News & Events
Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK -
Journal of Molecular and Cellular Cardiology
LSU Health Authors
Dr. David J. Lefer
- •Hydrogen Sulfide levels influence cardiac mitochondrial content.
- •Hydrogen Sulfide induces mitochondrial biogenesis in an AMPK-dependent manner.
- •Hydrogen Sulfide activates AMPK via the sulfhydration and inhibition of PP2A.
Hydrogen sulfide (H2S) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if H2S levels directly influenced cardiac mitochondrial content.
Mice deficient in the H2S-producing enzyme, cystathionine γ-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts. In contrast, mice overexpressing CSE (CSE Tg) and mice supplemented with the orally active H2S-releasing prodrug, SG-1002, displayed enhanced cardiac mitochondrial content. Additional analysis revealed that cardiac H2S levels influenced the nuclear localization and transcriptional activity of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) with higher levels having a positive influence and lower levels having a negative influence. Studies aimed at evaluating the underlying mechanisms found that H2S required AMP-activated protein kinase (AMPK) to induce PGC1α signaling and mitochondrial biogenesis. Finally, we found that restoring H2S levels with SG-1002 in the setting of heart failure increased cardiac mitochondrial content, improved mitochondrial respiration, improved ATP production efficiency, and improved cardiac function.
Together, these results suggest that hydrogen sulfide is an important regulator of cardiac mitochondrial content and establishes that exogenous hydrogen sulfide can induce mitochondrial biogenesis via an AMPK-PGC1α signaling cascade.
The Cardiovascular Center's own, David Polhemus, Ph.D., was profiled in an edition of the American Heart Association's Circulation Research journal. The journal discusses David's career from the start including his work with Cardiovascular Center director, David J. Lefer, Ph.D. See bellow for a small excerpt from the story as well as a link to the full text:
"Baseball aficionado, David Polhemus, is not one to let a strike avert a home run, nor does he allow a temporary setback in science prevent him from accomplishing the task at hand. David double majored in Chemistry and Economics at Emory University. He recently graduated with a PhD in Pharmacology and Experimental Therapeutics. David currently works in the Lefer lab at Louisiana State University’s Health Sciences Center in New Orleans."
Dr. Lefer Elected as President for the International Society of Heart Research North American Section
The NAM-ISHR section election was completed on November 30th where Dr. Lefer was voted President-elect. Dr. Lefer's term as President-elect will begin at the second council meeting at the NAM section meeting in Halifax, May 29-June 1, 2018. He will serve as President-elect until 2021 when he will begin his 3 year term as President, followed by a 3 year term as past-President.
Jessica Hartnett, Ph.D. Joins the CV Center as Research Coordinator
Dr. Hartnett joins the CV Center where she will serve as Research Coordinator under Dr. Danielle Gottlieb Sen. Her work will be based out of Children's Hospital in New Orleans. Dr. Hartnett graduated with honors from Tulane University School of Medicine where she recieved both her B.S. in Molecular Biology and French and her Ph.D with a concentration in Microbiology and Immunology.
Originally from St. Louis, Dr. Hartnett moved to New Orleans in 2004 to attend college and has made it her home since. Please join us in welcoming Dr. Hartnett to LSU Health New Orleans and the Cardiovascular Center of Excellence!
Dr. Lefer Appointed to Editorial Board for Journal of Molecular and Cellular Cardiology
Dr. Lefer has been appointed to the editorial board for the Journal of Molecular and Cellular Cardiology. His role will allow him to peer review publications for the journal relating to his concentrations in cardiovascular research.
We would like to acknowledge and congratulate one of the Cardiovascular Center of Excellence’s participants,
Hunter Hidalgo, for winning 1st place for 2017 Medical Student Research Day poster session.
Hunter’s poster, “Novel Rodent Model of Heart Failure with Preserved Ejection Fraction (HF-pEF)," was mentored by David J. Lefer, Ph.D.; Director, Cardiovascular Center of Excellence.
Please join us in congratulating the LSUHSC Cardiovascular Center of Excellence’s own David Polhemus, Ph.D. for receiving the Chancellor’s Award at the Graduate Research Day Award Ceremony this past Friday, November 3, 2017. The award is given to each year to “a high ranking graduating student who has done the most to promote the health sciences and the School before the public. Selection is made by a committee of the faculty appointed by the Dean, with consultation by members of the graduating class.”
Cardiovascular Center at the 2017 LSU Medical School Alumni Gala
Dr. Danielle Gottlieb Sen Nominated for New Orleans CityBusiness 2017 Women of the Year Award
Dr. Danielle Gottlieb Sen, M.D., M.S., MPH, of the Cardiovascular Center of Excellence and New Orleans Children's Hospital has been nominated by her peers as one of the Top 50 New Orleans' Woman of 2017 by New Orleans CityBusiness. Dr. Gottlieb Sen is both a Pediatric Cardiovascular Surgeon and Assistant Professor for the Department of Surgery. Additonally, her contribution to the Cardiovascular field has led to numerous advancements in Cardiovascular care for infants, childrens and adults. She is currently 1 out of approximately 15 female pediatric cardiovascular surgeons in North America.
