Serum multi-omics analysis in hindlimb unloading mice model: Insights into systemic molecular changes and potential diagnostic and therapeutic biomarkers
Zeinab Ibrahim,
Naveed A. Khan,
Rizwan Qaisar,
Mohamed A. Saleh,
Ruqaiyyah Siddiqui,
Hamza M. Al-Hroub,
Alexander D. Giddey,
Mohammad Harb Semreen,
Nelson C. Soares,
Adel B. Elmoselhi
Affiliations
Zeinab Ibrahim
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Naveed A. Khan
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Microbiota Research Center, Istinye University, Istanbul, 34010, Turkey
Rizwan Qaisar
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Mohamed A. Saleh
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
Ruqaiyyah Siddiqui
Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University Edinburgh, EH14 4AS UK; Microbiota Research Center, Istinye University, Istanbul, 34010, Turkey
Hamza M. Al-Hroub
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Alexander D. Giddey
Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
Mohammad Harb Semreen
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
Nelson C. Soares
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Laboratory of Proteomics, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA), Av.a Padre Cruz, Lisbon, 1649-016, Portugal; Centre for Toxicogenomics and Human Health (ToxOmics), NOVA School/ Faculdade de Lisboa, Lisbon, Portugal
Adel B. Elmoselhi
Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Corresponding author: Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah, P.O. Box 27272
Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.
