A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of 1-BP (1-Benzyl-1-(11-hydroxyundecyl)piperidin-1-ium chloride)
2.2. Cell Culture and Transfection
2.3. Measurement of Ca2+ Responses in 96-Well Plates
2.4. Fluorescent Ca2+ Imaging
2.5. Immunofluorescent Staining
2.6. Mouse Models
2.7. Histological Analysis
2.8. Analysis of Motor Activities
2.9. Western Blotting
2.10. Measuring Sphk-1 mRNA Expression in Gastrocnemius Muscles
2.11. Fluorescent Measurement of Nitric Oxide (NO)
2.12. The Tension Measurement with Arterial Rings Isolated from Mice
2.13. Electrophysiology
2.14. Statistics
3. Results
3.1. Identification of Selective TRPC3/6 Inhibitors
3.2. 1-BP Specifically Suppresses TRPC3/6 Channels
3.3. A TRPC3/6 Inhibitor 1-BP Improves Blood Flow Recovery after HLI
3.4. 1-BP Preserves Myoglobin Expression in Skeletal Muscle and Walking Abilities after HLI
3.5. 1-BP Improves Blood Flow via TRPC6 Inhibition
3.6. 1-BP Promotes Arteriogenesis Independently of Hypoxia and Inflammation
3.7. 1-BP Promotes Arteriogenesis Independently of Endothelium and Preserves Endothelial Function
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Shimauchi, T.; Numaga-Tomita, T.; Kato, Y.; Morimoto, H.; Sakata, K.; Matsukane, R.; Nishimura, A.; Nishiyama, K.; Shibuta, A.; Horiuchi, Y.; et al. A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia. Cells 2022, 11, 2041. https://doi.org/10.3390/cells11132041
Shimauchi T, Numaga-Tomita T, Kato Y, Morimoto H, Sakata K, Matsukane R, Nishimura A, Nishiyama K, Shibuta A, Horiuchi Y, et al. A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia. Cells. 2022; 11(13):2041. https://doi.org/10.3390/cells11132041
Chicago/Turabian StyleShimauchi, Tsukasa, Takuro Numaga-Tomita, Yuri Kato, Hiroyuki Morimoto, Kosuke Sakata, Ryosuke Matsukane, Akiyuki Nishimura, Kazuhiro Nishiyama, Atsushi Shibuta, Yutoku Horiuchi, and et al. 2022. "A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia" Cells 11, no. 13: 2041. https://doi.org/10.3390/cells11132041