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Pericytes are contractile vascular mural cells overlying capillary endothelium, and they have been implicated in a variety of functions including regulation of cerebral blood flow. Recent work has suggested that both in vivo and ex vivo, ischaemia causes pericytes to constrict and die, which has implications for microvascular reperfusion. Assessing pericyte contractility in tissue slices and in vivo is technically challenging, while in vitro techniques remain unreliable. Here, we used isolated cultures of human brain vascular pericytes to examine their contractile potential in vitro using the iCelligence electrical impedance system. Contraction was induced using the vasoactive peptide endothelin-1, and relaxation was demonstrated using adenosine and sodium nitroprusside. Endothelin-1 treatment also resulted in increased proliferation, which we were able to monitor in the same cell population from which we recorded contractile responses. Finally, the observation of pericyte contraction in stroke was reproduced using chemical ischaemia, which caused a profound and irreversible contraction clearly preceding cell death. These data demonstrate that isolated pericytes retain a contractile phenotype in vitro, and that it is possible to quantify this contraction using real-time electrical impedance recordings, providing a significant new platform for assessing the effects of vasoactive and vasculoprotective compounds on pericyte contractility.

Original publication

DOI

10.1177/0271678X16659495

Type

Journal article

Journal

J Cereb Blood Flow Metab

Publication Date

06/2017

Volume

37

Pages

2013 - 2024

Keywords

Human brain vascular pericytes, contractility, iCelligence, ischemia, Brain, Brain Ischemia, Cell Culture Techniques, Cell Proliferation, Cells, Cultured, Electric Impedance, Endothelin-1, Endothelium, Vascular, High-Throughput Screening Assays, Humans, Muscle Contraction, Muscle, Smooth, Vascular, Pericytes, Vasoconstriction, Vasodilation