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The Lamb dipole is a traveling wave solution to the two-dimensional Euler equations introduced by S. A. Chaplygin (1903) and H. Lamb (1906) at the early 20th century. We prove orbital stability of this solution based on a vorticity method initiated by V. I. Arnold. Our method is a minimization of a penalized energy with multiple constraints that deduces existence and orbital stability for a family of traveling waves. As a typical case, orbital stability of the Lamb dipole is deduced by characterizing a set of minimizers as an orbit of the dipole by a uniqueness theorem in the variational setting., Comment: 41 pages

We construct traveling wave solutions to the 3d Euler equations by axisymmetric Beltrami fields with a non-constant proportionality factor. They form a vortex ring with nested invariant tori consisting of level sets of the proportionality factor., 30 pages

We prove that the Stokes semigroup is a bounded analytic semigroup on L σ ∞ of angle π / 2 for two-dimensional exterior domains. This result is an end point case of the L p -boundedness of the semigroup for p ∈ ( 1 , ∞ ) , established by Borchers and Varnhorn (1993). The proof is based on the non-existence result of bounded steady flows (the Stokes paradox) and some asymptotic formula for the net force of the Stokes resolvent.

We construct global weak solutions of the Euler equations in an infinite cylinder $\Pi=\{x\in \mathbb{R}^{3}\ |\ x_h=(x_1,x_2),\ r=|x_h, Comment: 37 pages. The title is changed from the previous version. Remarks 6.4 and new references are added

We prove that bounded Beltrami fields must be symmetric if a proportionality factor depends on 2 variables in the cylindrical coordinate and admits a regular level set diffeomorphic to a cylinder or a torus., 12 pages

We prove unique existence of local-in-time smooth solutions of the Navier–Stokes equations for initial data in $$L^{p}$$ and $$p\in [3,\infty )$$ in an infinite cylinder, subject to the Neumann boundary condition.

We prove unique existence of mild solutions on Lσ∞ for the Navier–Stokes equations in an exterior domain in Rn,n≥2, subject to the non-slip boundary condition.

This paper studies the analyticity of the Stokes semigroup in an infinite cylinder or more generally a cylindrical domain with several exits to infinity in the space \({C_{0,\sigma}}\), the \({L^\infty}\)-closure of all smooth compactly supported solenoidal vector fields. These domains are not strictly admissible in the sense of the first two authors (Abe and Giga in J Evol Equ 14:1–28, 2014). However, it is shown that these domains are still admissible which yields the analyticity in \({C_{0,\sigma}}\). A new proof based on a blow-up argument is given to derive an \({L^\infty}\)-type resolvent estimate which enables us to conclude that the analyticity angle of the Stokes semigroup in \({C_{0,\sigma}}\) is \({\pi/2}\).

We consider the two-dimensional Navier-Stokes equations subject to the Dirichlet boundary condition in a half plane for initial vorticity with finite measures. We study local well-posedness of the associated vorticity equations for measures with a small pure point part and global well-posedness for measures with a small total variation. Our construction is based on an $L^{1}$-estimate of a solution operator for the vorticity equations associated with the Stokes equations., Comment: 48 pages

We establish a blow-up rate of the Navier–Stokes equations subject to the non-slip boundary condition for a certain class of domains including bounded and exterior domains.

We study Liouville theorems for the non-stationary Stokes equations in exterior domains in $ \mathbb{R}^{n}$ under decay conditions for spatial variables. As applications, we prove that the Stokes semigroup is a bounded analytic semigroup on $L^{ \infty}_{ \sigma}$ of angle $ \pi/2$ for $n \geq 3$. We also prove large time estimates for $n=2$ with zero net force., Comment: 26 pages

We study an initial-boundary value problem of the three-dimensional Navier-Stokes equations in the exterior of a cylinder $\Pi=\{x=(x_{h}, x_3)\ |\ |x_{h} |>1\}$, subject to the slip boundary condition. We construct unique global solutions for axisymmetric initial data $u_0\in L^{3}\cap L^{2}(\Pi)$ satisfying the decay condition of the swirl component $ru^{\theta}_{0}\in L^{\infty}(\Pi)$., Comment: Final version. The title is changed from "Axisymmetric flows in an exterior domain"

