Epigenetic landscape reveals MECOM as an endothelial lineage regulator.

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator.

Spatially confined growth of carbon nanotubes in the pore channels of microporous ceramic supports with improved filtration efficiency.

Carbon nanotubes (CNTs) with high degrees of uniformity, orientation and controlled dimensions on porous supports are highly desirable for various applications such as separation of O/W emulsions and air purification. In this work, CNTs were fabricated on silicon carbide (SiC) porous supports with different porosities and pore sizes by chemical vapor deposition (CVD). The growth processes of CNTs on the surface and in the pore channels of the SiC support were studied in detail. Based on microstructural characterization by SEM, Raman spectroscopy and TEM, it was found that these CNTs grown in the pore channels of SiC supports had a higher degree of orientation and purity than those grown on the surface due to the spatially confined effect. The growth processes of various types of CNTs on the microporous supports were proposed, which were further verified by CNTs with different steric configurations (S-CNTs and VACNTs) and on Al2O3 porous supports. Moreover, the contribution of CNTs in the pore channels to the filtration efficiency was demonstrated in oil-water emulsion separation and particle removal in air. This work provides significant guidance for the preparation and filtration application of CNTs on porous materials.

3D spray-coated gradient profile ceramic membranes enables improved filtration performance in aerobic submerged membrane bioreactor.

Rational design of cross-sectional microstructure in ceramic membranes has shown to improve membrane filtration efficacy without affecting rejection performance. In this work, we adopted 3D spray-coating technique to generate multi-layered membrane layers on macro-porous flat-sheet ceramic supports. The thickness of each layer was controlled by spray-coating cycles, and a gradient membrane layer was rationalized by successively coating three ceramic slurries containing alumina powders of gradually refined particle sizes, followed by co-sintering. Gradient membrane layers on both sides of the various sized flat-sheet ceramic supports were fabricated. Compared to the non-gradient counterpart, the gradient membranes showed both higher pure water flux (at the same TMP) and lower membrane resistance, which clearly evidenced the benefits of gradient profile in the membrane layer. Further, their performance in aerobic membrane bioreactors (AeMBR) was comparably studied for the first time. The treatment performance was not significantly affected by the types of membranes used, while the gradient membrane showed better filtration performance (i.e., a slower rise in TMP). Although the fouling mechanisms were revealed to be similar, the fouling layer in the gradient membrane was composed of a higher percentage of smaller foulants compared to that of the non-gradient counterpart. The observed differences were closely correlated to the larger internal pore structure in the gradient membrane. The present work provides a feasible 3D spray-coating technique for the fabrication of gradient flat-sheet ceramic membranes, and clarifies the benefits in AeMBR for domestic wastewater treatment.

Silicon carbide microfiltration membranes for oil-water separation: Pore structure-dependent wettability matters.

Both the pore size and surface properties of silicon carbide (SiC) membranes are demonstrated to significantly affect their separation efficiency when used for oily water treatment. However, the potential influences of open porosity together with the pore size of SiC membranes on their surface properties and oil-water separation performance have rarely been investigated. In this work, porous SiC ceramic membranes with tunable open porosity and pore size were purposely prepared and selected to systematically study the effect of pore structure-dependent wettability on the oil-water separation performance. The measured pure water flux of selected membranes as a function of open porosity (34-48%) and pore size (0.43-0.67 µm) was well-fitted by using a modified H-P equation. Interestingly, the hydrophilicity of SiC membranes was improved with the increase in open porosity and pore size, as evidenced by the gradually decreased dynamic water contact angle and underwater adhesion of oil droplets. Further, the open porosity of SiC membranes was found to contribute more to the improved surface wettability. As a result, the stable flux of SiC membranes in oil-in-water (O/W) emulsions was increased by 24% with the increased open porosity while the oil rejection rate remained above 90%. This work quantitatively reveals the contributions of the pore structure to the surface wettability of ceramic membranes, and thus provides an effective pathway to improve their performance in oil-water separation.

Black Phosphorus@Ti3C2Tx MXene Composites with Engineered Chemical Bonds for Commercial-Level Capacitive Energy Storage.

