Paracrine control of vascular innervation in health and disease

Storkebaum, Erik; Carmeliet, Peter

doi:10.1111/j.1748-1716.2011.02333.x

Cited by 31 publications

(36 citation statements)

References 315 publications

(301 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many have been discussed at length, including nitric oxide (NO • ), prostacyclin, heparins, and membrane-bound molecules such as ephrins. 6 In this review, we will focus on the vascular production and conse-in the vasculature.…”

Section: Nitric Oxide (No • )mentioning

confidence: 99%

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –

Craige

Kant

Keaney

2015

Circ J

View full text Add to dashboard Cite

Endothelial function is largely dictated by its ability to rapidly sense environmental cues and adapt to these stimuli through changes in vascular tone, inflammation/immune recruitment, and angiogenesis. When any one of these abilities is compromised, the endothelium becomes dysfunctional, which ultimately leads to disease. Reactive oxygen species (ROS) have been established at the forefront of endothelial dysfunction; however, more careful examination has demonstrated that ROS are fundamental to each of the sensing/signaling roles of the endothelium. The purpose of this review is to document endothelial ROS production in both disease and physiological adaptation. Through understanding new endothelial signaling paradigms, we will gain insight into more targeted therapeutic strategies for vascular diseases. 1146CRAIGE SM et al.function is not new. It was noted more than 60 years ago that antioxidant supplementation of model organisms improved maximum lifespan. From this observation Denman Harman developed the "oxidative theory of aging", which suggests ROS-mediated damage to macromolecules (eg, DNA, RNA, protein) over one's lifetime leads to the manifestations of aging. 18 Many other conditions are known to involve oxidative stress, broadly defined as an excess of oxidants over the species required to detoxify them. 19 These earlier concepts concerning ROS biology typically focused on their potential for damaging cellular components. Because oxygen is a ubiquitous component of higher order biologic systems, it is not surprising that ROS can be generated by diverse cellular processes such as mitochondrial electron transfer, drug detoxification by cytochrome p450s, uncoupling of eNOS, and an array of oxidase enzymes such as xanthine oxidase and NADPH oxidases, among others. The most facile ROS produced in biological systems is O2 •− , as it requires only a single-electron reduction of molecular oxygen (Figure 1). The most common fates for O2 •− (based upon rate constants) are dismutation to H2O2 or its reaction with NO • to form ONOO − . In specific circumstances that involve accessible redox-active metal ions (which are rare in vivo), O2 •− can also undergo sequential reduction.In addition to their role in mediating cellular damage (typically at high concentrations), low level ROS production has been implicated in cellular signaling. 20 In this context it is important to consider the specific properties of distinct ROS that may dictate the types of signaling to which they are best suited. Superoxide has been implicated in signaling, but it is a charged species that cannot cross membranes, suggesting it is best suited for very local signal propagation. Moreover, O2 •− is subject to both spontaneous (rate constant=8×10 4 M −1 s −1 ), and enzymatic (rate constant=2×10 9 M −1 s −1 ) dismutation to H2O2. Given that most cells and cellular compartments have abundantly available SOD, one must consider that O2 •− is likely to have a very short half-life in biological systems. Conversely, H2O2 is a relatively stable 2-ele...

show abstract

Section: Nitric Oxide (No • )mentioning

confidence: 99%

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –

Craige

Kant

Keaney

2015

Circ J

View full text Add to dashboard Cite

show abstract

“…In many organs, vascular and neural structures are closely aligned (Bearden and Segal, 2005;Correa and Segal, 2012;Mukouyama et al, 2005;Mukouyama et al, 2002;Stubbs et al, 2009), reflecting their interdependent existence (Quaegebeur et al, 2011) and synchronized function (Storkebaum and Carmeliet, 2011). Defining how these vascular and neural elements are patterned is important for a full understanding of organ formation, as well as pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

et al. 2014

View full text Add to dashboard Cite

Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGFinduced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the isletderived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers.

show abstract

“…Maintenance of arterial neurovascular junctions requires vascular endothelial growth factor (6). Innervation density differs between arteries, with large elastic arteries such as the aorta being poorly innervated and small resistance arteries such as the mesenteric and cutaneous arteries showing very dense innervation (7,8). Sympathetic varicosities induce vasoconstrictor responses in these resistance arteries, thereby reducing peripheral tissue perfusion in environmental stress situations (7,9).…”

Section: Introductionmentioning

confidence: 99%

Netrin-1 controls sympathetic arterial innervation

Brunet¹,

Gordon²,

Han³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

show abstract

Paracrine control of vascular innervation in health and disease

Cited by 31 publications

References 315 publications

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –

Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

Netrin-1 controls sympathetic arterial innervation

Contact Info

Product

Resources

About

Paracrine control of vascular innervation in health and disease

Cited by 31 publications

References 315 publications

Reactive Oxygen Species in Endothelial Function – From Disease to Adaptation –

Reactive Oxygen Species in Endothelial Function – From Disease to Adaptation –

Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

Netrin-1 controls sympathetic arterial innervation

Contact Info

Product

Resources

About

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –

Reactive Oxygen Species in Endothelial Function　– From Disease to Adaptation –