This paper presents a uniqueness theorem for the Stokes equations in a half space in a space of bounded functions. The Stokes equations is well understood for decaying velocity as $|x|\to\infty$, but less known for non-decaying velocity even for a half space. This paper presents a uniqueness theorem on $L^{\infty}(\mathbb{R}_+^n)$ for unbounded velocity as $t\downarrow 0$. Under suitable sup-bounds both for velocity and pressure gradient, a uniqueness theorem for non-decaying velocity is proved.

The overexpression of certain membrane-bound receptors is a hallmark of cancer progression and it has been suggested to affect the organization, activation, recycling and down-regulation of receptor-ligand complexes in human cancer cells. Thus, comparing receptor trafficking pathways in normal vs. cancer cells requires the ability to image cells expressing dramatically different receptor expression levels. Here, we have presented a significant technical advance to the analysis and processing of images collected using intensity based Förster resonance energy transfer (FRET) confocal microscopy. An automated Image J macro was developed to select region of interests (ROI) based on intensity and statistical-based thresholds within cellular images with reduced FRET signal. Furthermore, SSMD (strictly standardized mean differences), a statistical signal-to-noise ratio (SNR) evaluation parameter, was used to validate the quality of FRET analysis, in particular of ROI database selection. The Image J ROI selection macro together with SSMD as an evaluation parameter of SNR levels, were used to investigate the endocytic recycling of Tfn-TFR complexes at nanometer range resolution in human normal vs. breast cancer cells expressing significantly different levels of endogenous TFR. Here, the FRET-based assay demonstrates that Tfn-TFR complexes in normal epithelial vs. breast cancer cells show a significantly different E% behavior during their endocytic recycling pathway. Since E% is a relative measure of distance, we propose that these changes in E% levels represent conformational changes in Tfn-TFR complexes during endocytic pathway. Thus, our results indicate that Tfn-TFR complexes undergo different conformational changes in normal vs. cancer cells, indicating that the organization of Tfn-TFR complexes at the nanometer range is significantly altered during the endocytic recycling pathway in cancer cells. In summary, improvements in the automated selection of FRET ROI datasets allowed us to detect significant changes in E% with potential biological significance in human normal vs. cancer cells.

The Stokes semigroup on a bounded domain is an analytic semigroup on spaces of bounded functions as was recently shown by the authors based on an a priori L ∞-estimate for solutions to the linear Stokes equations. In this paper, we extend our approach to exterior domains and prove that the Stokes semigroup is uniquely extendable to an analytic semigroup on spaces of bounded functions.

Summary The primary purpose of this investigation was to determine whether ApoE-/- mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE-/- mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

The analyticity of the Stokes semigroup with the Dirichlet boundary condition is established in spaces of bounded functions when the domain occupied with fluid is bounded or more generally admissible which admits a special estimate for the Helmholtz decomposition. The proof is based on a blow-up argument. This is the first proof of the analyticity in spaces of bounded functions which was left open more than thirty years.

Neuroblastomas are pediatric tumors that develop from sympathetic precursors and express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both processes are Y2R-mediated, the aim of this study was to assess Y2R as a potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK) induced by endogenous NPY, which resulted in decreased proliferation and induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts, which was associated with decreased activation of p44/42 MAPK, as well as reduced proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma-conditioned media. Consequently, the Y2R antagonist-treated xenografts had decreased vascularization and a high degree of focal fibrosis. In human neuroblastoma tissues, the expression of Y2R was observed in both tumor and endothelial cells, while NPY was predominantly expressed in neuroblastoma cells. In summary, Y2R is a promising new target for neuroblastoma therapy affecting both cancer cells and tumor vasculature.

