Education Commons^™

Evidence Of Glycolysis Up-Regulation And Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading Of The Failing Human Heart: Implications For Cardiac Reloading And Conditioning, Nikolaos A. Diakos, Sutip Navankasattusas, E. Dale Abel, Jared Rutter, Lauren Mccreath, Peter Ferrin, Stephen H. Mckellar, Dylan V. Miller, Song-Young Park, Russell S. Richardson, Ralph Deberardinis, James E. Cox, Abdallah G. Kfoury, Craig H. Selzman, Joseph C. Fang, Dean Y. Li, Stavros Drakos

Health and Kinesiology Faculty Publications

This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete …

Wnt5a-Jnk Regulation Of Vascular Insulin Resistance In Human Obesity, Melissa G. Farb, Shakun Karki, Song-Young Park, Samantha M. Saggese, Brian Carmine, Donald T. Hess, Caroline Apovian, Jessica L. Fetterman, Rosa Breton-Romero, Naomi M. Hamburg, Jose J. Fuster, Maria A. Zuriaga, Kenneth Walsh, Noyan Gokce

Health and Kinesiology Faculty Publications

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide …

Accuracy And Precision Of Quantitative 31p-Mrs Measurements Of Human Skeletal Muscle Mitochondrial Function, Gwenael Layec, J. R. Gifford, Joel D. Trinity, Corey R. Hart, Ryan S. Garten, Song-Young Park, Yann Le Fur, Eun-Kee Jeong, Russell S. Richardson

Health and Kinesiology Faculty Publications

Although theoretically sound, the accuracy and precision of 31P-magnetic resonance spectroscopy (31P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control [linear, kinetic, and multipoint adenosine diphosphate (ADP) and phosphorylation potential], this study sought to determine the accuracy and precision of 31P-MRS assessments of peak mitochondrial adenosine-triphosphate (ATP) synthesis rate utilizing directly measured peak respiration (State 3) in permeabilized skeletal muscle fibers. In 23 subjects of different fitness levels, 31P-MRS during a 24-s maximal isometric knee extension and high-resolution respirometry in muscle fibers from the vastus lateralis was performed. Although significantly …

Mitochondrial Function In Heart Failure: The Impact Of Ischemic And Non-Ischemic Etiology, Song-Young Park, Joel D. Trinity, J. R. Gifford, Nikolaos A. Diakos, Lauren Mccreath, Stavros Drakos, Russell S. Richardson

Health and Kinesiology Faculty Publications

Background

Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown.

Methods and results

To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n = 17), niHF (n = 18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I + …

Impact Of Aerobic And Anaerobic Exercise Training On Oxidative Stress And Antioxidant Defense In Athletes, Song-Young Park, Yi Sub Kwak

Health and Kinesiology Faculty Publications

Exercise mediates an excessive free radical production leading to oxidative stress (OS). The body has natural antioxidant systems that help decrease OS, and these systems may be enhanced with exercise training. However, only a few studies have investigated the differences in resting OS and antioxidant capacity (AOC) between aerobically trained athletes (ET), anaerobically trained athletes (RT), and untrained individuals (UT). Therefore, this study sought to investigate the resting and postexercise OS and AOC in ET, RT, and UT. Sixty healthy young males (26.6±0.8 yr) participated in this study. Subjects were divided into three groups, ET, RT, and UT by distinct …

Exercise Training Improves Vascular Mitochondrial Function, Song-Young Park, Matthew J. Rossman, J. R. Gifford, Leena P. Bharath, Johann Bauersachs, Russell S. Richardson, E. Dale Abel, J. David Symons, Christian Riehle

Health and Kinesiology Faculty Publications

Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state …

Impact Of Age On The Vasodilatory Function Of Human Skeletal Muscle Feed Arteries, Song-Young Park, S. J. Ives, J. R. Gifford, R. H. I. Andtbacka, John R. Hyngstrom, Van Reese, Gwenael Layec, Leena P. Bharath, J. David Symons, Russell S. Richardson

Health and Kinesiology Faculty Publications

Although advancing age is often associated with attenuated skeletal muscle blood flow and skeletal muscle feed arteries (SMFAs) have been recognized to play a regulatory role in the vasculature, little is known about the impact of age on the vasodilatory capacity of human SMFAs. Therefore, endothelium-dependent and -independent vasodilation were assessed in SMFAs (diameter: 544 ± 63 μm) obtained from 24 (equally represented) young (33 ± 2 yr) and old (71 ± 2 yr) subjects in response to three stimuli: 1) flow-induced shear stress, 2) ACh, and 3) sodium nitropusside (SNP). Both assessments of endothelium-dependent vasodilation, flow …