Electrolyte-accessibly porous yet densely packed MXene composite electrodes with high ion-accessible surface and rapid ion transport rate have shown exceptional promise for high-volumetric-performance supercapacitors (SCs), but they are largely limited by the insufficient rate capability and poor electrochemical cyclability, in association with the instability in mechanical robustness of the porous network structures. Taking advantage of chemical bonding design, herein a black phosphorus (BP)@MXene compact film of 3D porous network structure is successfully made by in situ growth of BP nanoparticles on crumbled MXene flakes. The strong interfacial interaction (Ti-O-P bonds) formed at the BP-MXene interfaces not only enhances the atomic charge polarization in the BP-MXene heterostructures, leading to efficient interfacial electron transport, but also stabilizes the 3D porous yet dense architecture with much improved mechanical robustness. Consequently, fully packaged SCs using the BP@MXene composite films with a practical-level of mass loading (∼15 mg cm-2) deliver a high stack volumetric energy density of 72.6 Wh L-1, approaching those of lead-acid batteries (50-90 Wh L-1), together with a long-term stability (90.58% capacitance retention after 50000 cycles). The achievement of such high energy density bridges the gap between traditional batteries and SCs and represents a timely breakthrough in designing compact electrodes toward commercial-level capacitive energy storage.

Ceramic-Polymer Composite Membranes for Water and Wastewater Treatment: Bridging the Big Gap between Ceramics and Polymers.

Clean water supply is an essential element for the entire sustainable human society, and the economic and technology development. Membrane filtration for water and wastewater treatments is the premier choice due to its high energy efficiency and effectiveness, where the separation is performed by passing water molecules through purposely tuned pores of membranes selectively without phase change and additional chemicals. Ceramics and polymers are two main candidate materials for membranes, where the majority has been made of polymeric materials, due to the low cost, easy processing, and tunability in pore configurations. In contrast, ceramic membranes have much better performance, extra-long service life, mechanical robustness, and high thermal and chemical stabilities, and they have also been applied in gas, petrochemical, food-beverage, and pharmaceutical industries, where most of polymeric membranes cannot perform properly. However, one of the main drawbacks of ceramic membranes is the high manufacturing cost, which is about three to five times higher than that of common polymeric types. To fill the large gap between the competing ceramic and polymeric membranes, one apparent solution is to develop a ceramic-polymer composite type. Indeed, the properly engineered ceramic-polymer composite membranes are able to integrate the advantages of both ceramic and polymeric materials together, providing improvement in membrane performance for efficient separation, raised life span and additional functionalities. In this overview, we first thoroughly examine three types of ceramic-polymer composite membranes, (i) ceramics in polymer membranes (nanocomposite membranes), (ii) thin film nanocomposite (TFN) membranes, and (iii) ceramic-supported polymer membranes. In the past decade, great progress has been made in improving the compatibility between ceramics and polymers, while the synergy between them has been among the main pursuits, especially in the development of the high performing nanocomposite membranes for water and wastewater treatment at lowered manufacturing cost. By looking into strategies to improve the compatibility among ceramic and polymeric components, we will conclude with briefing on the perspectives and challenges for the future development of the composite membranes.

Overcoming the Trade-off between Water Permeation and Mechanical Strength of Ceramic Membrane Supports by Interfacial Engineering.