We prove global well-posedness of the two-dimensional exterior Navier-Stokes equations for bounded initial data with a finite Dirichlet integral, subject to the non-slip boundary condition. As an application, we construct global solutions for asymptotically constant initial data and arbitrary large Reynolds numbers., Comment: 40 pages, final version

We found out that the dosimetric sensitivity limit of a radiochromic film can be much improved through use of a set of color components, e.g. red R and green G, outputs from an RGB color scanner. The two light component lights suffer a common fate, with the exception of wavelength-dependent events, having passed together along common attenuation paths. The mathematical operation of creating a ratio of the two components (R:G) is analogous to the ‘common-mode rejection’ (CMR) in electronics. In the case of the GAFCHROMIC films, HS-14 and MD-55-2, the detection limit was found to be greatly improved with optical CMR, and the lowest detectable dose attained was 20 mGy for HS-14 and 50 mGy for MD-55-2.

Radiation effects of photo-stimulated luminescence (PSL) from BaFBr:Eu 2+ used for an imaging plate have been studied with various radiation sources in these years. In situ measurements of both afterglow and PSL emission from the imaging plate have been carried out with 1 MeV He + ion beam irradiation in this report. Prompt luminescence and afterglow emission peaked at 400 nm in wavelength under and just after ion beam irradiation have been observed, and the PSL has been observed after the irradiation by the excitation with 500 or 600 nm light source. We have elucidated various characteristics of the PSL of the imaging plate by the ion beam irradiation as follows. (1) The emission just after the ion beam irradiation includes the PSL and afterglow emission. (2) The behavior of the time dependence of the PSL is different from that of the afterglow emission. Fading decay time of the PSL is longer than that of the afterglow emission. (3) The spectrum of the PSL is composed of more than four transition levels.

In this paper, we study regularizing effects of the composition operator $S(t)\mathbb{P}\partial$ for the Stokes semigroup $S(t)$ and the Helmholtz projection $\mathbb{P}$ in a space of bounded functions. We establish new a priori $L^{\infty}$-estimates of the operator $S(t)\mathbb{P}\partial$ for a certain class of domains including bounded and exterior domains. They imply unique existence of mild solutions of the Navier-Stokes equations in a space of bounded functions., 35 pages, final version

A photo-stimulated luminescent (PSL) material, BaFBr 0:85 I 0:15 :Eu 2⁄ , was irradiated by 1 and 2 MeV He ⁄ ions. Thedeterioration of PSL signals caused by heavy irradiation was found quite stable for a long time. In situ measurements ofscintillation were also made during He ⁄ ion irradiation. A broad 400 nm peak and a decreasing continuum tail wereobserved for spectra of the scintillation. An afterglow e•ect was also observed as a function of time up to 10 s afterstopping the He ⁄ ion beam. Results are discussed relating with the incomplete erasing and the self generation of PSLsignals which were reported in our previous study. O 2000 Elsevier Science B.V. All rights reserved.PACS: 78.45; 78.90Keywords: Photo-stimulated luminescence (PSL); Scintillation; Radiation deterioration; He ⁄ ions; Incomplete erasing;Self generation of PSL signals; Afterglow e•ect 1. IntroductionSince photo-stimulated luminescent (PSL) ma-terials have been developed for X-ray imaging [1],many studies have been reported on their charac-teristics and responses to various radiation irra-diations [2–5]. Besides those basic studies, excellentperformances of the PSL materials have also beenreported such as wide linearity, simplicity of PSLstatistics and high confidence of stored image in-formation in practical use [6,7].Among varieties of studies, an elucidation ofthe radiation e•ect of the material in PSL andscintillation is the main interest in this study. De-terioration of PSL signals produced by 1 and 2MeV He

Due to increasing usage of conventional perforated-wall caissons as breakwaters in relatively calm seas around Japan, we conducted a series of model experiments to develop a special perforated caisson that can withstand severe wave attacks in open seas. The caisson consists of multiple slit walls which allow harbor water exchange without increasing wave transmission, while also reducing wave reflection using a small wave chamber width compared to that of a single-slit-wall caisson.

