Salidroside facilitates therapeutic angiogenesis in diabetic hindlimb ischemia by inhibiting ferroptosis

Yicheng Wang; Jingxuan Han; Lailiu Luo; Vivi Kasim; Shourong Wu

doi:10.1016/j.biopha.2023.114245

Salidroside facilitates therapeutic angiogenesis in diabetic hindlimb ischemia by inhibiting ferroptosis

Biomed Pharmacother. 2023 Mar:159:114245. doi: 10.1016/j.biopha.2023.114245. Epub 2023 Jan 12.

Authors

Yicheng Wang¹, Jingxuan Han¹, Lailiu Luo¹, Vivi Kasim², Shourong Wu³

Affiliations

¹ Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China; The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China.
² Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China; The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China; State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address: vivikasim@cqu.edu.cn.
³ Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China; The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China; State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address: shourongwu@cqu.edu.cn.

PMID: 36638593
DOI: 10.1016/j.biopha.2023.114245

Abstract

Hindlimb ischemia (HLI), in which blood perfusion to the hindlimb is obstructed, is one of the major complications of diabetes. Skeletal muscle cells are crucial for revascularization as they can secrete various angiogenic factors; however, hyperglycemia impairs their viability and subsequently their angiogenic potential. Salidroside can promote skeletal muscle cell viability under hyperglycemia; however, the molecular mechanism is still poorly understood. Here we revealed that salidroside could suppress hyperglycemia-induced ferroptosis in skeletal muscle cells by promoting GPX4 expression, thereby restoring their viability and paracrine functions. These in turn promoted the proliferation and migration potentials of blood vessel-forming cells. Furthermore, we showed that salidroside/GPX4-mediated ferroptosis inhibition is crucial for promoting angiogenesis and blood perfusion recovery in diabetic HLI mice. Together, we reveal a novel molecular mechanism of salidroside in enhancing skeletal muscle cells-mediated revascularization and blood perfusion recovery in diabetic HLI mice, further highlighting it as a potential compound for treating diabetic HLI.

Keywords: Diabetic HLI; Ferroptosis; Salidroside; Skeletal muscle cells; Therapeutic angiogenesis.

MeSH terms

Animals
Diabetes Mellitus*
Disease Models, Animal
Ferroptosis*
Hindlimb / metabolism
Hyperglycemia*
Ischemia / metabolism
Mice
Mice, Inbred C57BL
Muscle, Skeletal / metabolism
Neovascularization, Physiologic

Substances

rhodioloside