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Cells
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10.3390/cells10040795
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Article

Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study

by
Anaïs Moyon
1,2,3,
Philippe Garrigue
1,2,3,
Laure Balasse
1,2,
Samantha Fernandez
2,
Pauline Brige
2,4,
Ahlem Bouhlel
1,2,
Guillaume Hache
1,2,
Françoise Dignat-George
1,5,
David Taïeb
2,6,7 and
Benjamin Guillet
1,2,3,*
1
Aix Marseille University, INSERM 1263, INRAE 1260, C2VN, 13005 Marseille, France
2
Aix-Marseille University, CNRS 2012, CERIMED, 13005 Marseille, France
3
APHM, Service de Radiopharmacie, 13005 Marseille, France
4
Aix-Marseille University, UR4264, LIIE, 13005 Marseille, France
5
APHM, Service d’Hématologie, Hôpital Conception, 13005 Marseille, France
6
Aix-Marseille University, INSERM 1068, CNRS 7258, CRCM, 13008 Marseille, France
7
APHM, Service de Médecine Nucléaire, 13005 Marseille, France
*
Author to whom correspondence should be addressed.
Cells 2021, 10(4), 795; https://doi.org/10.3390/cells10040795
Submission received: 22 February 2021 / Revised: 26 March 2021 / Accepted: 29 March 2021 / Published: 2 April 2021
(This article belongs to the Collection Molecular and Cellular Mechanisms of Ischemia-Reperfusion Injury and Protective Strategies)
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Abstract

Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([68Ga]Ga-RGD2) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.
Keywords: succinate; RGD; gallium-68; PET; angiogenesis; vascularization; GPR91 succinate; RGD; gallium-68; PET; angiogenesis; vascularization; GPR91
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MDPI and ACS Style

Moyon, A.; Garrigue, P.; Balasse, L.; Fernandez, S.; Brige, P.; Bouhlel, A.; Hache, G.; Dignat-George, F.; Taïeb, D.; Guillet, B. Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study. Cells 2021, 10, 795. https://doi.org/10.3390/cells10040795

AMA Style

Moyon A, Garrigue P, Balasse L, Fernandez S, Brige P, Bouhlel A, Hache G, Dignat-George F, Taïeb D, Guillet B. Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study. Cells. 2021; 10(4):795. https://doi.org/10.3390/cells10040795

Chicago/Turabian Style

Moyon, Anaïs, Philippe Garrigue, Laure Balasse, Samantha Fernandez, Pauline Brige, Ahlem Bouhlel, Guillaume Hache, Françoise Dignat-George, David Taïeb, and Benjamin Guillet. 2021. "Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study" Cells 10, no. 4: 795. https://doi.org/10.3390/cells10040795

APA Style

Moyon, A., Garrigue, P., Balasse, L., Fernandez, S., Brige, P., Bouhlel, A., Hache, G., Dignat-George, F., Taïeb, D., & Guillet, B. (2021). Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study. Cells, 10(4), 795. https://doi.org/10.3390/cells10040795

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