Porous ceramic membrane supports with high mechanical strength and permeation are required for highly permeable ceramic membranes. The water permeation of a ceramic membrane support is largely dependent on its level of open porosity, which can be however generally detrimental to the mechanical strength. In this work, low-cost kaolin nanoflakes were rationally composited with coarse alumina particles, and multichannel flat-sheet ceramic supports were successfully fabricated by extrusion and subsequent partial sintering. The macroscopic properties, microstructure characteristics, permeability, and mechanical strength of the ceramic membrane supports were systematically established and comprehensively studied. The incorporation of kaolin nanoflakes effectively reduced the sintering temperature to about 1200 °C. An interesting evolution of the pore structure was evidenced with the increase in sintering temperature. Interestingly, the porous ceramic supports prepared at 1400 °C with a nominal pore size of 1.47 µm showed the highest water permeability of 9911.9 ± 357.5 LMHB, and at the same time the flexural strength reached 109.6 ± 4.6 MPa. The much improved permeability was attributed to the unique multilevel pore structures, and the enhanced flexural strength mainly originated from the strongly interfacial bonding, as evidenced by the trans-granular fracture behavior. Also, the ceramic membrane supports exhibited excellent chemical resistance and good removal efficiency for oily wastewater. This work highlights the significant role of interfacial engineering in simultaneously improving the water permeation and mechanical strength, thereby overcoming their trade-off in porous ceramic membrane supports.

A self-cleaning zwitterionic nanofibrous membrane for highly efficient oil-in-water separation.

The oil and bacteria adhesion during membrane separation process brings great challenges to the operation costs and membrane service life. Meantime, the strong chemical corrosion in sewage seriously limits the durability of membrane as well. Herein, a facile strategy is developed for fabricating highly stable and efficient zwitterionic nanofibrous membrane (NFM) with self-cleaning feature via the combination of in-situ cross-linking of poly (sulfobetaine methacrylate) (PSBMA) and electrospun poly (ether sulfone) (PES) nanofibers. Owing to the introduction of zwitterionic functional groups, the PSBMA/PES NFM exhibits superior antifouling ability (over 3 cycles of crude oil fouling/self-cleaning and up to 7 days of bacteria adhesion/repelling tests). Moreover, the membrane also presents remarkable chemical stability in acidic, alkaline and salty environments; and exhibits excellent separation performance for both layered oil/water mixture and oil-in-water emulsion as well. Furthermore, the membrane is capable to remove bacteria during the continuous oil/water mixture separation. Overall, the proposed strategy provides a new perspective into developing long-term antifouling membrane materials for complicated oily wastewater remediation in various corrosive environments.

Dendrite-Free Potassium Metal Anodes in a Carbonate Electrolyte.

Potassium (K) metal anodes suffer from a challenging problem of dendrite growth. Here, it is demonstrated that a tailored current collector will stabilize the metal plating-stripping behavior even with a conventional KPF6 -carbonate electrolyte. A 3D copper current collector is functionalized with partially reduced graphene oxide to create a potassiophilic surface, the electrode being denoted as rGO@3D-Cu. Potassiophilic versus potassiophobic experiments demonstrate that molten K fully wets rGO@3D-Cu after 6 s, but does not wet unfunctionalized 3D-Cu. Electrochemically, a unique synergy is achieved that is driven by interfacial tension and geometry: the adherent rGO underlayer promotes 2D layer-by-layer (Frank-van der Merwe) metal film growth at early stages of plating, while the tortuous 3D-Cu electrode reduces the current density and geometrically frustrates dendrites. The rGO@3D-Cu symmetric cells and half-cells achieve state-of-the-art plating and stripping performance. The symmetric rGO@3D-Cu cells exhibit stable cycling at 0.1-2 mA cm-2 , while baseline Cu prematurely fails when the current reaches 0.5 mA cm-2 . The half-cells cells of rGO@3D-Cu (no K reservoir) are stable at 0.5 mA cm-2 for 10 000 min (100 cycles), and at 1 mA cm-2 for 5000 min. The baseline 3D-Cu, planar rGO@Cu, and planar Cu foil fails after 5110, 3012, and 1410 min, respectively.

CuCo2S4 Nanosheets@N-Doped Carbon Nanofibers by Sulfurization at Room Temperature as Bifunctional Electrocatalysts in Flexible Quasi-Solid-State Zn-Air Batteries.

