Reduced bone morphogenetic protein receptor 2 (BMPR2) expression in patients with pulmonary arterial hypertension (PAH) can impair pulmonary arterial EC (PAEC) function. This can adversely affect EC survival and promote SMC proliferation. We hypothesized that interventions to normalize expression of genes that are targets of BMPR2 signaling could restore PAEC function and prevent or reverse PAH. Here we have characterized, in human PAECs, a BMPR2-mediated transcriptional complex between PPARγ and β-catenin and shown that disruption of this complex impaired BMP-mediated PAEC survival. Using whole genome-wide ChIP-Chip promoter analysis and gene expression microarrays, we delineated PPARγ/β-catenin–dependent transcription of target genes including APLN, which encodes apelin. We documented reduced PAEC expression of apelin in PAH patients versus controls. In cell culture experiments, we showed that apelin-deficient PAECs were prone to apoptosis and promoted pulmonary arterial SMC (PASMC) proliferation. Conversely, we established that apelin, like BMPR2 ligands, suppressed proliferation and induced apoptosis of PASMCs. Consistent with these functions, administration of apelin reversed PAH in mice with reduced production of apelin resulting from deletion of PPARγ in ECs. Taken together, our findings suggest that apelin could be effective in treating PAH by rescuing BMPR2 and PAEC dysfunction.
Tero-Pekka Alastalo, Molong Li, Vinicio de Jesus Perez, David Pham, Hirofumi Sawada, Jordon K. Wang, Minna Koskenvuo, Lingli Wang, Bruce A. Freeman, Howard Y. Chang, Marlene Rabinovitch
Title and authors | Publication | Year |
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The biased apelin receptor agonist, MM07, reverses Sugen/hypoxia-induced pulmonary arterial hypertension as effectively as the endothelin antagonist macitentan
Williams TL, Nyimanu D, Kuc RE, Foster R, Glen RC, Maguire JJ, Davenport AP |
Frontiers in pharmacology | 2024 |
The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases
Hu P, Du Y, Xu Y, Ye P, Xia J |
Frontiers in Cardiovascular Medicine | 2024 |
Apelin-13 modulates the endometrial transcriptome of the domestic pig during implantation
Dobrzyn K, Kiezun M, Kopij G, Zarzecka B, Gudelska M, Kisielewska K, Zaobidna E, Makowczenko KG, Dall\u2019Aglio C, Kamiński T, Smolińska N |
BMC Genomics | 2024 |
Editorial: Pulmonary hypertension: from bench to bedside
Foris V, Olschewski A |
Frontiers in physiology | 2024 |
Exploring the pathogenesis of pulmonary vascular disease
Ejikeme C, Safdar Z |
Frontiers in Medicine | 2024 |
mTOR in the Development of Hypoxic Pulmonary Hypertension Associated with Cardiometabolic Risk Factors.
Flores K, Almeida C, Arriaza K, Pena E, El Alam S |
International journal of molecular sciences | 2024 |
Pathology and pathobiology of pulmonary hypertension: current insights and future directions.
Guignabert C, Aman J, Bonnet S, Dorfmüller P, Olschewski AJ, Pullamsetti S, Rabinovitch M, Schermuly RT, Humbert M, Stenmark KR |
The European respiratory journal | 2024 |
Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling.
Qi RQ, Chen YF, Cheng J, Song JW, Chen YH, Wang SY, Liu Y, Yan KX, Liu XY, Li J, Zhong JC |
Molecular medicine (Cambridge, Mass.) | 2024 |
Apelin-13 as a novel diagnostic laboratory biomarker in thromboembolic disorders: a review of literature with prospective insights
Karimi M, Shirsalimi N, Sedighi E |
International Journal of Emergency Medicine | 2024 |
Apelin-17 to diagnose idiopathic pulmonary arterial hypertension: A biomarker study
Foris V, Kovacs G, Avian A, Bálint Z, Douschan P, Ghanim B, Klepetko W, Olschewski A, Olschewski H |
Frontiers in physiology | 2023 |
Transcription factors in the pathogenesis of pulmonary arterial hypertension—Current knowledge and therapeutic potential
Körbelin J, Klein J, Matuszcak C, Runge J, Harbaum L, Klose H, Hennigs JK |
Frontiers in Cardiovascular Medicine | 2023 |
Estrogen Receptor-α Exerts Endothelium-Protective Effects and Attenuates Pulmonary Hypertension
Frump AL, Yakubov B, Walts A, Fisher A, Cook T, Chesler NC, Lahm T |
American journal of respiratory cell and molecular biology | 2023 |
Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.