A photo-stimulated luminescent (PSL) material, BaFBr 0.85 I 0.15 : Eu 2+ , was irradiated by 1 and 2 MeV He + ions. The radiation effects were compared with that of fission neutrons, 137 Cs and 60 Co gamma-rays. Deterioration of PSL signals was measured as a function of total fluence for ions and neutrons or dose for gamma-rays. Relative deteriorations for neutrons and gamma-rays were compared with that of 1 MeV He + ion irradiation. A self-generation of PSL signals depending on fluence and storage time was observed.

The measured bathochromic shifts of 4-aminobenzophenone (4ABP) in CF3H are explained by Onsager's reaction field theory (ORFT) if the cavity radius is the sum of Van der Waals radii of solute and solvent, while in CO2, the cavity radius is the solute's Van der Waals radius. The experimental local densities around 4ABP have been estimated and show a maximum at a reduced density of 0.5 for CF3H and 0.7 for CO2. Simulations are consistent with the high local densities found at low bulk densities and suggest possible explanations for the different radii used for CF3H and CO2.

Fluorescence lifetime imaging is playing an increasing role in drug development by providing a sensitive method to monitor drug delivery and receptor-ligand interactions. However, the wide dynamic range of fluorescence intensity emitted by ex vivo and in vivo samples presents challenges in retrieving information over the whole subject accurately and quantitatively. To overcome this challenge, we developed an active wide-field illumination (AWFI) strategy based on a spatial light modulator that acquires optimal fluorescence signals by enhancing the dynamic range, signal to noise ratio, and estimation of lifetime-based parameters. We demonstrate the ability of AWFI to estimate Forster resonance energy transfer (FRET) donor fraction from dissected organs with high accuracy (standard deviation

The Stokes equation on a domain $\Omega \subset R^n$ is well understood in the $L^p$-setting for a large class of domains including bounded and exterior domains with smooth boundaries provided $1, Comment: 22 pages, to appear in Ann. Sci. \'Ec. Norm. Sup\'er. (4)

The conjugation of anti-cancer drugs to endogenous ligands has proven to be an effective strategy to enhance their pharmacological selectivity and delivery towards neoplasic tissues. Since cell proliferation has a strong requirement for iron, cancer cells express high levels of transferrin receptors (TfnR), making its ligand, transferrin (Tfn), of great interest as a delivery agent for therapeutics. However, a critical gap exists in the ability to non-invasively determine whether drugs conjugated to Tfn are internalized into target cells in vivo. Due to the enhanced permeability and retention (EPR) effect, it remains unknown whether these Tfn-conjugated drugs are specifically internalized into cancer cells or are localized non-specifically as a result of a generalized accumulation of macromolecules near tumors. By exploiting the dimeric nature of the TfnR that binds two molecules of Tfn in close proximity, we utilized a Förster Resonance Energy Transfer (FRET) based technique that can discriminate bound and internalized Tfn from free, soluble Tfn. In order to non-invasively visualize intracellular amounts of Tfn in tumors through live animal tissues, we developed a novel near infrared (NIR) fluorescence lifetime FRET imaging technique that uses an active wide-field time gated illumination platform. In summary, we report that the NIR fluorescence lifetime FRET technique is capable of non-invasively detecting bound and internalized forms of Tfn in cancer cells and tumors within a live small animal model, and that our results are quantitatively consistent when compared to well-established intensity-based FRET microscopy methods used in in vitro experiments.

One of the challenges in anti-cancer drug delivery systems is to quantitatively discriminate non-specific receptorindependent tumor accumulation from receptor-mediated uptake into the tumor cells. To overcome this challenge, we develop a new near infrared fluorescence resonance energy transfer fluorescence lifetime imaging (NIR FRET FLIM) technique with wide-field illumination strategies to validate and characterize cellular uptake in both cancer cells and normal cells with different donor-acceptor ratios in vitro and in vivo. Our results demonstrate that NIR FRET FLIM can quantitatively distinguish receptor-bound from unbound donor in live animals with high sensitivity and high accuracy. Thus, it has a great potential for the quantitative detection of targeted delivery systems for diagnostic and therapeutic use.

