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Angiogenesis after ischemic stroke

Acta Pharmacologica Sinica volume 44, pages 1305–1321 (2023)Cite this article

Abstract

Owing to its high disability and mortality rates, stroke has been the second leading cause of death worldwide. Since the pathological mechanisms of stroke are not fully understood, there are few clinical treatment strategies available with an exception of tissue plasminogen activator (tPA), the only FDA-approved drug for the treatment of ischemic stroke. Angiogenesis is an important protective mechanism that promotes neural regeneration and functional recovery during the pathophysiological process of stroke. Thus, inducing angiogenesis in the peri-infarct area could effectively improve hemodynamics, and promote vascular remodeling and recovery of neurovascular function after ischemic stroke. In this review, we summarize the cellular and molecular mechanisms affecting angiogenesis after cerebral ischemia registered in PubMed, and provide pro-angiogenic strategies for exploring the treatment of ischemic stroke, including endothelial progenitor cells, mesenchymal stem cells, growth factors, cytokines, non-coding RNAs, etc.

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Fig. 1: Schematics of key steps in angiogenesis after ischemic stroke.
Fig. 2: Major stem cell therapies and its mechanisms for ischemic stroke.
Fig. 3: Major factors and signaling pathways of angiogenesis after cerebral ischemia. Ischemia or hypoxia resulting from cerebral ischemia increased VEGF expression by upregulating HIF-1α and 15-LO-1/15-HETE systems, and subsequently VEGF promoted pericyte coverage of ECs by increasing N-cadherin expression on brain capillaries.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China Major Project (No. 81730098), the Medical Innovation Major Project (No. 16CXZ009), and the Shanghai Science and Technology Commission Project (No. 21140901000).

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  1. Department of Pharmacology, Second Military Medical University / Naval Medical University, Shanghai, 200433, China

    Jie Fang, Zhi Wang & Chao-yu Miao

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Fang, J., Wang, Z. & Miao, Cy. Angiogenesis after ischemic stroke. Acta Pharmacol Sin 44, 1305–1321 (2023). https://doi.org/10.1038/s41401-023-01061-2

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