Wang L, Moonen JR, Cao A, Isobe S, Li CG, Tojais NF, Taylor S, Marciano DP, Chen PI, Gu M, Li D, Harper RL, El-Bizri N, Kim YM, Stankunas K, Rabinovitch M |
Circulation research | 2023 |
Are Senolytic Agents Guilty of Overkill or Inappropriate Age Discrimination?
Rabinovitch M |
Circulation | 2023 |
Transcription factors and potential therapeutic targets for pulmonary hypertension
Yang L, Wan N, Gong F, Wang X, Feng L, Liu G |
Frontiers in Cell and Developmental Biology | 2023 |
GATA6 coordinates cross-talk between BMP10 and oxidative stress axis in pulmonary arterial hypertension
Toyama T, Kudryashova TV, Ichihara A, Lenna S, Looney A, Shen Y, Jiang L, Teos L, Avolio T, Lin D, Kaplan U, Marden G, Dambal V, Goncharov D, Delisser H, Lafyatis R, Seta F, Goncharova EA, Trojanowska M |
Scientific Reports | 2023 |
Age‐Associated Changes in Endothelial Transcriptome and Epigenetic Landscapes Correlate With Elevated Risk of Cerebral Microbleeds
Mohan K, Gasparoni G, Salhab A, Orlich MM, Geffers R, Hoffmann S, Adams RH, Walter J, Nordheim A |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2023 |
Fatty acid nitroalkenes – Multi-target agents for the treatment of sickle cell disease
Chowdhury FA, Colussi N, Sharma M, Wood KC, Xu JZ, Freeman BA, Schopfer FJ, Straub AC |
Redox Biology | 2023 |
Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension
Isobe S, Nair RV, Kang HY, Wang L, Moonen JR, Shinohara T, Cao A, Taylor S, Otsuki S, Marciano DP, Harper RL, Adil MS, Zhang C, Lago-Docampo M, Körbelin J, Engreitz JM, Snyder MP, Rabinovitch M |
Nature Communications | 2023 |
Mechanism of Interaction between hsa_circ_0002854 and MAPK1 Protein in PM2.5-Induced Apoptosis of Human Bronchial Epithelial Cells
Hong J, Tan Y, Wang Y, Wang H, Li C, Jin W, Wu Y, Ni D, Peng X |
Toxics | 2023 |
Adipokines in pulmonary hypertension: angels or demons?
Jia Q, Ouyang Y, Yang Y, Yao S, Chen X, Hu Z |
Heliyon | 2023 |
Targeting the apelin system for the treatment of cardiovascular diseases
Chapman FA, Maguire JJ, Newby DE, Davenport AP, Dhaun N |
Cardiovascular Research | 2023 |
Therapeutic Approaches for Treating Pulmonary Arterial Hypertension by Correcting Imbalanced TGF-β Superfamily Signaling
P Andre, S Joshi, S Briscoe, M Alexander, G Li, R Kumar |
Frontiers in Medicine | 2022 |
Mechanisms of pulmonary vascular dysfunction in pulmonary hypertension and implications for novel therapies
H Christou, R Khalil |
American journal of physiology. Heart and circulatory physiology | 2022 |
Development of vascular disease models to explore disease causation and pathomechanisms of rare vascular diseases
R Harper, E Ferrante, M Boehm |
Seminars in Immunopathology | 2022 |
MicroRNAs in Pulmonary Hypertension, from Pathogenesis to Diagnosis and Treatment.
