Targeting VCAM-1: a therapeutic opportunity for vascular damage

INTRODUCTION The vascular cell adhesion molecule (VCAM-1) is a transmembrane sialoglycoprotein detected in activated endothelial and vascular smooth muscle cells involved in the adhesion and transmigration of inflammatory cells into damaged tissue. Widely used as a pro-inflammatory marker, its potential role as a targeting molecule has not been thoroughly explored. Areas covered: We discuss the current evidence supporting the potential targeting of VCAM-1 in atherosclerosis, diabetes, hypertension and ischemia/reperfusion injury. EXPERT OPINION There is emerging evidence that VCAM-1 is more than a biomarker and may be a promising therapeutic target for vascular diseases. While there are neutralizing antibodies that allow preclinical research, the development of pharmacological tools to activate or inhibit this protein are required to thoroughly assess its therapeutic potential.

[1]  A. Huang,et al.  Ectopic Tumor VCAM-1 Expression in Cancer Metastasis and Therapy Resistance , 2022, Cells.

[2]  N. Yano,et al.  Critical Functions of Histone Deacetylases (HDACs) in Modulating Inflammation Associated with Cardiovascular Diseases , 2022, Pathophysiology : the official journal of the International Society for Pathophysiology.

[3]  P. Little,et al.  Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis , 2022, Frontiers in Cardiovascular Medicine.

[4]  Jihong Han,et al.  MEK1/2 inhibitor inhibits neointima formation by activating miR-126-3p/ C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) axis , 2022, Bioengineered.

[5]  P. Pagliaro,et al.  Challenges facing the clinical translation of cardioprotection: 35 years after the discovery of ischemic preconditioning. , 2022, Vascular pharmacology.

[6]  Li-Long Pan,et al.  PRMT5 critically mediates TMAO-induced inflammatory response in vascular smooth muscle cells , 2022, Cell Death & Disease.

[7]  Chiang-Wen Lee,et al.  Carbon monoxide releasing molecule-2 attenuates angiotensin II-induced IL-6/Jak2/Stat3-associated inflammation by inhibiting NADPH oxidase- and mitochondria-derived ROS in human aortic smooth muscle cells. , 2022, Biochemical pharmacology.

[8]  Y. Liu,et al.  Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice , 2022, Frontiers in Pharmacology.

[9]  I. Ismawati,et al.  Effect of Proteasome Inhibitor on Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) Expressions in Rat Model of Atherosclerosis. , 2022, Reports of biochemistry & molecular biology.

[10]  Shaohua Wang,et al.  Endothelial cell–derived exosomal circHIPK3 promotes the proliferation of vascular smooth muscle cells induced by high glucose via the miR-106a-5p/Foxo1/Vcam1 pathway , 2021, Aging.

[11]  K. Moore,et al.  Reverse cardio-oncology: Exploring the effects of cardiovascular disease on cancer pathogenesis. , 2021, Journal of molecular and cellular cardiology.

[12]  Weerapon Sangartit,et al.  Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats. , 2021, Life sciences.

[13]  J. Hou,et al.  Metformin inhibits cholesterol-induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells , 2021, Molecular medicine reports.

[14]  K. Nicolaides,et al.  First trimester angiogenic and inflammatory factors in women with chronic hypertension and impact of blood pressure control: a case–control study , 2021, BJOG : an international journal of obstetrics and gynaecology.

[15]  G. Drava,et al.  Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting , 2021, Pharmaceutics.

[16]  Shilei Liu,et al.  HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E-selectin/VCAM-1 , 2021, Experimental and therapeutic medicine.

[17]  W. Yeh,et al.  Regulatory effects of IL-1β in the interaction of GBM and tumor-associated monocyte through VCAM-1 and ICAM-1. , 2021, European journal of pharmacology.

[18]  F. Innocenti,et al.  Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance) , 2021, Angiogenesis.

[19]  Fernanda Sanhueza-Olivares,et al.  VCAM-1 as a predictor biomarker in cardiovascular disease. , 2021, Biochimica et biophysica acta. Molecular basis of disease.

[20]  Xing Fan,et al.  HDAC1 and 2 regulate endothelial VCAM-1 expression and atherogenesis by suppressing methylation of the GATA6 promoter , 2021, Theranostics.

[21]  Mei Han,et al.  SM22α Loss Contributes to Apoptosis of Vascular Smooth Muscle Cells via Macrophage-Derived circRasGEF1B , 2021, Oxidative medicine and cellular longevity.