"The 19th annual “Women of the Year” will be recognized at a noon luncheon Thursday, Nov. 2 at the Hyatt Regency, when an overall Woman of the Year will be announced. A special insert spotlighting all “Women of the Year” honorees will run in the Nov. 10 issue of CityBusiness." (via New Orleans City Buisness)
To view all the nominees for this prestigous award, click here New Orleans CityBusiness.
The Cardiovascular Center of Excellence, along with the Department of Pharmacology and Experimental Therapeutics, led an all LSU Health New Orleans original investigation into understanding, "Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of Neprilysin Activity in the Kidney." The investigation was led by CV Center members David Polhemus, Ph.D., Rishi Trivedi, Ph.D., Zhen Li and Amy Scarborough.
The study had a clear objective that 'investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism.'
The LSUHSC Center of Excellence in Cardiovascular Research hosts an exciting Cardiovascular Biology Seminar Series! Renowned scientists from prestigious and innovative institutions visit our Center regularly, sharing ideas and inspiring us to become the best. Please take a moment to view the LSU Health Science Center Medical School – Seminar Calendar. These seminars are golden opportunities to learn and visit with other scientists who aspire with similar interests.
To see the full list of presenters, click here.
LSUHSC Cardiovascular Center and Novo Biosciences Receive
$1.5 million NIH Grant to Study Myocardial Regeneration
New Orleans, LA (August 28, 2017) – LSU Health Cardiovascular Center of Excellence received a grant award from the National Heart, Lung and Blood Institute to research the development, a novel agent, MSI-1346, for therapeutic stimulation of heart regeneration following acute myocardial infarction and heart failure. The grant will provide more than $500,000 in funding over two years to LSUHSC-New Orleans along with Novo Biosciences in Bar Harbor, Maine in ongoing research for the project.
To read the full press release, click here.
$1.3 Million Grant to Fund Research on Reducing Cardiac Injury
with the First Drug-Eluting Guidewire
New Orleans, LA (August 11, 2017) – Adenopaint, LLC of Atlanta, GA, in conjunction with LSU Health New Orleans Cardiovascular Center of Excellence, has been awarded an SBIR Phase II grant in the amount of $1.3 million over two years by the National Heart, Lung and Blood Institute.
The funding will be used to study the company’s Adenowire, a novel guidewire coated with a drug which is released during percutaneous coronary intervention (PCI) to prevent and reverse vascular and cardiac tissue injury during PCI and therefore improve outcomes in cardiovascular diseases.
To read the full press release, click here.
$3.7 Million Grant to Fund Research on Novel Drug Targeting Heart Diseases
New Orleans, LA (August 11, 2017) – The Exscien Corporation of Louisville, KY, in conjunction with LSU Health New Orleans Cardiovascular Center of Excellence, has been awarded an SBIR Fast-Track grant in the amount of $3.7 million over three years by the National Heart, Lung and Blood Institute. The funding will be used to study the company’s first in a new class of drugs that repairs DNA damage to reduce cardiac tissue injury and improve outcomes in cardiovascular diseases.
To read the full press release, click here.
Cardiovascular Center Welcomes, Thomas E. Sharp III, Ph.D.
Dr. Thomas E. Sharp III joined the Cardiovascular Center of Excellence in July as a Postdoctoral Researcher. Dr. Sharp joins us from Temple University, Lewis Katz School of Medicine where he recieved his Ph.D. while working under renowned professor, John Elrod, Ph.D.. He will work alongside both Dr. Lefer and Dr. Goodchild to continue ongoing research.
Is Cardioprotection Dead?
David J. Lefer, Ph.D., along with Eduardo Marban, M.D., Ph.D., co-authored the latest abstract titled, 'Is Cardioprotection Dead?', issued by the American Heart Association's Circulation as part of their July 2017 issue.
Acknowledgments were also given to CV Students David J. Polhemus, Ph.D. and Rishi Trivedi, Ph.D. for their laboratory research.
The Abstract Summary
"For >4 decades, the holy grail in the treatment of acute myocardial infarction has been the mitigation of lethal injury. Despite promising initial results and decades of investigation by the cardiology research community, the only treatment with proven efficacy is early reperfusion of the occluded coronary artery. The remarkable record of failure has led us and others to wonder if cardioprotection is dead. The path to translation, like the ascent to Everest, is certainly littered with corpses. We do, however, highlight a therapeutic principle that provides a glimmer of hope: cellular postconditioning. Administration of cardiosphere-derived cells after reperfusion limits infarct size measured acutely, while providing long-term structural and functional benefits. The recognition that cell therapy may be cardioprotective, and not just regenerative, merits further exploration before we abandon the pursuit entirely."
David J. Lefer, PhD; Eduardo Marbán, MD, PhD, Is Cardioprotection Dead? American Heart Association, Circulation. 2017 Jul 4;136(1):98-109. doi: 10.1161/CIRCULATIONAHA.116.027039.