The performance of quasi-solid-state flexible zinc-air batteries (ZABs) is critically dependent on the advancement of air electrodes with outstanding bifunctional electrocatalysis for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), together with the desired mechanical flexibility and robustness. The currently available synthesis processes for high-efficiency bifunctional bimetallic sulfide electrodes typically require high-temperature hydrothermal or chemical vapor deposition, which is undesirable in terms of the complexity in experimental procedure and the damage of flexibility in the resultant electrode. Herein, a scalable fabrication process is reported by combining electrospinning with in situ sulfurization at room temperature to successfully obtain CuCo2S4 nanosheets@N-doped carbon nanofiber (CuCo2S4 NSs@N-CNFs) films, which show remarkable bifunctional catalytic performance (Ej = 10 (OER) - E 1/2 (ORR) = 0.751 V) with excellent mechanical flexibility. Furthermore, the CuCo2S4 NSs@N-CNFs cathode delivers a high open-circuit potential of 1.46 V, an outstanding specific capacity of 896 mA h g-1, when assembled into a quasi-solid-state flexible ZAB together with Zn NSs@carbon nanotubes (CNTs) film (electrodeposited Zn nanosheets on CNTs film) as the anode. The ZAB also shows a good flexibility and capacity stability with 93.62% capacity retention (bending 1000 cycles from 0° to 180°), making it an excellent power source for portable and wearable electronic devices.

Nucleoporin 62-Like Protein is Required for the Development of Pharyngeal Arches through Regulation of Wnt/ß-Catenin Signaling and Apoptotic Homeostasis in Zebrafish.

We have previously observed the predominant expression of nucleoporin 62-like (Nup62l) mRNA in the pharyngeal region of zebrafish, which raises the question whether Nup62l has important implications in governing the morphogenesis of pharyngeal arches (PA) in zebrafish. Herein, we explored the functions of Nup62l in PA development. The disruption of Nup62l with a CRISPR/Cas9-dependent gene knockout approach led to defective PA, which was characterized by a thinned and shortened pharyngeal region and a significant loss of pharyngeal cartilages. During pharyngeal cartilage formation, prechondrogenic condensation and chondrogenic differentiation were disrupted in homozygous nup62l-mutants, while the specification and migration of cranial neural crest cells (CNCCs) were unaffected. Mechanistically, the impaired PA region of nup62l-mutants underwent extensive apoptosis, which was mainly dependent on activation of p53-dependent apoptotic pathway. Moreover, aberrant activation of a series of apoptotic pathways in nup62l-mutants is closely associated with the inactivation of Wnt/ß-catenin signaling. Thus, these findings suggest that the regulation of Wnt/ß-catenin activity by Nup62l is crucial for PA formation in zebrafish.

Hierarchical Micro-Nano Sheet Arrays of Nickel-Cobalt Double Hydroxides for High-Rate Ni-Zn Batteries.

The rational design of nickel-based cathodes with highly ordered micro-nano hierarchical architectures by a facile process is fantastic but challenging to achieve for high-capacity and high-rate Ni-Zn batteries. Herein, a one-step etching-deposition-growth process is demonstrated to prepare hierarchical micro-nano sheet arrays for Ni-Zn batteries with outstanding performance and high rate. The fabrication process is conducted at room temperature without any need of heating and stirring, and the as-grown nickel-cobalt double hydroxide (NiCo-DH) supported on conductive nickel substrate is endowed with a unique 3D hierarchical architecture of micro-nano sheet arrays, which empower the effective exposure of active materials, easy electrolyte access, fast ion diffusion, and rapid electron transfer. Benefiting from these merits in combination, the NiCo-DH electrode delivers a high specific capacity of 303.6 mAh g-1 and outstanding rate performance (80% retention after 20-fold current increase), which outperforms the electrodes made of single Ni(OH)2 and Co(OH)2, and other similar materials. The NiCo-DH electrode, when employed as the cathode for a Ni-Zn battery, demonstrates a high specific capacity of 329 mAh g-1. Moreover, the NiCo-DH//Zn battery also exhibits high electrochemical energy conversion efficiency, excellent rate capability (62% retention after 30-fold current increase), ultrafast charge characteristics, and strong tolerance to the high-speed conversion reaction.

AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate.

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.

Heterogeneous ZIF-L membranes with improved hydrophilicity and anti-bacterial adhesion for potential application in water treatment.