[22]  Shujing Wang,et al.  PRDX2 Protects Against Atherosclerosis by Regulating the Phenotype and Function of the Vascular Smooth Muscle Cell , 2021, Frontiers in Cardiovascular Medicine.

[23]  F. Nettersheim,et al.  Vaccination in Atherosclerosis , 2020, Cells.

[24]  Matthew W. Hagen,et al.  ECHOCARDIOGRAPHIC MOLECULAR IMAGING OF THE EFFECT OF ANTI-CYTOKINE THERAPY FOR ATHEROSCLEROSIS. , 2020, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[25]  R. Foo,et al.  Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation , 2020, Frontiers in Immunology.

[26]  Shao-Lin He,et al.  Neferine suppresses vascular endothelial inflammation by inhibiting the NF-κB signaling pathway. , 2020, Archives of biochemistry and biophysics.

[27]  S. Carlier,et al.  VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques , 2020, Biology.

[28]  H. Moses,et al.  Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism , 2020, Gut.

[29]  Z. Fayad,et al.  Immune Checkpoint Inhibitor Therapy Aggravates T Cell–Driven Plaque Inflammation in Atherosclerosis , 2020, JACC. CardioOncology.

[30]  H. Uzun,et al.  The importance of circulating levels of salusin-α, salusin-β, and heregulin-β1 in atherosclerotic coronary arterial disease. , 2020, Clinical biochemistry.

[31]  B. Segard,et al.  Human cardiac fibroblasts expressing VCAM1 improve heart function in postinfarct heart failure rat models by stimulating lymphangiogenesis , 2020, PloS one.

[32]  E. Lutgens,et al.  Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease , 2020, Journal for ImmunoTherapy of Cancer.

[33]  H. Alzamil Elevated Serum TNF-α Is Related to Obesity in Type 2 Diabetes Mellitus and Is Associated with Glycemic Control and Insulin Resistance , 2020, Journal of obesity.

[34]  E. Bahnson,et al.  Diabetic Vasculopathy: Macro and Microvascular Injury , 2020, Current Pathobiology Reports.

[35]  M. Simionescu,et al.  Pharmacological inhibition of histone deacetylase reduces NADPH oxidase expression, oxidative stress and the progression of atherosclerotic lesions in hypercholesterolemic apolipoprotein E-deficient mice; potential implications for human atherosclerosis , 2019, Redox biology.

[36]  J. Shaw,et al.  Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. , 2019, Diabetes research and clinical practice.

[37]  M. Rafieian-kopaei,et al.  Antioxidants and Atherosclerosis: Mechanistic Aspects , 2019, Biomolecules.

[38]  Y. Devaux,et al.  Immune cells as targets for cardioprotection: new players and novel therapeutic opportunities. , 2019, Cardiovascular research.

[39]  Dinu S. Chandran,et al.  Imbalance between Angiotensin II - Angiotensin (1-7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension. , 2019, Diabetes & metabolic syndrome.

[40]  Prahalathan Pichavaram,et al.  Cholesterol crystals promote endothelial cell and monocyte interactions via H2O2-mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression , 2019, Redox biology.

[41]  Xiao-li Zhang,et al.  Circulating Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1): Relationship with carotid artery elasticity in patients with impaired glucose regulation (IGR). , 2019, Annales d'endocrinologie.

[42]  L. Fernandez-Friera,et al.  Soluble ICAM 1 and VCAM 1 Blood Levels Alert on Subclinical Atherosclerosis in Non Smokers with Asymptomatic Metabolic Syndrome. , 2019, Archives of medical research.

[43]  Laurent S Dumas,et al.  Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis – impact of radiochemistry on pharmacokinetics , 2018, Biological chemistry.

[44]  J. Moriya Critical roles of inflammation in atherosclerosis. , 2019, Journal of cardiology.

[45]  Rui Zhang,et al.  Cardioprotection of Ginkgolide B on Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Regulation of A20-NF-κB Pathway , 2018, Front. Immunol..

[46]  H. Bøtker,et al.  Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection , 2018, Basic Research in Cardiology.

[47]  A. Lopes,et al.  Acute Inflammation and Metabolism , 2018, Inflammation.

[48]  D. Sedding,et al.  Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease , 2018, Front. Immunol..

[49]  M. R. Kim,et al.  Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer , 2018, International journal of molecular sciences.

[50]  M. Cour,et al.  The SAFE pathway for cardioprotection: is this a promising target? , 2018, Basic Research in Cardiology.

[51]  P. Carmeliet,et al.  Endothelial Cell Metabolism. , 2018, Physiological reviews.