Xu J, Linneman J, Zhong Y, Yin H, Xia Q, Kang K, Gou D |
Biomolecules | 2022 |
Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
Zhang Q, Liu Y, Li J, Wang J, Liu C |
Bioactive Materials | 2022 |
Metabolic reprogramming: A novel metabolic model for pulmonary hypertension.
Liu X, Zhang L, Zhang W |
Frontiers in Cardiovascular Medicine | 2022 |
Non-Muscle MLCK Contributes to Endothelial Cell Hyper-Proliferation through the ERK Pathway as a Mechanism for Vascular Remodeling in Pulmonary Hypertension
Anis M, Gonzales J, Halstrom R, Baig N, Humpal C, Demeritte R, Epshtein Y, Jacobson JR, Fraidenburg DR |
International journal of molecular sciences | 2022 |
Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and Ca2+ signaling
Balistrieri A, Makino A, Yuan JX |
Physiological reviews | 2022 |
Tm4sf1-marked Endothelial Subpopulation Is Dysregulated in Pulmonary Arterial Hypertension
Hong J, Wong B, Huynh C, Tang B, Ruffenach G, Li M, Umar S, Yang X, Eghbali M |
American journal of respiratory cell and molecular biology | 2022 |
17β-estradiol and estrogen receptor-α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin
Andrea L Frump, Marjorie E Albrecht, Bakhtiyor Yakubov, Sandra Breuils Bonnet, Valerie Nadeau, Eve Tremblay, Francois Potus, Junichi Omura, Todd Cook, Amanda Fisher, Brooke E. Rodriguez, R. Dale Brown, Kurt R Stenmark, C. Dustin Rubinstein, Kathy Krentz, Diana M Tabima, Rongbo Li, Xin Sun, Naomi C. Chesler, Steeve Provencher, Sebastien Bonnet, Tim Lahm |
Journal of Clinical Investigation | 2021 |
Monocyte released HERV-K dUTPase engages TLR4 and MCAM causing endothelial mesenchymal transition
Shoichiro Otsuki, Toshie Saito, Shalina Taylor, Dan Li, Jan-Renier Moonen, David P. Marciano, Rebecca L Harper, Aiqin Cao, Lingli Wang, Maria Eugenia Ariza, Marlene Rabinovitch |
JCI Insight | 2021 |
Endothelial cells in the pathogenesis of pulmonary arterial hypertension
CE Evans, ND Cober, Z Dai, DJ Stewart, YY Zhao |
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | 2021 |
High-fat diet attenuates the improvement of hypoxia-induced pulmonary hypertension in mice during reoxygenation
K Sugimoto, T Yokokawa, T Misaka, T Kaneshiro, A Yoshihisa, K Nakazato, Y Takeishi |
BMC Cardiovascular Disorders | 2021 |
iPSC–endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension
M Gu, M Donato, M Guo, N Wary, Y Miao, S Mao, T Saito, S Otsuki, L Wang, RL Harper, S Sa, P Khatri, M Rabinovitch |
Science Translational Medicine | 2021 |
Endothelial Dec1-PPARγ Axis Impairs Proliferation and Apoptosis Homeostasis Under Hypoxia in Pulmonary Arterial Hypertension
X Li, C Liu, W Qi, Q Meng, H Zhao, Z Teng, R Xu, X Wu, F Zhu, Y Qin, M Zhao, F Xu, M Xia |
Frontiers in Cell and Developmental Biology | 2021 |
Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10
NE Owen, D Nyimanu, RE Kuc, PD Upton, NW Morrell, GJ Alexander, JJ Maguire, AP Davenport |
Peptides | 2021 |
The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis In Vitro and Induces Vasodilatation Without Desensitisation In Vivo
C Read, D Nyimanu, P Yang, RE Kuc, TL Williams, CM Fitzpatrick, R Foster, RC Glen, JJ Maguire, AP Davenport |
Frontiers in pharmacology | 2021 |
Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes
DS Kostyunina, P McLoughlin |
Antioxidants | 2021 |
