Heparan Sulfate–Editing Extracellular Sulfatases Enhance VEGF Bioavailability for Ischemic Heart Repair

OBJECTIVE: We identified the sulfatase SULF2 in an in silico secretome analysis in bone marrow cells from patients with acute myocardial infarction and detected increased sulfatase activity in myocardial autopsy samples. SULF2 (Sulf2 in mice) and its isoform SULF1 (Sulf1) act as endosulfatases removing 6-O-sulfate groups from heparan sulfate (HS) in the extracellular space, thus eliminating docking sites for HS-binding proteins. We hypothesized that the Sulfs have a role in tissue repair after myocardial infarction.

[1]  A. Chambery,et al.  TRF2 positively regulates SULF2 expression increasing VEGF-A release and activity in tumor microenvironment , 2019, Nucleic acids research.

[2]  J. Gogos,et al.  EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow–Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction , 2017, Circulation.

[3]  Bernd Hertenstein,et al.  Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial , 2017, European heart journal.

[4]  C. Held,et al.  Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995–2014 , 2017, European heart journal.

[5]  S. Thorgeirsson,et al.  Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma. , 2017, Cancer research.

[6]  S. Prabhu,et al.  The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. , 2016, Circulation research.

[7]  Edwin Wu,et al.  Inflammation as a Driver of Adverse Left Ventricular Remodeling After Acute Myocardial Infarction. , 2016, Journal of the American College of Cardiology.

[8]  C. Granger,et al.  Relationship Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 10 Randomized Trials. , 2016, Journal of the American College of Cardiology.

[9]  C. Hodgkinson,et al.  Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology. , 2016, Circulation research.

[10]  T. Dierks,et al.  Sulf1 and Sulf2 Differentially Modulate Heparan Sulfate Proteoglycan Sulfation during Postnatal Cerebellum Development: Evidence for Neuroprotective and Neurite Outgrowth Promoting Functions , 2015, PloS one.

[11]  C. Moser,et al.  Activation of the transforming growth factor‐β/SMAD transcriptional pathway underlies a novel tumor‐promoting role of sulfatase 1 in hepatocellular carcinoma , 2015, Hepatology.

[12]  A. Ganser,et al.  Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction , 2015, Nature Medicine.

[13]  Doris A Taylor,et al.  Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial. , 2015, Circulation research.

[14]  J. Esko,et al.  Demystifying heparan sulfate-protein interactions. , 2014, Annual review of biochemistry.

[15]  A. Zeiher,et al.  Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival. , 2014, European heart journal.

[16]  S. Heymans,et al.  Myocardial Extracellular Matrix: An Ever-Changing and Diverse Entity , 2014, Circulation research.

[17]  J. Piek,et al.  Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. , 2014, European heart journal.

[18]  Aleksander S Popel,et al.  Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning. , 2014, Cytokine & growth factor reviews.

[19]  A. Harris,et al.  The heparan sulfate editing enzyme Sulf1 plays a novel role in zebrafish VegfA mediated arterial venous identity , 2013, Angiogenesis.

[20]  Jun Jiang,et al.  Quantitative Phosphoproteomics Analysis Reveals Broad Regulatory Role of Heparan Sulfate on Endothelial Signaling* , 2013, Molecular & Cellular Proteomics.

[21]  G. Lip,et al.  CXCR4 positive and angiogenic monocytes in myocardial infarction , 2012, Thrombosis and Haemostasis.

[22]  G. Jayson,et al.  Endothelial Heparan Sulfate 6-O-Sulfation Levels Regulate Angiogenic Responses of Endothelial Cells to Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor* , 2012, The Journal of Biological Chemistry.

[23]  S. Stahl,et al.  Targeted disruption of heparan sulfate interaction with hepatocyte and vascular endothelial growth factors blocks normal and oncogenic signaling. , 2012, Cancer cell.

[24]  D. Rowitch,et al.  Heparan sulfate sulfatase SULF2 regulates PDGFRα signaling and growth in human and mouse malignant glioma. , 2012, The Journal of clinical investigation.