[52]  S. David,et al.  Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury. , 2017, The American journal of cardiology.

[53]  Kenneth K. Wu,et al.  Cytokine-induced autophagy promotes long-term VCAM-1 but not ICAM-1 expression by degrading late-phase IκBα , 2017, Scientific Reports.

[54]  K. Stangl,et al.  The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice , 2017, International journal of molecular sciences.

[55]  Junho Chung,et al.  Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis , 2017, Experimental &Molecular Medicine.

[56]  P. Carmeliet,et al.  Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. , 2016, Cancer cell.

[57]  W. Guo,et al.  Correlation of VCAM-1 expression in serum, cord blood, and placental tissue with gestational hypertension associated with fetal growth restriction in women from Xingtai Hebei, China. , 2016, Genetics and molecular research : GMR.

[58]  Matthieu Texier,et al.  Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination , 2016, Nature Reviews Clinical Oncology.

[59]  T. Okano,et al.  Cardiac fibroblast-derived VCAM-1 enhances cardiomyocyte proliferation for fabrication of bioengineered cardiac tissue , 2016, Regenerative therapy.

[60]  A. Nègre-Salvayre,et al.  Oxidative theory of atherosclerosis and antioxidants. , 2016, Biochimie.

[61]  Hai-Jian Sun,et al.  Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway , 2016, Scientific Reports.

[62]  D. Ramji,et al.  Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets , 2015, Cytokine & growth factor reviews.

[63]  M. Cooper,et al.  Direct Endothelial Nitric Oxide Synthase Activation Provides Atheroprotection in Diabetes-Accelerated Atherosclerosis , 2015, Diabetes.

[64]  W. Mu,et al.  Expression of vascular cell adhesion molecule-1 in the aortic tissues of atherosclerotic patients and the associated clinical implications , 2015, Experimental and therapeutic medicine.

[65]  Qing Liu,et al.  Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms , 2015, Evidence-based complementary and alternative medicine : eCAM.

[66]  R. Bai,et al.  Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1 Expression via the MAS Receptor Through Suppression of P38 and NF-κB Pathways in HUVECs , 2015, Cellular Physiology and Biochemistry.

[67]  E. Tuzcu,et al.  Cholesterol crystals associate with coronary plaque vulnerability in vivo. , 2015, Journal of the American College of Cardiology.

[68]  Hong Wang,et al.  Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function , 2014, Journal of Hematology & Oncology.

[69]  M. Hollstein,et al.  VEGF-A isoforms differentially regulate ATF-2–dependent VCAM-1 gene expression and endothelial–leukocyte interactions , 2014, Molecular biology of the cell.

[70]  C. Sobey,et al.  Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension , 2014, BioMed research international.

[71]  C. Napoli,et al.  Epigenetic Reprogramming in Atherosclerosis , 2014, Current Atherosclerosis Reports.

[72]  S. Seidelmann,et al.  Development and pathologies of the arterial wall , 2014, Cellular and Molecular Life Sciences.

[73]  L. Vanhamme,et al.  Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies , 2013, Mediators of inflammation.

[74]  H. Abdala-Valencia,et al.  Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation. , 2013, American journal of physiology. Lung cellular and molecular physiology.

[75]  K. Moon,et al.  Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice. , 2013, Atherosclerosis.

[76]  Hong Chen,et al.  Angiotensin-(1-7) regulates Angiotensin II-induced VCAM-1 expression on vascular endothelial cells. , 2013, Biochemical and biophysical research communications.

[77]  S. Berdnikovs,et al.  Distinct sites within the vascular cell adhesion molecule-1 (VCAM-1) cytoplasmic domain regulate VCAM-1 activation of calcium fluxes versus Rac1 during leukocyte transendothelial migration. , 2012, Biochemistry.

[78]  Junho Chung,et al.  An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion , 2012, The Journal of Immunology.

[79]  J. Ohanian,et al.  Endothelin-1 Stimulates Small Artery VCAM-1 Expression through p38MAPK-Dependent Neutral Sphingomyelinase , 2012, Journal of Vascular Research.

[80]  Timothy L Lash,et al.  25 year trends in first time hospitalisation for acute myocardial infarction, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity: a Danish nationwide cohort study , 2012, BMJ : British Medical Journal.

[81]  H. Abdala-Valencia,et al.  Vascular cell adhesion molecule-1 expression and signaling during disease: regulation by reactive oxygen species and antioxidants. , 2011, Antioxidants & redox signaling.

[82]  S. Davidson Endothelial mitochondria and heart disease. , 2010, Cardiovascular research.

