|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Health Sciences / Faculty of Health Sciences >
Peer-reviewed Journal Articles, etc >
Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts
| Title: | Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts |
| Authors: | Gowda, SiddabasaveGowda B. Browse this author →KAKEN DB | | Gowda, Divyavani Browse this author | | Kain, Vasundhara Browse this author | | Chiba, Hitoshi Browse this author →KAKEN DB | | Hui, Shu-Ping Browse this author →KAKEN DB | | Chalfant, Charles E. Browse this author | | Parcha, Vibhu Browse this author | | Arora, Pankaj Browse this author | | Halade, Ganesh V. Browse this author |
| Keywords: | heart failure | | ischemic heart disease | | LC/MS | | myocardial infarction | | sphingosine-1-phosphate |
| Issue Date: | 3-Sep-2021 |
| Publisher: | American Physiological Society |
| Journal Title: | American journal of physiology. Heart and circulatory physiology |
| Volume: | 321 |
| Issue: | 3 |
| Start Page: | H599 |
| End Page: | H611 |
| Publisher DOI: | 10.1152/ajpheart.00314.2021 |
| PMID: | 34415189 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/86697 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
|
