Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage

Qi Cui; Yingmei Zhang; Ning Tian; Jiaxin Yang; Dongshan Ya; Wenjing Xiang; Zixian Zhou; Yanlin Jiang; Jungang Deng; Bin Yang; Xiaohui Lin; Qinghua Li; Rujia Liao

doi:10.3390/cells11172755

Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage

Cells. 2022 Sep 3;11(17):2755. doi: 10.3390/cells11172755.

Authors

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 Jiang⁴, Jungang Deng⁴, Bin Yang³, Xiaohui Lin⁵, Qinghua Li^{1

2

3}, Rujia Liao^{1

2

3}

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.

MeSH terms

Animals
Cerebral Hemorrhage* / metabolism
Endothelial Cells / metabolism
Humans
Leptin* / metabolism
Leptin* / pharmacology
Mice
Neovascularization, Physiologic*
Pericytes* / metabolism
STAT3 Transcription Factor / metabolism

Substances

Leptin
STAT3 Transcription Factor
STAT3 protein, human

Grants and funding

This work was supported by Grant Number 2020GXNSFAA259036 (to Rujia Liao) from the Fund of the Guangxi Natural Science Foundation, and the Guangxi Science and Technology Project (Grant Number Guike AD17129015 for Qinghua Li), and the Fund of Guangxi Research and Innovation Base for Basic and Clinical Application of Nerve Injury and Repair Project (Grant Number Guike ZY21195042 for Qinghua Li). Partial financial support was received from the Innovation Projects of Guangxi Graduate Education (YCSW2021246 for Zixian Zhou and YCSW2021254 for Wenjing Xiang). Partial financial support was received from the Plan Project of Guilin Scientific Research and Technology Development (2020011204-9 for Jungang Deng).