We previously reported that the sympathetic neurotransmitter neuropeptide Y (NPY) is potently angiogenic, primarily through its Y2 receptor, and that endogenous NPY is crucial for capillary angiogenesis in rodent hindlimb ischemia. Here we sought to identify the source of NPY responsible for revascularization and its mechanisms of action. At d 3, NPY−/− mice demonstrated delayed recovery of blood flow and limb function, consistent with impaired collateral conductance, while ischemic capillary angiogenesis was reduced (∼70%) at d 14. This biphasic temporal response was confirmed by 2 peaks of NPY activation in rats: a transient early increase in neuronally derived plasma NPY and increase in platelet NPY during late-phase recovery. Compared to NPY-null platelets, collagen-activated NPY-rich platelets were more mitogenic (∼2-fold vs. ∼1.6-fold increase) for human microvascular endothelial cells, and Y2/Y5 receptor antagonists ablated this difference in proliferation. In NPY+/+ mice, ischemic angiogenesis was prevented by platelet depletion and then restored by transfusion of platelets from NPY+/+ mice, but not NPY−/− mice. In thrombocytopenic NPY−/− mice, transfusion of wild-type platelets fully restored ischemia-induced angiogenesis. These findings suggest that neuronally derived NPY accelerates the early response to femoral artery ligation by promoting collateral conductance, while platelet-derived NPY is critical for sustained capillary angiogenesis.—Tilan, J. U., Everhart, L. M., Abe, K., Kuo-Bonde, L., Chalothorn, D., Kitlinska, J., Burnett, M. S., Epstein, S. E., Faber, J. E., Zukowska, Z. Platelet neuropeptide Y is critical for ischemic revascularization in mice.

One of the key challenges in anti-cancer drug validation is to quantitatively discriminate in vivo non-specific receptor-independent tumor accumulation from receptor-mediated uptake into the tumor cells. To overcome this challenge, we develop a new near-infrared Forster resonance energy transfer fluorescence lifetime imaging (NIR FRET FLIM) technique. We apply herein this novel approach to monitor and characterize cellular uptake in both cancer cells and normal cells in vitro and in vivo. Our results demonstrate that NIR FRET FLIM can quantitatively distinguish receptor-bound from unbound donor in live animals with high sensitivity and high accuracy. Thus, it has a great potential for the quantitative detection of targeted delivery systems for diagnostic and therapeutic use.

Wide-field fluorescence lifetime imaging allows for fast imaging of large sample at the cost of limited sensitivity to weak fluorescence signals. To overcome this limitation, we develop an active illumination strategy that optimizes the spatial parameters of the illumination in order to acquire optimal wide-field fluorescence signals even in the presence of large fluorophore concentration distributions. We validate the sensitivity gain of our approach in a multi-well plate setting with fluorophore concentrations ranging >2 orders of magnitude. We report the ability of our method to retrieve accurately the lifetime over this concentration range based on optimized wide-field data. Our results demonstrate that an active wide-field illumination can improve the signal-to-noise ratio and weak-signal sensitivity for enhanced accuracy of fluorescence decay curve fitting and lifetime estimation at high acquisition speed.

We developed an active illumination strategy to acquire fluorescence signals over large fluorophore concentration distributions. It can improve the SNR and weak-signal sensitivity for enhanced accuracy of lifetime estimation at high acquisition speed.

A novel near infrared FRET fluorescence lifetime imaging technique with wide-field illumination strategies was developed to validate and characterize cellular uptake of transferrin in both cancer cells and normal cells in vitro and in vivo.

Some members of the transient receptor potential (TRP) channel superfamily have proved to be essential in maintaining adequate ion homeostasis, signaling, and membrane trafficking in the endosomal pathway. The unique properties of the TRP channels confer cells the ability to integrate cytosolic and intraluminal stimuli and allow maintained and regulated release of Ca2+ from endosomes and lysosomes.