Vascular Endothelial Cells: Heterogeneity and Targeting Approaches
JK Hennigs, C Matuszcak, M Trepel, J Körbelin |
Cells | 2021 |
Imbalanced Activation of Wnt-/β-Catenin-Signaling in Liver Endothelium Alters Normal Sinusoidal Differentiation
PS Koch, K Sandorski, J Heil, CD Schmid, SW Kürschner, J Hoffmann, M Winkler, T Staniczek, C de la Torre, C Sticht, K Schledzewski, MM Taketo, FA Trogisch, J Heineke, C Géraud, S Goerdt, V Olsavszky |
Frontiers in physiology | 2021 |
Extracellular matrix degradation pathways and fatty acid metabolism regulate distinct pulmonary vascular cell types in pulmonary arterial hypertension
S Mumby, F Perros, C Hui, BL Xu, W Xu, V Elyasigomari, A Hautefort, G Manaud, M Humbert, KF Chung, SJ Wort, IM Adcock |
Pulmonary circulation | 2021 |
Activation of Transcription Factor 4 in Dendritic Cells Controls Th1/Th17 Responses and Autoimmune Neuroinflammation
I Manoharan, D Swafford, A Shanmugam, N Patel, PD Prasad, M Thangaraju, S Manicassamy |
Journal of immunology (Baltimore, Md. : 1950) | 2021 |
Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis
AS Wahba, ME Ibrahim, DM Abo-elmatty, ET Mehanna |
Journal of Personalized Medicine | 2021 |
Exploring New Therapeutic Pathways in Pulmonary Hypertension. Metabolism, Proliferation, and Personalized Medicine
MP George, MT Gladwin, BB Graham |
American journal of respiratory cell and molecular biology | 2020 |
Micro RNA ‐483 amelioration of experimental pulmonary hypertension
J Zhang, Y He, X Yan, S Chen, M He, Y Lei, J Zhang, B Gongol, M Gu, Y Miao, L Bai, X Cui, X Wang, Y Zhang, F Fan, Z Li, Y Shen, CH Chou, HD Huang, A Malhotra, M Rabinovitch, ZC Jing, JY Shyy |
EMBO Molecular Medicine | 2020 |
Upregulation of miR-335-3p by NF-κB Transcriptional Regulation Contributes to the Induction of Pulmonary Arterial Hypertension via APJ during Hypoxia
J Fan, X Fan, H Guang, X Shan, Q Tian, F Zhang, R Chen, F Ye, H Quan, H Zhang, L Ding, Z Gan, F Xue, Y Wang, S Mao, L Hu, Y Gong |
International journal of biological sciences | 2020 |
Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension
A Keshavarz, H Kadry, A Alobaida, F Ahsan |
Expert Opinion on Drug Delivery | 2020 |
Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies
O Bondareva, BN Sheikh |
International journal of molecular sciences | 2020 |
Endothelial Twist1-PDGFB signaling mediates hypoxia-induced proliferation and migration of αSMA-positive cells
A Mammoto, K Hendee, M Muyleart, T Mammoto |
Scientific Reports | 2020 |
Obesity, estrogens and adipose tissue dysfunction – implications for pulmonary arterial hypertension
KM Mair, R Gaw, MR MacLean |
Pulmonary circulation | 2020 |
PPARγ-p53-Mediated Vasculoregenerative Program to Reverse Pulmonary Hypertension
JK Hennigs, A Cao, CG Li, M Shi, J Mienert, K Miyagawa, J Körbelin, DP Marciano, PI Chen, M Roughley, MV Elliott, RL Harper, MA Bill, J Chappell, JR Moonen, I Diebold, L Wang, MP Snyder, M Rabinovitch |
Circulation research | 2020 |
Apelin signaling drives vascular endothelial cells toward a pro-angiogenic state
CS Helker, J Eberlein, K Wilhelm, T Sugino, J Malchow, A Schuermann, S Baumeister, HB Kwon, HM Maischein, M Potente, W Herzog, DY Stainier |
eLife | 2020 |
Advances in therapeutic peptides targeting G protein-coupled receptors
