An Exercise Immune Fitness Test to Unravel Disease Mechanisms—A Proof-of-Concept Heart Failure Study

Galyna Bondar; Abhinandan Das Mahapatra; Tra-Mi Bao; Irina Silacheva; Adrian Hairapetian; Thomas Vu; Stephanie Su; Ananya Katappagari; Liana Galan; Joshua Chandran; Ruben Adamov; Lorenzo Mancusi; Isabel Lai; Anca Rahman; Tristan Grogan; Jeffrey J. Hsu; Monica Cappelletti; Peipei Ping; David Elashoff; Elaine F. Reed; Mario C. Deng

doi:10.3390/jcm13113200

Journal of Clinical Medicine (May 2024)

An Exercise Immune Fitness Test to Unravel Disease Mechanisms—A Proof-of-Concept Heart Failure Study

Galyna Bondar,
Abhinandan Das Mahapatra,
Tra-Mi Bao,
Irina Silacheva,
Adrian Hairapetian,
Thomas Vu,
Stephanie Su,
Ananya Katappagari,
Liana Galan,
Joshua Chandran,
Ruben Adamov,
Lorenzo Mancusi,
Isabel Lai,
Anca Rahman,
Tristan Grogan,
Jeffrey J. Hsu,
Monica Cappelletti,
Peipei Ping,
David Elashoff,
Elaine F. Reed,
Mario C. Deng

Affiliations

Galyna Bondar: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Abhinandan Das Mahapatra: Strand NGS, Strand Life Sciences Pvt. Ltd., San Francisco, CA 94104, USA
Tra-Mi Bao: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Irina Silacheva: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Adrian Hairapetian: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Thomas Vu: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Stephanie Su: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Ananya Katappagari: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Liana Galan: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Joshua Chandran: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Ruben Adamov: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Lorenzo Mancusi: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Isabel Lai: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Anca Rahman: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Tristan Grogan: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Jeffrey J. Hsu: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Monica Cappelletti: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Peipei Ping: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
David Elashoff: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Elaine F. Reed: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA
Mario C. Deng: David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA

DOI: https://doi.org/10.3390/jcm13113200
Journal volume & issue: Vol. 13, no. 11
p. 3200

Abstract

Read online

Background: Cardiorespiratory fitness positively correlates with longevity and immune health. Regular exercise may provide health benefits by reducing systemic inflammation. In chronic disease conditions, such as chronic heart failure and chronic fatigue syndrome, mechanistic links have been postulated between inflammation, muscle weakness, frailty, catabolic/anabolic imbalance, and aberrant chronic activation of immunity with monocyte upregulation. We hypothesize that (1) temporal changes in transcriptome profiles of peripheral blood mononuclear cells during strenuous acute bouts of exercise using cardiopulmonary exercise testing are present in adult subjects, (2) these temporal dynamic changes are different between healthy persons and heart failure patients and correlate with clinical exercise-parameters and (3) they portend prognostic information. Methods: In total, 16 Heart Failure (HF) patients and 4 healthy volunteers (HV) were included in our proof-of-concept study. All participants underwent upright bicycle cardiopulmonary exercise testing. Blood samples were collected at three time points (TP) (TP1: 30 min before, TP2: peak exercise, TP3: 1 h after peak exercise). We divided 20 participants into 3 clinically relevant groups of cardiorespiratory fitness, defined by peak VO2: HV (n = 4, VO2 ≥ 22 mL/kg/min), mild HF (HF1) (n = 7, 14 2 n = 9, VO2 ≤ 14 mL/kg/min). Results: Based on the statistical analysis with 20–100% restriction, FDR correction (p-value 0.05) and 2.0-fold change across the three time points (TP1, TP2, TP3) criteria, we obtained 11 differentially expressed genes (DEG). Out of these 11 genes, the median Gene Expression Profile value decreased from TP1 to TP2 in 10 genes. The only gene that did not follow this pattern was CCDC181. By performing 1-way ANOVA, we identified 8/11 genes in each of the two groups (HV versus HF) while 5 of the genes (TTC34, TMEM119, C19orf33, ID1, TKTL2) overlapped between the two groups. We found 265 genes which are differentially expressed between those who survived and those who died. Conclusions: From our proof-of-concept heart failure study, we conclude that gene expression correlates with VO2 peak in both healthy individuals and HF patients, potentially by regulating various physiological processes involved in oxygen uptake and utilization during exercise. Multi-omics profiling may help identify novel biomarkers for assessing exercise capacity and prognosis in HF patients, as well as potential targets for therapeutic intervention to improve VO2 peak and quality of life. We anticipate that our results will provide a novel metric for classifying immune health.

Published in Journal of Clinical Medicine

ISSN: 2077-0383 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/jcm

About the journal

Abstract

Keywords