PhD Scientific Days 2023

Budapest, 22-23 June 2023

Translational Medicine - Posters P

Pretreatment with NAD+ Precursor (NMN) Attenuates Ischemic Injury and Improves Postischemic Cardiac Function in Aged Mouse Hearts

Előadó neve

Fülöp, Ágnes

Neptun code

V0IZY8

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36305808606

Előadó e-mail címe

fulop.agnes@med.semmelweis-univ.hu

Az előadás címe

Pretreatment with NAD+ Precursor (NMN) Attenuates Ischemic Injury and Improves Postischemic Cardiac Function in Aged Mouse Hearts

Szerző(k) neve és munkahelye

Ágnes Fülöp1, Vanessza Yit Sokpanya1, Zoltán Ungvári2,3, Zoltán Benyó1, Zsuzsanna Miklós1,4

1 Institute of Translational Medicine, Semmelweis University, Budapest
2 Department of Public Health, Semmelweis University, Budapest
3 Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
4 National Koranyi Institute for Pulmology, Budapest

Bemutatás módja

Poszter

Szekció

Translational Medicine - Posters P

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction

During aging, nicotinamide adenine dinucleotide (NAD+) depletion and the impairment of cardioprotection can be identified. We hypothesize that increased ischemic vulnerability of the heart in old age may be related to a decrease in NAD+ levels.

Aims

Our aim was to prove that treatment with NAD+ precursor (nicotinamide mononucleotide, NMN) improves heart function and reduces ischemic damage in old hearts.

Method

After pretreatment of young and old (4 and 26 months old) C57Bl/6N male mice with NMN (500 mg/kg/day ip.) or carrier (PBS) for 2 weeks echocardiographic examination was performed, then isolated hearts were perfused with constant pressure in the Langendorff system. The hearts were exposed to 23 minutes of total ischemia, followed by a 120-minute reperfusion period. Coronary flow and left ventricular (LV) pressure changes were measured, and LV infarct size was also determined.

Results

During echocardiography enlarged left ventricle was found, while the ejection fraction was also preserved in elderly hearts. NMN treatment did not affect the echocardiographic parameters. The ratio of the infarcted area in LV of old mice was significantly higher compared to the young mice. After NMN pretreatment, the myocardial infarction size of the old hearts decreased (young: 35±3%, old: 55±8%, young+NMN: 27±8 %; old+NMN: 22±5%; n=25,10,6,11; p<0.05 old vs. old+NMN and young vs. old). The postischemic coronary flow and the functional restitution of old hearts were impaired compared to the youngs (decreased LV pulse pressure, +dP/dt és –dP/dt), however, the NMN treatment compensated this impairment.

Conclusion

Pretreatment with NAD+ precursor does not affect the resting heart function, but at the same time it significantly reduces the consequences of cardiac ischemia; it has a favorable effect both on infarct size and on postischemic heart function.
In the future we plan to perform gene expression analysis for genes of several NAD+-dependent enzymes.

Funding

This study was supported by NKFIH K-125174, K-135683 and K-139230 as well as by 2020-1.1.6-JÖVŐ-2021-00010, TKP2021-EGA-25 and EFOP-3.6.3-VEKOP-16-2017-00009 grants.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Prof. Dr. Zoltán Benyó, Dr. Zsuzsanna Miklós

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7514

Start

11:00

End

11:05

Authors (legacy)

Ágnes Fülöp1, Vanessza Yit Sokpanya1, Zoltán Ungvári2,3, Zoltán Benyó1, Zsuzsanna Miklós1,4

1 Institute of Translational Medicine, Semmelweis University, Budapest
2 Department of Public Health, Semmelweis University, Budapest
3 Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
4 National Koranyi Institute for Pulmology, Budapest