AP Davenport, CC Scully, C de Graaf, AJ Brown, JJ Maguire |
Nature Reviews Drug Discovery | 2020 |
Apelin/APJ system: an emerging therapeutic target for respiratory diseases
J Yan, A Wang, J Cao, L Chen |
Cellular and Molecular Life Sciences | 2020 |
DNA Damage and Repair in Pulmonary Arterial Hypertension
S Sharma, MA Aldred |
Genes & development | 2020 |
Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function
C Kuiper-Makris, D Zanetti, C Vohlen, L Fahle, M Müller, M Odenthal, U Felderhoff-Müser, J Dötsch, MA Alcazar |
Scientific Reports | 2020 |
Apelin/Elabela-APJ: a novel therapeutic target in the cardiovascular system
Liu W, Yan J, Pan W, Tang M |
Annals of translational medicine | 2020 |
Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1–Mediated Metabolic and Epigenetic Changes
K Miyagawa, M Shi, PI Chen, JK Hennigs, Z Zhao, M Wang, CG Li, T Saito, S Taylor, S Sa, A Cao, L Wang, MP Snyder, M Rabinovitch |
Circulation research | 2019 |
Cell Death in the Lung: The Apoptosis–Necroptosis Axis
M Sauler, IS Bazan, PJ Lee |
Annual Review of Physiology | 2019 |
The Search for Disease-Modifying Therapies in Pulmonary Hypertension
CS Woodcock, SY Chan |
Journal of cardiovascular pharmacology and therapeutics | 2019 |
PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis
CG Li, C Mahon, NM Sweeney, E Verschueren, V Kantamani, D Li, JK Hennigs, DP Marciano, I Diebold, O Abu-Halawa, M Elliott, S Sa, F Guo, L Wang, A Cao, C Guignabert, J Sollier, NP Nickel, M Kaschwich, KA Cimprich, M Rabinovitch |
Cell Reports | 2019 |
International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand
C Read, D Nyimanu, TL Williams, DJ Huggins, P Sulentic, RG Macrae, P Yang, RC Glen, JJ Maguire, AP Davenport, EH Ohlstein |
Pharmacological reviews | 2019 |
The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders
E Marsault, C LlorensCortes, X Iturrioz, HJ Chun, O Lesur, GY Oudit, M AugerMessier |
Annals of the New York Academy of Sciences | 2019 |
Key inflammatory pathways underlying vascular remodeling in pulmonary hypertension
EM Berghausen, L Feik, M Zierden, M Vantler, S Rosenkranz |
Herz | 2019 |
A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension
P Yang, C Read, RE Kuc, D Nyimanu, TL Williams, A Crosby, G Buonincontri, M Southwood, SJ Sawiak, RC Glen, NW Morrell, AP Davenport, JJ Maguire |
British Journal of Pharmacology | 2019 |
APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target
H Chen, CC Wong, D Liu, MY Go, B Wu, S Peng, M Kuang, N Wong, J Yu |
Theranostics | 2019 |
Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor
D Nyimanu, RE Kuc, TL Williams, M Bednarek, P Ambery, L Jermutus, JJ Maguire, AP Davenport |
Peptides | 2019 |
BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFβ responses and altered cell mechanics
C Hiepen, J Jatzlau, S Hildebrandt, B Kampfrath, M Goktas, A Murgai, JL Camacho, R Haag, C Ruppert, G Sengle, EA Cavalcanti-Adam, KG Blank, P Knaus, MC Mullins |
PLoS Biology | 2019 |
GPCRs in pulmonary arterial hypertension: tipping the balance: GPCRs in pulmonary hypertension
J Iyinikkel, F Murray |
British Journal of Pharmacology | 2018 |
Emerging therapeutics in pulmonary hypertension
MK Hensley, A Levine, MT Gladwin, YC Lai |
American journal of physiology. Lung cellular and molecular physiology | 2018 |
Emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension
AL Frump, S Bonnet, VA de Jesus Perez, T Lahm |
American journal of physiology. Lung cellular and molecular physiology | 2018 |
The Role of Neutrophils and Neutrophil Elastase in Pulmonary Arterial Hypertension
S Taylor, O Dirir, RT Zamanian, M Rabinovitch, AA Thompson |
Frontiers in Medicine | 2018 |
A novel piperidine identified by stem cell based screening attenuates pulmonary arterial hypertension via regulating BMP2 and PTGS2 levels
Y Xing, S Zhao, Q Wei, S Gong, X Zhao, F Zhou, R AI-Lamki, D Ortmann, M Du, R Pedersen, G Shang, S Si, NW Morrell, J Yang |
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | 2018 |
BMPR2 mutations and endothelial dysfunction in pulmonary arterial hypertension (2017 Grover Conference Series)
A Frump, A Prewitt, MP de Caestecker |
Pulmonary circulation | 2018 |
Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension
L Brash, GD Barnes, MJ Brewis, AC Church, SJ Gibbs, LS Howard, G Jayasekera, MK Johnson, N McGlinchey, J Onorato, J Simpson, C Stirrat, S Thomson, G Watson, MR Wilkins, C Xu, DJ Welsh, DE Newby, AJ Peacock |
JACC: Basic to Translational Science | 2018 |
The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension
G Viswanathan, A Mamazhakypov, RT Schermuly, S Rajagopal |
Frontiers in Cardiovascular Medicine | 2018 |
Overexpression of apelin in Wharton’ jelly mesenchymal stem cell reverses insulin resistance and promotes pancreatic β cell proliferation in type 2 diabetic rats
LR Gao, NK Zhang, Y Zhang, Y Chen, L Wang, Y Zhu, HH Tang |
Stem Cell Research & Therapy | 2018 |
Gremlin 1 blocks vascular endothelial growth factor signaling in the pulmonary microvascular endothelium
SC Rowan, L Piouceau, J Cornwell, L Li, P McLoughlin |
Pulmonary circulation | 2018 |
Emerging Metabolic Therapies in Pulmonary Arterial Hypertension
L Harvey, S Chan |
Journal of Clinical Medicine | 2017 |
Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin’s glucose-lowering effects
C Hwangbo, J Wu, I Papangeli, T Adachi, B Sharma, S Park, L Zhao, H Ju, G Go, G Cui, M Inayathullah, JK Job, J Rajadas, SL Kwei, MO Li, AR Morrison, T Quertermous, A Mani, K Red-Horse, HJ Chun |
Science Translational Medicine | 2017 |
Baicalin attenuates monocrotaline-induced pulmonary hypertension through bone morphogenetic protein signaling pathway
Z Zhang, L Zhang, C Sun, F Kong, J Wang, Q Xin, W Jiang, K Li, O Chen, Y Luan |
Oncotarget | 2017 |
[Pyr1]Apelin-13(1–12) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr1]Apelin-13
P Yang, RE Kuc, AL Brame, A Dyson, M Singer, RC Glen, J Cheriyan, IB Wilkinson, AP Davenport, JJ Maguire |
Frontiers in neuroscience | 2017 |
Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin
SL Gonidec, C Chaves-Almagro, Y Bai, HJ Kang, A Smith, E Wanecq, , H Prats, B Knibiehler, BL Roth, LS Barak, MG Caron, P Valet, Y Audigier, B Masri |
The FASEB Journal | 2017 |
The Role of the Apelin/APJ System in the Regulation of Liver Disease
WD Chen, YD Wang, X Lv, J Kong |
Frontiers in pharmacology | 2017 |
Isolated heart model demonstrates evidence of contractile and diastolic dysfunction in right ventricles from rats with sugen/hypoxia‐induced pulmonary hypertension
