Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles

Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are protective against sepsis via regulating vascular reactivity and permeabil...

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Veröffentlicht in:Military Medical Research 2023-03, Vol.10 (1), p.13-13, Article 13
Hauptverfasser: Zhang, Zi-Sen, Liu, Yi-Yan, He, Shuang-Shuang, Bao, Dai-Qin, Wang, Hong-Chen, Zhang, Jie, Peng, Xiao-Yong, Zang, Jia-Tao, Zhu, Yu, Wu, Yue, Li, Qing-Hui, Li, Tao, Liu, Liang-Ming
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Sprache:eng
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Zusammenfassung:Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are protective against sepsis via regulating vascular reactivity and permeability. We conducted a series of in vivo experiments using wild-type (WT), platelet-derived growth factor receptor beta (PDGFR-β)-Cre + mT/mG transgenic mice and Tie2-Cre + Cx43 mice to examine the relative contribution of pericytes in sepsis, either induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. In a separate set of experiments with Sprague-Dawley (SD) rats, pericytes were depleted using CP-673451, a selective PDGFR-β inhibitor, at a dosage of 40 mg/(kg·d) for 7 consecutive days. Cultured pericytes, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were used for mechanistic investigations. The effects of pericytes and pericyte-derived microvesicles (PCMVs) and candidate miRNAs on vascular reactivity and barrier function were also examined. CLP and LPS induced severe injury/loss of pericytes, vascular hyporeactivity and leakage (P 
ISSN:2054-9369
2095-7467
2054-9369
DOI:10.1186/s40779-023-00442-2