Ivan Luptak, MD, PhD
Assistant Professor
Boston University School of Medicine
Dept of Medicine
Cardiovascular Medicine

MD, Comenius University
PhD, Comenius University




Metabolic syndrome is a cluster of obesity-related metabolic abnormalities that affects an estimated 34% of the U.S. population and increases the risk of developing cardiovascular disease, including metabolic heart disease (MHD). MHD, which is characterized by left ventricular (LV) hypertrophy and impaired diastolic relaxation, culminates in diastolic heart failure. Currently there is no specific therapy for diastolic heart failure. We made a novel observation that a diet high in fat and sucrose (HFHS) leads to MHD and causes an abnormal increase in the intracellular concentration of sodium (Na) in the heart. It’s known that elevated cytosolic Na may deplete mitochondrial calcium and lead to both decreased ATP and increased damaging reactive oxygen species (ROS) production.
We hypothesize that elevated myocardial Na leads to impaired mitochondrial calcium signaling in MHD. As result, mitochondria produce less ATP and more ROS. Consequently, less ATP is available to fuel cell functions such as relaxation and contraction. Of the two, myocardial relaxation is more susceptible to the lack of ATP, thus diastolic dysfunction ensues.
To test our hypothesis, we will use mice fed HFHS diet that become obese and develop MHD. Our aims will test 1) the role of Na elevation in decreased ATP and increased ROS production, 2) the role of Na-induced decreased ATP production in energetic and contractile dysfunction and 3) the role of Na-induced increased ROS production in mediating MHD.
To address these aims, intracellular Na, mitochondrial calcium and mitochondrial ROS will be manipulated in vitro and ex vivo using a variety of pharmacologic and transgenic interventions. Mitochondrial function and ROS production will be assessed in isolated mitochondria, calcium regulation and function will be assessed in isolated myocytes, and cardiac intracellular Na and energetics will be assessed in beating hearts using 23Na and 31P NMR spectroscopy.

Member
Boston University
Whitaker Cardiovascular Institute



2015-2020 American Heart Association: Fellow to Faculty Transition Award



PRECLINICAL RESEARCH PROGRAM
01/18/2019 - 01/17/2021 (PI)
AMGEN, INC

Elevated intracellular sodium worsens mitochondrial ROS and ATP production in obesity indiced distol
07/01/2015 - 06/30/2020 (PI)
American Heart Assoc


Title


Yr Title Project-Sub Proj Pubs

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

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  1. Goodman JB, Qin F, Morgan R, Chambers JM, Croteau D, Siwik DA, Hobai I, Panagia M, Luptak I, Bachschmid M, Tong XY, Pimentel DR, Cohen RA, Colucci WS. Redox-Resistant SERCA Attenuates Oxidant-Stimulated Mitochondrial Calcium and Apoptosis in Cardiac Myocytes and Pressure Overload-Induced Myocardial Failure in Mice. Circulation. 2020 Oct 20.View Related Profiles. PMID: 33076678
     
  2. Burns M, Rizvi SHM, Tsukahara Y, Pimentel DR, Luptak I, Hamburg NM, Matsui R, Bachschmid MM. Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases. Int J Mol Sci. 2020 Sep 16; 21(18).View Related Profiles. PMID: 32948023
     
  3. Croteau D, Qin F, Chambers JM, Kallick E, Luptak I, Panagia M, Pimentel DR, Siwik DA, Colucci WS. Differential Effects of Sacubitril/Valsartan on Diastolic Function in Mice With Obesity-Related Metabolic Heart Disease. JACC Basic Transl Sci. 2020 Sep; 5(9):916-927.View Related Profiles. PMID: 33015414
     
  4. Panagia M, Yang J, Gale E, Wang H, Luptak I, Chen HH, Patel D, Croteau D, Pimentel DR, Bachschmid MM, Colucci WS, Ran C, Sosnovik DE. A novel tracer for in vivo optical imaging of fatty acid metabolism in the heart and brown adipose tissue. Sci Rep. 2020 07 08; 10(1):11209.View Related Profiles. PMID: 32641756
     
  5. Panagia M, He H, Baka T, Pimentel DR, Croteau D, Bachschmid MM, Balschi JA, Colucci WS, Luptak I. Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease. NMR Biomed. 2020 05; 33(5):e4258.View Related Profiles. PMID: 32066202
     
  6. Kimura T, Ferran B, Tsukahara Y, Shang Q, Desai S, Fedoce A, Pimentel DR, Luptak I, Adachi T, Ido Y, Matsui R, Bachschmid MM. Production of adeno-associated virus vectors for in vitro and in vivo applications. Sci Rep. 2019 09 19; 9(1):13601.View Related Profiles. PMID: 31537820
     
  7. Luptak I, Morgan R, Baka T, Croteau D, Moverman D, Sarnak H, Kirber M, Bachschmid MM, Colucci WS, Pimentel DR. Genetically targeted fluorescent probes reveal dynamic calcium responses to adrenergic signaling in multiple cardiomyocyte compartments. Int J Biochem Cell Biol. 2019 09; 114:105569.View Related Profiles. PMID: 31299273
     
  8. Luptak I, Croteau D, Valentine C, Qin F, Siwik DA, Remick DG, Colucci WS, Hobai IA. Myocardial Redox Hormesis Protects the Heart of Female Mice in Sepsis. Shock. 2019 07; 52(1):52-60.View Related Profiles. PMID: 30102640
     
  9. Luptak I, Qin F, Sverdlov AL, Pimentel DR, Panagia M, Croteau D, Siwik DA, Bachschmid MM, He H, Balschi JA, Colucci WS. Energetic Dysfunction Is Mediated by Mitochondrial Reactive Oxygen Species and Precedes Structural Remodeling in Metabolic Heart Disease. Antioxid Redox Signal. 2019 09 01; 31(7):539-549.View Related Profiles. PMID: 31088291
     
  10. Yunis A, Doros G, Luptak I, Connors LH, Sam F. Use of Ventilatory Efficiency Slope as a Marker for Increased Mortality in Wild-Type Transthyretin Cardiac Amyloidosis. Am J Cardiol. 2019 07 01; 124(1):122-130.View Related Profiles. PMID: 31053293
     
Showing 10 of 37 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 37 publications over 16 distinct years, with a maximum of 5 publications in 2019 and 2020

YearPublications
20011
20023
20031
20041
20054
20073
20112
20123
20132
20142
20151
20161
20171
20182
20195
20205

In addition to these self-described keywords below, a list of MeSH based concepts is available here.

ATP
cardiomyopathy
diastolic dysfunction
energetic metabolism
heart failure
intracellular sodium
mitochondria
NMR spectroscopy
obesity
Contact for Mentoring:

650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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