Although different metal-organic framework (MOF) membranes have been widely studied for gas separation, their application for water treatment is still in its infancy. MOF membranes with improved hydrophilicity and stability are particularly essential for water/wastewater treatment. Herein, we have successfully developed heterogeneous membranes (Zn/Co-ZIF-L) composed of vertically standing leaf-like crystals of Zn-ZIF-L grown in situ onto porous ceramic supports, followed by the subsequent heterogeneous growth of Co-ZIF-L. The heterogeneous membranes show improved hydrophilicity (WCA = 13.6 ± 1.6°) and enhanced anti-bacterial adhesion. Significantly, they simultaneously deliver a relative high water flux and much improved anti-bacterial adhesion when compared with the homogeneous membranes (Co-ZIF-L and Zn-ZIF-L). The improvements are attributed to the intrinsic hydrophilic nature of Co-ZIF-L, their epitaxial growth onto Zn-ZIF-L as well as the increased surface roughness. The success of constructing a heterogeneous MOF structure shows an effective strategy to achieve the hydrophilic MOF membranes with considerably enhanced stability for water treatment.

A minimally invasive approach to induce myocardial infarction in mice without thoracotomy.

Acute myocardial infarction (MI) is a leading cause of morbidity and mortality in the world. Traditional method to induce MI by left coronary artery (LCA) ligation is typically performed by an invasive approach that requires ventilation and thoracotomy, causing serious injuries in animals undergoing this surgery. We attempted to develop a minimally invasive method (MIM) to induce MI in mice. Under the guide of ultrasound, LCA ligation was performed in mice without ventilation and chest-opening. Compared to sham mice, MIM induced MI in mice as determined by triphenyltetrazolium chloride staining and Masson staining. Mice with MIM surgery revealed the reductions of LVEF, LVFS, E/A and ascending aorta (AAO) blood flow, and the elevations of S-T segment and serum cTn-I levels at 24 post-operative hours. The effects of MI induced by MIM were comparable to the effects of MI produced by traditional method in mice. Importantly, MIM increased the survival rates and caused less inflammation after the surgery of LCA ligation, compared to the surgery of traditional method. Further, MIM induced angiogenesis and apoptosis in ischaemic hearts from mice at postoperative 28 days as similarly as traditional method did. Finally, the MIM model was able to develop into the myocardial ischaemia/reperfusion model by using a balloon catheter with minor modifications. The MI model is able to be efficiently induced by a minimally invasive approach in mice without ventilation and chest-opening. This new model is potentially to be used in studying ischaemia-related heart diseases.

TBX20 Regulates Angiogenesis Through the Prokineticin 2-Prokineticin Receptor 1 Pathway.

BACKGROUND: Angiogenesis is integral for embryogenesis, and targeting angiogenesis improves the outcome of many pathological conditions in patients. TBX20 is a crucial transcription factor for embryonic development, and its deficiency is associated with congenital heart disease. However, the role of TBX20 in angiogenesis has not been described. METHODS: Loss- and gain-of-function approaches were used to explore the role of TBX20 in angiogenesis both in vitro and in vivo. Angiogenesis gene array was used to identify key downstream targets of TBX20. RESULTS: Unbiased gene array survey showed that TBX20 knockdown profoundly reduced angiogenesis-associated PROK2 (prokineticin 2) gene expression. Indeed, loss of TBX20 hindered endothelial cell migration and in vitro angiogenesis. In a murine angiogenesis model using subcutaneously implanted Matrigel plugs, we observed that TBX20 deficiency markedly reduced PROK2 expression and restricted intraplug angiogenesis. Furthermore, recombinant PROK2 administration enhanced angiogenesis and blood flow recovery in murine hind-limb ischemia. In zebrafish, transient knockdown of tbx20 by morpholino antisense oligos or genetic disruption of tbx20 by CRISPR/Cas9 impaired angiogenesis. Furthermore, loss of prok2 or its cognate receptor prokr1a also limited angiogenesis. In contrast, overexpression of prok2 or prokr1a rescued the impaired angiogenesis in tbx20-deficient animals. CONCLUSIONS: Our study identifies TBX20 as a novel transcription factor regulating angiogenesis through the PROK2-PROKR1 (prokineticin receptor 1) pathway in both development and disease and reveals a novel mode of angiogenic regulation whereby the TBX20-PROK2-PROKR1 signaling cascade may act as a "biological capacitor" to relay and sustain the proangiogenic effect of vascular endothelial growth factor. This pathway may be a therapeutic target in the treatment of diseases with dysregulated angiogenesis.

