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Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts
- Source :
- Am J Physiol Heart Circ Physiol
- Publication Year :
- 2021
- Publisher :
- American Physiological Society, 2021.
-
Abstract
- Sphingosine-1-phosphate (S1P) is a bioactive mediator in inflammation. Dysregulated S1P is demonstrated as a cause of heart failure (HF). However, the time-dependent and integrative role of S1P interaction with receptors in HF is unclear after myocardial infarction (MI). In this study, the sphingolipid mediators were quantified in ischemic human hearts. We also measured the time kinetics of these mediators post-MI in murine spleen and heart as an integrative approach to understand the interaction of S1P and respective S1P receptors in the transition of acute (AHF) to chronic HF (CHF). Risk-free 8-12 wk male C57BL/6 mice were subjected to MI surgery, and MI was confirmed by echocardiography and histology. Mass spectrometry was used to quantify sphingolipids in plasma, infarcted heart, spleen of mice, and ischemic and healthy human heart. The physiological cardiac repair was observed in mice with a notable increase of S1P quantity (pmol/g) in the heart and spleen significantly reduced in patients with ischemic HF. The circulating murine S1P levels were increased during AHF and CHF despite lowered substrate in CHF. The S1PR1 receptor expression was observed to coincide with the respective S1P quantity in mice and human hearts. Furthermore, selective S1P1 agonist limited inflammatory markers CCL2 and TNF-alpha and accelerated reparative markers ARG-1 and YM-1 in macrophages in the presence of Kdo2-Lipid A (KLA; potent inflammatory stimulant). This report demonstrated the importance of S1P/S1PR1 signaling in physiological inflammation during cardiac repair in mice. Alteration in these axes may serve as the signs of pathological remodeling in patients with ischemia. NEW & NOTEWORTHY Previous studies indicate that sphingosine-1-phosphate (S1P) has some role in cardiovascular disease. This study adds quantitative and integrative systems-based approaches that are necessary for discovery and bedside translation. Here, we quantitated sphinganine, sphingosine, sphingosine-1-phosphate (S1P) in mice and human cardiac pathobiology. Interorgan S1P quantity and respective systems-based receptor activation suggest cardiac repair after myocardial infarction. Thus, S1P serves as a therapeutic target for cardiac protection in clinical translation.
- Subjects :
- Male
medicine.medical_specialty
Physiology
Myocardial Infarction
Spleen
Disease
Mice
chemistry.chemical_compound
Sphingosine
Lectins
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Regeneration
Myocytes, Cardiac
Myocardial infarction
Sphingosine-1-phosphate
Sphingosine-1-Phosphate Receptors
Cells, Cultured
Chemokine CCL2
Heart Failure
Arginase
Tumor Necrosis Factor-alpha
business.industry
Macrophages
LC/MS
medicine.disease
ischemic heart disease
beta-N-Acetylhexosaminidases
Mice, Inbred C57BL
medicine.anatomical_structure
chemistry
Heart failure
Cardiac repair
sphingosine-1-phosphate
Cardiology
lipids (amino acids, peptides, and proteins)
Lysophospholipids
Cardiology and Cardiovascular Medicine
business
Research Article
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 321
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....9e3e099105e5ea2e834e890c2fb5cf05