that chronic exposure could decrease activity cardiac mitochondria lead to metabolic inflexibility other...
The saturated fatty acid palmitate induces apoptosis in neonatal rat cardiomyocytes. This is associated with early mitochondrial release of cytochrome c and a subsequent loss membrane potential. Recent reports implicate role for reactive oxygen species (ROS) palmitate-induced apoptosis. We studied the ROS cardiomyocyte report no evidence involvement. production, nitric oxide nuclear factor-kappaB activation were not increased above those observed using nonapoptotic oleate. Indeed, production...
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...
Potential regulation of two factors linked to physiological outcomes with left ventricular (LV) hypertrophy, resistance apoptosis, and matching metabolic capacity, by the transcription factor cyclic-nucleotide regulatory element binding protein (CREB), was examined in models LV hypertrophy: involuntary treadmill running female Sprague-Dawley rats voluntary exercise wheel C57Bl/6 mice. Comparative studies were performed pathological hypertrophy failure: spontaneously hypertension heart...