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.

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



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



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.

  1. Wende AR, Kim J, Holland W, Wayment BE, O''Neill BT, Tuinei J, Brahma MK, Pepin ME, McCrory MA, Luptak I, Halade GV, Litwin SE, Abel ED. Glucose transporter 4 (GLUT4) deficient hearts develop maladaptive hypertrophy in response to physiologic or pathologic stresses. Am J Physiol Heart Circ Physiol. 2017 Aug 19; ajpheart.00101.2017. PMID: 28822962.
  2. Sverdlov AL, Elezaby A, Qin F, Behring JB, Luptak I, Calamaras TD, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Bachschmid MM, Colucci WS. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease. J Am Heart Assoc. 2016 Jan 11; 5(1).View Related Profiles. PMID: 26755553; PMCID: PMC4859372; DOI: 10.1161/JAHA.115.002555;.
  3. Miller EJ, Calamaras T, Elezaby A, Sverdlov A, Qin F, Luptak I, Wang K, Sun X, Vijay A, Croteau D, Bachschmid M, Cohen RA, Walsh K, Colucci WS. Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge. J Am Heart Assoc. 2015 Dec 31; 5(1).View Related Profiles. PMID: 26722122; PMCID: PMC4859355; DOI: 10.1161/JAHA.115.002277;.
  4. Elezaby A, Sverdlov AL, Tu VH, Soni K, Luptak I, Qin F, Liesa M, Shirihai OS, Rimer J, Schaffer JE, Wilson S C, Edward J M. Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload. J Mol Cell Cardiol. 2015 Feb; 79:275-83.View Related Profiles. PMID: 25497302; PMCID: PMC4301992; DOI: 10.1016/j.yjmcc.2014.12.001;.
  5. Sverdlov AL, Elezaby A, Behring JB, Bachschmid MM, Luptak I, Tu VH, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Colucci WS. High fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II. J Mol Cell Cardiol. 2015 Jan; 78:165-73.View Related Profiles. PMID: 25109264; PMCID: PMC4268348; DOI: 10.1016/j.yjmcc.2014.07.018;.
  6. Zhi H, Luptak I, Alreja G, Shi J, Guan J, Metes-Kosik N, Joseph J. Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast function. PLoS One. 2013; 8(12):e81612. PMID: 24349097; PMCID: PMC3859492; DOI: 10.1371/journal.pone.0081612;.
  7. Qin F, Siwik DA, Lancel S, Zhang J, Kuster GM, Luptak I, Wang L, Tong X, Kang YJ, Cohen RA, Colucci WS. Hydrogen peroxide-mediated SERCA cysteine 674 oxidation contributes to impaired cardiac myocyte relaxation in senescent mouse heart. J Am Heart Assoc. 2013 Aug; 2(4):e000184.View Related Profiles. PMID: 23963753; PMCID: PMC3828801; DOI: 10.1161/JAHA.113.000184;.
  8. Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang SS, Zhi H, Qin F, Jacobsen DW, Loscalzo J, Joseph J. Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res. 2012 Dec; 56(12):1812-24.View Related Profiles. PMID: 23097236; PMCID: PMC3546539; DOI: 10.1002/mnfr.201200386;.
  9. Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, Miller EJ, Verbeuren TJ, Walsh K, Cohen RA, Colucci WS. The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice. Circulation. 2012 Apr 10; 125(14):1757-64, S1-6.View Related Profiles. PMID: 22388319; PMCID: PMC3354628; DOI: 10.1161/CIRCULATIONAHA.111.067801;.
  10. Bugger H, Riehle C, Jaishy B, Wende AR, Tuinei J, Chen D, Soto J, Pires KM, Boudina S, Theobald HA, Luptak I, Wayment B, Wang X, Litwin SE, Weimer BC, Abel ED. Genetic loss of insulin receptors worsens cardiac efficiency in diabetes. J Mol Cell Cardiol. 2012 May; 52(5):1019-26. PMID: 22342406; PMCID: PMC3327790; DOI: 10.1016/j.yjmcc.2012.02.001;.
Showing 10 of 25 results. Show More

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

Bar chart showing 25 publications over 13 distinct years, with a maximum of 4 publications in 2005

YearPublications
20011
20023
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20073
20112
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20151
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20171
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
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650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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