A5100743600- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- Peptidase Inhibition and Analysis
- Cardiac Valve Diseases and Treatments
- Aortic aneurysm repair treatments
- Calcium signaling and nucleotide metabolism
- Axon Guidance and Neuronal Signaling
- Cancer-related molecular mechanisms research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Aortic Disease and Treatment Approaches
- Lymphatic System and Diseases
- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- RNA modifications and cancer
- Transplantation: Methods and Outcomes
- Geological and Geochemical Analysis
- Ion channel regulation and function
- Cancer, Hypoxia, and Metabolism
- Coronary Interventions and Diagnostics
- Blood Coagulation and Thrombosis Mechanisms
- Ubiquitin and proteasome pathways
- Kruppel-like factors research
- Connective tissue disorders research
Yale University
2015-2025
VA Connecticut Healthcare System
2013-2025
The First Affiliated Hospital, Sun Yat-sen University
2023-2025
Sun Yat-sen University
2023-2025
First Affiliated Hospital of Fujian Medical University
2022-2024
Fujian Medical University
2022-2024
Hangzhou First People's Hospital
2024
Zhejiang Chinese Medical University
2024
Westlake University
2024
First Affiliated Hospital of Guangzhou Medical University
2023
Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level capillary endothelium lining metabolically active tissues. How large blood vessels, site atherosclerotic vascular disease, regulate flux fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) not known. In this study, we showed that deletion enzyme, adipose lipase (ATGL) in...
Neuropilin 1 (NRP1) plays an important but ill-defined role in VEGF-A signaling and vascular morphogenesis. We show that mice with a knockin mutation ablates the NRP1 cytoplasmic tail (Nrp1cyto) have normal angiogenesis impaired developmental adult arteriogenesis. The arteriogenic defect was traced to absence of PDZ-dependent interaction between VEGF receptor 2 (VEGFR2) complex synectin, which delayed trafficking endocytosed VEGFR2 from Rab5+ EAA1+ endosomes. This led increased PTPN1...
Abstract Tetrahydroisoquinoline alkaloids with a C1 stereogenic center are common unit in many natural and non‐natural compounds of biological importance. Herein we describe novel Cu I ‐catalyzed highly chemo‐ enantioselective synthesis chiral tetrahydroisoquinoline‐alkaloid derivatives from readily available unsubstituted tetrahydroisoquinolines, aldehydes, terminal alkynes the presence ligand ( R , )‐N‐pinap. This synthetic operation installs two substituents 1‐ 2‐positions.
Regulation of vascular endothelial growth factor receptor-2 (VEGFR2) signaling is a control point that determines the extent tree formation. Recent studies demonstrated an important role played by VEGFR2 trafficking in its activity and suggested involvement phosphotyrosine phosphatase 1b (PTP1b) this process. This study was designed to define PTP1b regulation angiogenesis arteriogenesis.We generated mice carrying endothelial-specific deletion examined effect knockout on VEGF signaling,...
Background— Noninvasive imaging strategies play a critical role in assessment of the efficacy angiogenesis therapies. The α v β 3 integrin is activated angiogenic vessels and represents potential target for noninvasive angiogenesis. Methods Results— We evaluated 99m Tc-labeled peptide (NC100692) targeted at an established murine model induced by hindlimb ischemia. Control mice (n=9) or with surgical right femoral artery occlusion (n=29) were injected NC100692 (1.5±0.2 mCi IV) different times...
Background— Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is novel indium 111 In–labeled tracer with specificity for activated MMPs. We hypothesized that can detect injury-induced remodeling vivo. Methods and Results— Left common carotid artery injury was induced guidewire apolipoprotein E −/− mice. Sham surgery performed on the contralateral artery, which served as control imaging experiments. Carotid wire led to significant hyperplasia expansive...
Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of flow control, how arterial innervation develops remains largely unknown. Here, we identified axon guidance cue netrin-1 as an essential factor required for development in mice. Netrin-1 was produced by smooth muscle cells (SMCs) at onset innervation, interaction with its receptor, deleted colorectal cancer (DCC),...
Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target number of diseases, including wet macular degeneration wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow extension. The adaptor proteins Nck1 2 are known regulators cytoskeletal dynamics polarity, but their function poorly understood. Here, we show that Nck adaptors required for endothelial cell migration downstream angiogenic...
Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD) by unknown mechanisms. Here, we show that reduced activity LRP6R611C mice promotes loss of vascular smooth muscle cell (VSMC) differentiation, leading aortic medial hyperplasia. Carotid injury augmented these effects and led partial total obstruction. on high-fat diet displayed dramatic obstructive CAD exhibited an accelerated atherosclerotic burden LDLR knockout background. Mechanistically, impaired...
Abstract The proteoglycan Syndecan-2 (Sdc2) has been implicated in regulation of cytoskeleton organization, integrin signaling and developmental angiogenesis zebrafish. Here we report that mice with global inducible endothelial-specific deletion Sdc2 display marked angiogenic arteriogenic defects impaired VEGFA 165 signaling. No such abnormalities are observed the closely related Syndecan-4 (Sdc4) gene. These differences due to a significantly higher 6-O sulfation level versus Sdc4 heparan...
Significance Angiogenesis, or new blood vessel formation, is critical not only for normal processes such as embryonic development but also progression of diseases tumor growth, metastasis, and chronic inflammatory disease. This work elucidated a molecular mechanism that important in postnatal angiogenesis growth ischemia–reperfusion injury the hind limb. Specifically, we identified posttranscriptional gene regulatory controls activity potent suppressor expression, named eIF4e transporter...
The alpha(v)beta3 integrin plays a critical role in cell proliferation and migration. We hypothesized that vascular proliferation, hallmark of injury-induced remodeling, can be tracked by targeting expression vivo.RP748, novel 111In-labeled alpha(v)beta3-specific radiotracer, was evaluated for its cell-binding characteristics ability to track vivo. Three groups experiments were performed. In cultured endothelial cells (ECs), TA145, cy3-labeled homologue RP748, localized at focal contacts....
The cellular response to stress involves the recruitment and coordination of molecular signaling pathways that prevent cell death. D-dopachrome tautomerase (DDT) is an enzyme lacks physiologic substrates in mammalian cells, but shares partial sequence structural homology with macrophage migration inhibitory factor (MIF). Here, we observed DDT highly expressed murine cardiomyocytes secreted by heart after ischemic stress. Antibody-dependent neutralization exacerbated both ischemia-induced...
Arteriogenesis is the process of formation arterial conduits. Its promotion an attractive therapeutic strategy in occlusive atherosclerotic diseases. Despite functional and clinical importance arteriogenesis, biology poorly understood. Synectin, a gene previously implicated regulation vascular endothelial cell growth factor signaling, offers unique opportunity to determine relative contributions various types arteriogenesis.We investigated cell-autonomous effects synectin knockout...
Aberrant blood vessel formation contributes to a wide variety of pathologies, and factors that regulate angiogenesis are attractive therapeutic targets. Endothelial smooth muscle cell-derived neuropilin-like protein (ESDN) is neuropilin-related transmembrane expressed in ECs; however, its potential effect on VEGF responses remains undefined. Here, we generated global EC-specific Esdn knockout mice demonstrated ESDN promotes VEGF-induced human murine EC proliferation migration. Deletion the...
Matrix metalloproteinases (MMPs) play a key role in the development of atherosclerosis and its complications. In vivo detection quantification MMP activation can help track propensity to complications response therapy. We sought establish an imaging approach for monitoring atherosclerotic mouse aorta use it assess dietary modification. <b>Method:</b> Apolipoprotein-deficient mice were fed normal chow or high-fat diet (HFD) up 3 mo HFD 2 mo, followed by 1 on chow. Then they underwent...
The aorta is the largest artery in body, yet processes underlying aortic pathology are poorly understood. arterial media consists of circumferential layers elastic lamellae and smooth muscle cells (SMCs), many diseases characterized by defective excess SMCs; however, a mechanism linking these pathological features lacking. In this study, we use lineage genetic analysis, pharmacological inhibition, explant cultures, induced pluripotent stem (iPSCs) to investigate supravalvular stenosis (SVAS)...
Abstract Vascular permeability and neovascularization are implicated in many diseases including retinopathies diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown −/− mice develop hyperpermeability, but how signals remained unclear. Here we show deletion enhances revascularization oxygen-induced retinopathy (OIR) accelerates cutaneous To determine signalling pathways, generated transgenic expressing a truncated lacking...
Abstract Background Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal in China. This study was to develop a staging model predict outcomes patients with ESCC. Methods Using Cox regression analysis, principal component analysis (PCA), partitioning clustering, Kaplan–Meier receiver operating characteristic (ROC) curve and classification tree (CART) we mined Gene Expression Omnibus database determine expression profiles genes 179 ESCC from GSE63624 GSE63622...