Biologically Active Lipids in Vascular Biology

Upchurch, Clint; Leitinger, Norbert

doi:10.1007/978-3-030-12270-6_9

Cited by 2 publications

(1 citation statement)

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“…These vessels are covered by cells expressing high levels of α-smooth muscle actin (α-SMA) with ovoid cell bodies and multiple broad processes that almost completely ensheathe the underlying vessel (Grant et al, 2019;Figure 3A). Given that the identity of these cells is unresolved, and that they have been referred to as both pericytes (Peppiatt et al, 2006;Hall et al, 2014;Attwell et al, 2016;Grant et al, 2019) and SMCs (Hill et al, 2015;Grutzendler and Nedergaard, 2019), we refer to these cells here as "contractile mural cells" and to the segments of the vasculature Wroblewska et al, 1998;Harrison et al, 2008;Palazzo et al, Praticò and Dogné, 2005;Kaczynski et al, 2016;Longden et al, 2019;Upchurch and Leitinger, 2019;Ozen et al, Shima et al, 2007;Cortijo et al, 2012;Sugimura et al, 2012 Frizzled receptors…”

Section: Mural Cell Properties Transition Gradually With Increasing Bmentioning

confidence: 99%

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Hariharan

Weir

Robertson

et al. 2020

Front. Cell. Neurosci.

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Brain pericytes reside on the abluminal surface of capillaries, and their processes cover ~90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for Gs-coupled GPCRs and ATP-sensitive potassium (KATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and Gq, Gi/o, and G12/13 signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease.

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