[83]  K. Dharmashankar,et al.  Vascular Endothelial Function and Hypertension: Insights and Directions , 2010, Current hypertension reports.

[84]  T. McGloughlin,et al.  Vascular cell adhesion molecule-1 expression in endothelial cells exposed to physiological coronary wall shear stresses. , 2009, Journal of biomechanical engineering.

[85]  G. Baumann,et al.  Potent anti-inflammatory effects of low-dose proteasome inhibition in the vascular system , 2009, Journal of Molecular Medicine.

[86]  Karl Werdan,et al.  Interaction of vascular smooth muscle cells and monocytes by soluble factors synergistically enhances IL-6 and MCP-1 production. , 2009, American journal of physiology. Heart and circulatory physiology.

[87]  R. Medzhitov Origin and physiological roles of inflammation , 2008, Nature.

[88]  Weibin Shi,et al.  siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration. , 2008, Atherosclerosis.

[89]  Kyu-Won Kim,et al.  Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. , 2008, Biochimica et biophysica acta.

[90]  M. Kitamura,et al.  Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein response. , 2007, Biochemical and biophysical research communications.

[91]  D. Yellon,et al.  Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection , 2007, Heart Failure Reviews.

[92]  T. L. Deem,et al.  VCAM-1 Activation of Endothelial Cell Protein Tyrosine Phosphatase 1B1 , 2007, The Journal of Immunology.

[93]  C. Vrints,et al.  Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. , 2005, International journal of cardiology.

[94]  T. L. Deem,et al.  Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. , 2004, Blood.

[95]  G. Owens,et al.  Molecular regulation of vascular smooth muscle cell differentiation in development and disease. , 2004, Physiological reviews.

[96]  David Handelsman,et al.  Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway. , 2004, Endocrinology.

[97]  T. L. Deem,et al.  Calcium mobilization and Rac1 activation are required for VCAM-1 (vascular cell adhesion molecule-1) stimulation of NADPH oxidase activity. , 2004, The Biochemical journal.

[98]  P. Hordijk,et al.  VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. , 2003, American journal of physiology. Cell physiology.

[99]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[100]  W. Quist,et al.  Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration. , 2001, Journal of vascular surgery.

[101]  Y. W. Lee,et al.  IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells. , 2001, Journal of molecular and cellular cardiology.

[102]  T. L. Deem,et al.  Lymphocyte Migration Through Monolayers of Endothelial Cell Lines Involves VCAM-1 Signaling Via Endothelial Cell NADPH Oxidase1 , 2000, The Journal of Immunology.

[103]  T. Kodama,et al.  A novel cell adhesion inhibitor, K-7174, reduces the endothelial VCAM-1 induction by inflammatory cytokines, acting through the regulation of GATA. , 2000, Biochemical and biophysical research communications.

[104]  T. Yoshikawa,et al.  Inhibitory effects of vitamin E on endothelial-dependent adhesive interactions with leukocytes induced by oxidized low density lipoprotein. , 2000, BioFactors.

[105]  M. Toborek,et al.  Endothelial cell functions.¶Relationship to atherogenesis , 1999, Basic Research in Cardiology.

[106]  J. Mitchell,et al.  Redox imbalance in the critically ill. , 1999, British medical bulletin.

[107]  M. Feldmann,et al.  Role of Tyrosine Kinase Enzymes in TNF‐α and IL‐1 Induced Expression of ICAM‐1 and VCAM‐1 on Human Umbilical Vein Endothelial Cells , 1997, Scandinavian journal of immunology.

[108]  C Chothia,et al.  The molecular structure of cell adhesion molecules. , 1997, Annual review of biochemistry.

[109]  J. Berliner,et al.  Angiotensin II increases monocyte binding to endothelial cells. , 1996, Biochemical and biophysical research communications.

[110]  D. Harrison,et al.  Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[111]  T. Haas,et al.  The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration. , 1996, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[112]  J. Gutteridge,et al.  Lipid peroxidation and antioxidants as biomarkers of tissue damage. , 1995, Clinical chemistry.

[113]  M. Labow,et al.  Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. , 1995, Development.

[114]  M. Cybulsky,et al.  Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. , 1995, Genes & development.

[115]  H. Augustin,et al.  Differentiation of endothelial cells: Analysis of the constitutive and activated endothelial cell phenotypes , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[116]  M. Davies,et al.  The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis , 1993, The Journal of pathology.

[117]  H. Loetscher,et al.  Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55 , 1993, The Journal of experimental medicine.