Neuropeptide Y (NPY) is a central neuromodulator and peripheral sympathetic neurotransmitter that also has important regulatory roles in cardiovascular, neuroendocrine, immune and metabolic functions during stress. Focusing on the peripheral actions of the peptide in rodent models, we summarize recent studies from our laboratory demonstrating that stress-induced release of NPY mediates accelerated atherosclerosis/restenosis, obesity and metabolic-like syndrome, particularly when combined with a high fat, high sugar diet. In this review, we propose mechanisms of NPY's actions, its receptors and cellular substrates that increase the risk for cardiovascular and metabolic diseases when chronic stress is associated with pre-existing vascular injury and/or states of hypernutrition.

Although rare, interneurons are pivotal in governing striatal output by extensive axonal arborizations synapsing on medium spiny neurons. Using a genetically modified mouse strain in which a green fluorescent protein (GFP) is driven to be expressed under control of the neuropeptide Y (NPY) promoter, we identified NPY interneurons and compared them with striatal principal neurons. We found that the bacteria artificial chromosome (BAC)- npy mouse expresses GFP with high fidelity in the striatum to the endogenous expression of NPY. Patch-clamp analysis from NPY neurons showed a heterogeneous population of striatal interneurons. In the majority of cells, we observed spontaneous firing of action potentials in extracellular recordings. On membrane rupture, most NPY interneurons could be classified as low-threshold spiking interneurons and had high-input resistance. Voltage-clamp recordings showed that both GABA and glutamate gated ion channels mediate synaptic inputs onto these striatal interneurons. AMPA receptor–mediated spontaneous excitatory postsynaptic currents (sEPSCs) were small in amplitude and infrequent in NPY neurons. Evoked EPSCs did not show short-term plasticity but some rectification. Evoked N-methyl-d-aspartate (NMDA) EPSCs had fast decay kinetics and were poorly sensitive to an NR2B subunit containing NMDA receptor blocker. Spontaneous inhibitory postsynaptic currents (sIPSCs) were mediated by GABAA receptors and were quite similar among all striatal neurons studied. On the contrary, evoked IPSCs decayed faster in NPY neurons than in other striatal neurons. These data report for the first time specific properties of synaptic transmission to NPY striatal interneurons.

General anesthetics (GAs) have transformed surgery through their actions to depress the central nervous system and blunt the perception of surgical insults. Counterintuitively, many of these agents activate peripheral nociceptive neurons. However, the underlying mechanisms and significance of these effects have not been explored. Here, we show that clinical concentrations of noxious i.v. and inhalation GAs excite sensory neurons by selectively activating TRPA1, a key ion channel in the pain pathway. Further, these GAs induce pain-related responses in mice that are abolished in TRPA1-null animals. Significantly, TRPA1-dependent neurogenic inflammation is greater in mice anesthetized with pungent compared with nonpungent anesthetics. Thus, our results show that TRPA1 is essential for sensing noxious GAs. The pronociceptive effects of GAs combined with surgical tissue damage could lead to a paradoxical increase in postoperative pain and inflammation.

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors (Y1-Y6) and exerts a variety of cardiovascular effects. Originally known as a vasoconstrictor acting on Y1 receptors, NPY is also a potent angiogenic factor as well as a powerful stimulator of vascular smooth muscle proliferation and atherogenesis in vitro and in vivo. These two types of vascular remodeling are predominantly mediated by Y2/Y5 and Y1 receptors respectively, but evidence suggests that all receptors are activated in both conditions. A strategy to inhibit neointima formation and atherosclerotic lesions without impairing ischemic angiogenesis and collateral vessel formation has been a major challenge to overcome. Studies in rodents show that Y1 receptor antagonist inhibits angioplasty-induced atherosclerotic-like vascular remodeling, without affecting ischemic revascularization. Conversely, Y2 receptor activation appears to be sufficient to stimulate angiogenesis in various animal models. Thus, the use of selective receptor agonists to promote angiogenesis through the Y2 receptor while antagonizing the pro-atherosclerotic and pro-stenotic effects with Y1 receptor-selective antagonists may help to successfully treat vascular remodeling in cardiovascular diseases.