[25]  T. Dierks,et al.  Roles of Heparan Sulfate Sulfation in Dentinogenesis* , 2012, The Journal of Biological Chemistry.

[26]  M. Masu,et al.  Organ-specific Sulfation Patterns of Heparan Sulfate Generated by Extracellular Sulfatases Sulf1 and Sulf2 in Mice* , 2012, The Journal of Biological Chemistry.

[27]  Lu Cao,et al.  hSulf-1 Gene Exhibits Anticancer Efficacy through Negatively Regulating VEGFR-2 Signaling in Human Cancers , 2011, PloS one.

[28]  J. Esko,et al.  Heparan sulfate proteoglycans. , 2011, Cold Spring Harbor perspectives in biology.

[29]  Yuquan Wei,et al.  SKLB1002, a Novel Potent Inhibitor of VEGF Receptor 2 Signaling, Inhibits Angiogenesis and Tumor Growth In Vivo , 2011, Clinical Cancer Research.

[30]  Chi-Huey Wong,et al.  Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways , 2010, Proceedings of the National Academy of Sciences.

[31]  A. Zeiher,et al.  CXCR4 Expression Determines Functional Activity of Bone Marrow–Derived Mononuclear Cells for Therapeutic Neovascularization in Acute Ischemia , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[32]  A. Ganser,et al.  Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction. , 2008, European heart journal.

[33]  T. Dierks,et al.  Sulf Loss Influences N-, 2-O-, and 6-O-Sulfation of Multiple Heparan Sulfate Proteoglycans and Modulates Fibroblast Growth Factor Signaling* , 2008, Journal of Biological Chemistry.

[34]  C. Glass,et al.  Surfen, a small molecule antagonist of heparan sulfate , 2008, Proceedings of the National Academy of Sciences.

[35]  S. Rafii,et al.  The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. , 2007, Trends in immunology.

[36]  M. Tessier-Lavigne,et al.  Secreted Sulfatases Sulf1 and Sulf2 Have Overlapping yet Essential Roles in Mouse Neonatal Survival , 2007, PloS one.

[37]  T. Dierks,et al.  Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. , 2006, The Biochemical journal.

[38]  J. Chien,et al.  HSulf-1 inhibits angiogenesis and tumorigenesis in vivo. , 2006, Cancer research.

[39]  L. Claesson‐Welsh,et al.  VEGF receptor signalling ? in control of vascular function , 2006, Nature Reviews Molecular Cell Biology.

[40]  Christopher J. Robinson,et al.  VEGF165-binding Sites within Heparan Sulfate Encompass Two Highly Sulfated Domains and Can Be Liberated by K5 Lyase* , 2006, Journal of Biological Chemistry.

[41]  J. Gallagher,et al.  HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1 , 2006, BMC Biochemistry.

[42]  K. Kimata,et al.  Heparin Regulates Vascular Endothelial Growth Factor165-dependent Mitogenic Activity, Tube Formation, and Its Receptor Phosphorylation of Human Endothelial Cells , 2005, Journal of Biological Chemistry.

[43]  A. Ganser,et al.  Monitoring of Bone Marrow Cell Homing Into the Infarcted Human Myocardium , 2005, Circulation.

[44]  L. Claesson‐Welsh,et al.  The Adaptor Protein Shb Binds to Tyrosine 1175 in Vascular Endothelial Growth Factor (VEGF) Receptor-2 and Regulates VEGF-dependent Cellular Migration* , 2004, Journal of Biological Chemistry.

[45]  Z. Werb,et al.  Cloning and Characterization of Two Extracellular Heparin-degrading Endosulfatases in Mice and Humans* , 2002, The Journal of Biological Chemistry.

[46]  R. Brekken,et al.  Vascular endothelial growth factor as a marker of tumor endothelium. , 1998, Cancer research.

[47]  T. Ruzicka,et al.  [Granulomatous allergic reaction of the delayed type to surfen]. , 1981, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[48]  S. Fisher,et al.  Stem cell treatment for acute myocardial infarction. , 2012, The Cochrane database of systematic reviews.