The Myoendothelial Junction: Connections That Deliver the Message

Straub, Adam C.; Zeigler, Angela C.; Isakson, Brant E.

doi:10.1152/physiol.00042.2013

Cited by 74 publications

(70 citation statements)

References 67 publications

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“…8–10 The MEJs are anatomical hallmarks where primarily endothelium (depending on vascular bed) breaks through the internal elastic lamina (IEL) and comes into close apposition with the overlying smooth muscle cells, forming gap junctions for direct cell-cell communication (reviewed in 11 ). The MEJs are found in resistance arteries down to terminal arterioles, with little to no MEJs identified in conduit arteries.…”

Section: Introductionmentioning

confidence: 99%

“…The MEJs are found in resistance arteries down to terminal arterioles, with little to no MEJs identified in conduit arteries. 11 These cellular structures provide a distinct microenvironment at the interface between smooth muscle and endothelium where a number of proteins have been shown to be localized and enriched to influence heterocellular cross talk in the arterial blood vessel wall. Indeed, we have found that eNOS is polarized across vascular beds at MEJs 7 , and more recently have demonstrated that endothelial cells in resistance arteries synthesize and express hemoglobin α (Hb α) which co-localizes with eNOS at MEJs where it functions to regulate NO diffusion to vascular smooth muscle during α 1 -adrenergic-dependent vasoconstriction 10 .…”

Section: Introductionmentioning

confidence: 99%

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Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction

Straub

Butcher

Billaud

et al. 2014

ATVB

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107

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Objective Hb α and eNOS form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates NO signaling, vascular reactivity and blood pressure using a mimetic peptide of Hb α to disrupt this interaction. Approach and Results In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Utilizing in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. FITC-labeling of Hb α X revealed localization to holes in the internal elastic lamina (i.e., myoendothelial junctions). To test the functional effects of Hb α X, we measured cGMP and vascular reactivity. Our results reveal augmented cGMP production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X which caused a significant decrease in blood pressure; injection of Hb α X into eNOS−/− mice had no effect. Conclusion These results identify a novel sequence on Hb α that is important for Hb α / eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction

Straub

Butcher

Billaud

et al. 2014

ATVB

Self Cite

107

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show abstract

“…Over the next 50 years, research into the functional roles of these projections revealed their importance in second messenger communication and electrical signaling within the vascular wall. MEJs tend to have a greater presence in arteries with a smaller luminal size [2, 3], which allows these vessels a faster endothelial response to second messengers originating in the smooth muscle [4] by providing a platform for the organization and localization of signaling proteins [5]. …”

Section: Introductionmentioning

confidence: 99%

Compartmentalized nitric oxide signaling in the resistance vasculature

Mutchler¹,

Straub

2015

Nitric Oxide

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Nitric oxide (NO) was first described as a bioactive molecule through its ability to stimulate soluble guanylate cyclase, but the revelation that NO was the endothelium derived relaxation factor drove the field to its modern state. The wealth of research conducted over the past 30 years has provided us with a picture of how diverse NO signaling can be within the vascular wall, going beyond simple vasodilation to include such roles as signaling through protein S-nitrosation. This expanded view of NO’s actions requires highly regulated and compartmentalized production. Importantly, resistance arteries house multiple proteins involved in the production and transduction of NO allowing for efficient movement of the molecule to regulate vascular tone and reactivity. In this review, we focus on the many mechanisms regulating NO production and signaling action in the vascular wall, with a focus on the control of endothelial nitric oxide synthase (eNOS), the enzyme responsible for synthesizing most of the NO within these confines. We also explore how cross talk between the endothelium and smooth muscle in the microcirculation can modulate NO signaling, illustrating that this one small molecule has the capability to produce a plethora of responses.

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“…(102) Under 100nm in diameter, their distribution is heterogeneous throughout the vasculature, with a higher concentration located in smaller caliber arteries as opposed to the larger proximal arteries. (103) To date, only Cx37, Cx40, and Cx43 have been identified within MEPs, with Cx40 shown to be involved in endothelial-derived hyperpolarization (EDH)-mediated vasodilation.…”

Section: Regional Vessel Communicationmentioning

confidence: 99%

Communication Is Key: Mechanisms of Intercellular Signaling in Vasodilation

Freed¹,

Gutterman

2017

Journal of Cardiovascular Pharmacology

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Thirty years ago Robert F. Furchgott concluded that nitric oxide, a compound traditionally known to be a toxic component of fuel exhaust, is in fact released from the endothelium, and in a paracrine fashion, induces relaxation of underlying vascular smooth muscle resulting in vasodilation. This discovery has helped pave the way for a more thorough understanding of vascular inter- and intracellular communication that supports the process of regulating regional perfusion to match local tissue oxygen demand. Vasoregulation is not only controlled by endothelial release of a diverse class of vasoactive compounds such as nitric oxide, arachidonic acid metabolites, and reactive oxygen species, but also via physical forces on the vascular wall and through electrotonic conduction through gap junctions. Although the endothelium is a critical source of vasoactive compounds, paracrine mediators can also be released from surrounding parenchyma such as perivascular fat, myocardium, and cells in the arterial adventitia to exert either local or remote vasomotor effects. The focus of this review will highlight the various means by which intercellular communication contributes to mechanisms of vasodilation. Paracrine signaling and parenchymal influences will be reviewed as well as regional vessel communication via gap junctions, connexons, and myoendothelial feedback. More recent modes of communication such as vesicular and microRNA signaling will also be discussed.

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The Myoendothelial Junction: Connections That Deliver the Message

Cited by 74 publications

References 67 publications

Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction

Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction

Compartmentalized nitric oxide signaling in the resistance vasculature

Communication Is Key: Mechanisms of Intercellular Signaling in Vasodilation

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