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

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.

Succinate at the Crossroad of Metabolism and Angiogenesis: Roles of SDH, HIF1α and SUCNR1

“…Furthermore, targeting SDH prevented succinate accumulation and inhibited angiogenesis in rheumatoid arthritis [ 60 ]. In addition, succinate injection promoted earlier angiogenesis after acute peripheral ischemia in mice, inducing more effective revascularization with prolonged response [ 146 ]. Evidence also supported that succinate/SUCNR1 enhanced post-hypoxia/ischemia vascularization and reduced infarct size in a mouse model of newborn hypoxia/ischemia brain injury acting through prostaglandin E 2 –prostaglandin E receptor 4 to govern expression of major angiogenic factors.…”