Dr. Wu Shares Insight on iPSCs for Cardiovascular Precision Medicine
Dr. Joseph C. Wu, Professor of Medicine and Radiology; Director of Stanford Cardiovascular Institute; Simon H. Stertzer Endowed Professorship from Stanford University School of Medicine presented the seminar on Induced pluripotent stem cells in cardiology, ‘iPSCs for Cardiovascular Precision Medicine’.
His presentation served as the 5th installment of the Cardiovascular Center of Excellence 2017 Seminar Series. During his visit in New Orleans, Dr. Wu met with LSUHSC professors and postdocs to discuss ongoing projects and potential collaborations.
His seminar covered a wide-range of topics discussing iPSC usage such as organ structure and function, patient phenotype, DNA sequence, gene expression and more. To learn more about Dr. Wu’s research, visit Nature Reviews – Cardiology.
Join us for our next Seminar Series guest, Dr. Christopher Kevil, Vice Chancellor of Research; Director of the Center for Cardiovascular Diseases and Sciences; Professor of Pathology at LSU Health Shreveport on Tuesday, August 8th!
Cardiovascular Center Faculty Published in Angewandte Chemie International
The combined research efforts by the Cardiovascular Center faculty contributed to the manuscript, ‘A Novel Esterase-sensitive Prodrug Approach for Controllable Delivery of Persulfide Species’, being accepted in the Angewandte Chemie International 2017 Edition.
Center faculty David J. Lefer, PhD; Chelsea L. Organ, PhD; Rishi K. Trivedi, PhD; and Zhen Li all made contributions to the study. The manuscript was peer-reviewed and accepted on July 12, 2017.
The Abstract Summary
“A new strategy to deliver a well-defined persulfide species in a biological medium is described herein. Under near physiological conditions, the persulfide prodrug can be activated by an esterase to generate a "hydroxyl methyl persulfide" intermediate, which rapidly collapses to form a defined persulfide. Such persulfide prodrugs can be used either as chemical tools to study persulfide chemistry and biology or for future development as H2S-based therapeutic reagents. Using the persulfide prodrugs developed in this study, the reactivity between S-methyl methanethiosulfonate (MMTS) with persulfide was unambiguously demonstrated. In addition, a representative prodrug exhibited potent cardioprotective effects in a murine model of myocardial ischemia-reperfusion (MI/R) injury with a bell shape therapeutic profile.”
Zheng, Y., Yu, B., Li, Z., Yuan, Z., Lefer, D. J., Wang, B., Wang, S., Organ, C. L. and Trivedi, R. K. (), A Novel Esterase-sensitive Prodrug Approach for Controllable Delivery of Persulfide Species. Angew. Chem. Int. Ed.. Accepted Author Manuscript. doi:10.1002/anie.201704117
Newest Faculty Appointment Dr. Papapetropoulos
The Cardiovascular Center of Excellence is proud to welcome Dr. Andreas Papapetropoulos, Ph.D. as the newest faculty appointment. Dr. Papapetropoulos will serve as a full-time professor and Director of the Seminar Series. He comes to us from the National and Kapodistrian University of Athens in Greece.
Congratulations to our Ph.D Recipients
Congratulations to the Cardiovascular Center of Excellence and Pharmacology Graduate Students for receiving their Ph.D.'s and beginning LSUHSC Medical School as part of the incoming 2017 Class:
(Left to Right): Dr. David Polhemus, Ph.D., Dr. Chelsea Organ, Ph.D., and Dr. Rishi Trivedi, Ph.D.
Cardiovascular Center Hosts 36th Annual ISHR Conference in New Orleans
The LSUHSC Cardiovascular Center of Excellence served as the host for the recent 36th Annual International Society for Heart Research - North American Section held at the Hilton New Orleans Riverside from May 30 - June 2. CV Center Director, Dr. David Lefer, served as the meeting organizer and was assisted by CV faculty and staff.
The meeting was comprised of more than 220 basic and clinical researchers from around the world covering the topic of "Translation of Cardiovascular Therapeutics to the Clinic". The event was a great success and wouldn't have been possible without the combined efforts of the CV Center and several other departments from LSUHSC. Special thanks to Dr. Vander Heide, Dr. Varner, Dr. Kapusta, Dr. Mungrue and Dr. Garder!
- Plenary lecture by Eric Olson (UTSW)
- Janice Pfeffer Distinguished Lecture by Tetsuji Miura (Sapporo Med Ctr)
- Outstanding Investigator Award lecture by Xander Wehrens (Baylor)
- Research Achievement Award lecture by Rong Tian (Univ Wash)
- Peter Harris Distinguished Scientist Award lecture by R. John Solaro (UIC)
Dinner Reception/Awards Ceremony and Social at Club XLIV and Encore for conference participants
Dr. Goodchild Named as Ad Hoc Specialist for AAALAC International
Dr. Traci Goodchild has been selected to serve a 3 year term as an ad hoc Specialist for AAALAC International. She will travel to different institutions as a site inspector evaluating their compliance with regulatory standards for the care and use of laboratory animals. There are only 25 out of 377 of AAALAC Specialists that hold only a PhD degree, with the others having been trained as veterinarians.