1. Academic Validation
  2. Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage

Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage

  • Cells. 2022 Sep 3;11(17):2755. doi: 10.3390/cells11172755.
Qi Cui 1 2 Yingmei Zhang 1 2 Ning Tian 1 3 Jiaxin Yang 1 2 Dongshan Ya 1 2 Wenjing Xiang 1 2 Zixian Zhou 1 2 Yanlin Jiang 4 Jungang Deng 4 Bin Yang 3 Xiaohui Lin 5 Qinghua Li 1 2 3 Rujia Liao 1 2 3
Affiliations

Affiliations

  • 1 Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 2 Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 3 Guangxi Clinical Research Center for Neurological Diseases, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 4 Department of Pharmacology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 5 Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
Abstract

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that Leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of Leptin on ICH has not been adequately explored. Moreover, Leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous Leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, Leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed Leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in Leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that Leptin boost post-ICH angiogenesis potentially through modulation of Leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, Leptin may be a lucrative option for the treatment of ICH.

Keywords

angiogenesis; intracerebral hemorrhage; leptin; neuroprotection; pericyte.

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