Lmo2 (LIM-Domain-Only 2) Modulates Sphk1 (Sphingosine Kinase) and Promotes Endothelial Cell Migration.

OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) y1 zebrafish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1. EC proliferation in vivo was assessed by BrdU (bromodeoxyuridine) immunostaining and fluorescence-activated cell sorter analysis of dissociated Tg(fli1:EGFP) y1 embryos. Cell migration was assessed by scratch assay in human umbilical vein EC and mouse aortic rings. Lmo2 interactions with Sphk1 promoter were assessed by ChIP-PCR (chromatin immunoprecipitation-polymerase chain reaction). Lmo2 or Sphk1 KD reduced number and length of intersegmental vessels. There was no reduction in the numbers of GFP+ (green fluorescent protein) ECs after Lmo2 KD. However, reduced numbers of BrdU+GFP+ nuclei were observed along the dysmorphic intersegmental vessels, accumulating instead at the sprouting origin of the intersegmental vessels. This anomaly was likely because of impaired EC migration, which was confirmed in migration assays using Lmo2 KD human umbilical vein ECs and mouse aortic rings. Both in vivo and in vitro, Lmo2 KD reduced Sphk1 gene expression, associated with less Lmo2 binding to the Sphk1 promoter as assessed by ChIP-PCR. Sphk1 mRNA rescued the Lmo2 KD phenotype. CONCLUSIONS: Our data showed that Lmo2 is necessary for Sphk1 gene expression in ECs. Lmo2 KD reduced Lmo2-Sphk1 gene interaction, impaired intersegmental vessels formation, and reduced cell migration. We identified for the first time Sphk1 as downstream effector of Lmo2.

AIBP Limits Angiogenesis Through γ-Secretase-Mediated Upregulation of Notch Signaling.

RATIONALE: Angiogenesis improves perfusion to the ischemic tissue after acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that AIBP (apolipoprotein A-I [apoA-I]-binding protein)-regulated cholesterol efflux in endothelial cells controls zebra fish embryonic angiogenesis. OBJECTIVE: This study is to determine whether loss of AIBP affects angiogenesis in mice during development and under pathological conditions and to explore the underlying molecular mechanism. METHODS AND RESULTS: In this article, we report the generation of AIBP knockout (Apoa1bp-/-) mice, which are characterized of accelerated postnatal retinal angiogenesis. Mechanistically, AIBP triggered relocalization of γ-secretase from lipid rafts to nonlipid rafts where it cleaved Notch. Consistently, AIBP treatment enhanced DLL4 (delta-like ligand 4)-stimulated Notch activation in human retinal endothelial cells. Increasing high-density lipoprotein levels in Apoa1bp-/- mice by crossing them with apoA-I transgenic mice rescued Notch activation and corrected dysregulated retinal angiogenesis. Notably, the retinal vessels in Apoa1bp-/- mice manifested normal pericyte coverage and vascular integrity. Similarly, in the subcutaneous Matrigel plug assay, which mimics ischemic/inflammatory neovascularization, angiogenesis was dramatically upregulated in Apoa1bp-/- mice and associated with a profound inhibition of Notch activation and reduced expression of downstream targets. Furthermore, loss of AIBP increased vascular density and facilitated the recovery of blood vessel perfusion function in a murine hindlimb ischemia model. In addition, AIBP expression was significantly increased in human patients with ischemic cardiomyopathy. CONCLUSIONS: Our data reveal a novel mechanistic connection between AIBP-mediated cholesterol metabolism and Notch signaling, implicating AIBP as a possible druggable target to modulate angiogenesis under pathological conditions.