EM NetoNeves, AL Frump, A Vayl, JA Kline, T Lahm |
Physiological Reports | 2017 |
Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial HypertensionClinical Perspective
P Yang, C Read, RE Kuc, G Buonincontri, M Southwood, R Torella, PD Upton, A Crosby, SJ Sawiak, TA Carpenter, RC Glen, NW Morrell, JJ Maguire, AP Davenport |
Circulation | 2017 |
Suppression of the expression of hypoxia-inducible factor-1α by RNA interference alleviates hypoxia-induced pulmonary hypertension in adult rats
Y Li, B Shi, L Huang, X Wang, X Yu, B Guo, W Ren |
International journal of molecular medicine | 2016 |
Loss of PPAR in endothelial cells leads to impaired angiogenesis
S Vattulainen-Collanus, O Akinrinade, M Li, M Koskenvuo, CG Li, SP Rao, VJ Perez, K Yuan, H Sawada, JW Koskenvuo, C Alvira, M Rabinovitch, TP Alastalo |
Journal of cell science | 2016 |
In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target SlugCLINICAL PERSPECTIVE
RK Hopper, JR Moonen, I Diebold, A Cao, CJ Rhodes, NF Tojais, JK Hennigs, M Gu, L Wang, M Rabinovitch |
Circulation | 2016 |
Cardiac action of the first G protein biased small molecule apelin agonist
C Read, CM Fitzpatrick, P Yang, RE Kuc, JJ Maguire, RC Glen, RE Foster, AP Davenport |
Biochemical Pharmacology | 2016 |
Independence Day: Separating Right Ventricular Function From Pulmonary Arterial Hypertension in Systemic Sclerosis
BA Maron |
Circulation | 2016 |
The emerging role of epigenetics in pulmonary arterial hypertension: an important avenue for clinical trials (2015 Grover Conference Series)
JH Huston, JJ Ryan |
Pulmonary circulation | 2016 |
Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers
M Gu, NY Shao, S Sa, D Li, V Termglinchan, M Ameen, I Karakikes, G Sosa, F Grubert, J Lee, A Cao, S Taylor, Y Ma, Z Zhao, J Chappell, R Hamid, ED Austin, JD Gold, JC Wu, MP Snyder, M Rabinovitch |
Cell Stem Cell | 2016 |
Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms.
Villacorta L, Gao Z, Schopfer FJ, Freeman BA, Chen YE |
2016 | |
儿童先天性心脏病血清Apelin水平与肺动脉压关系的初步探讨
|
2016 | |
Molecular pathogenesis and current pathology of pulmonary hypertension
VA de Perez |
Heart Failure Reviews | 2015 |
-Catenin Promotes Regulatory T-cell Responses in Tumors by Inducing Vitamin A Metabolism in Dendritic Cells
Y Hong, I Manoharan, A Suryawanshi, T Majumdar, ML Angus-Hill, PA Koni, B Manicassamy, AL Mellor, DH Munn, S Manicassamy |
Cancer research | 2015 |
BMPR2 Preserves Mitochondrial Function and DNA during Reoxygenation to Promote Endothelial Cell Survival and Reverse Pulmonary Hypertension
I Diebold, JK Hennigs, K Miyagawa, CG Li, NP Nickel, M Kaschwich, A Cao, L Wang, S Reddy, PI Chen, K Nakahira, MA Alcazar, RK Hopper, L Ji, BJ Feldman, M Rabinovitch |
Cell Metabolism | 2015 |
Elafin Reverses Pulmonary Hypertension via Caveolin-1–Dependent Bone Morphogenetic Protein Signaling
NP Nickel, E Spiekerkoetter, M Gu, CG Li, H Li, M Kaschwich, I Diebold, JK Hennigs, KY Kim, K Miyagawa, L Wang, A Cao, S Sa, X Jiang, RW Stockstill, MR Nicolls, RT Zamanian, RD Bland, M Rabinovitch |
American journal of respiratory and critical care medicine | 2015 |
PPARγ Ligands Attenuate Hypoxia-Induced Proliferation in Human Pulmonary Artery Smooth Muscle Cells through Modulation of MicroRNA-21
DE Green, TC Murphy, BY Kang, CD Searles, CM Hart, J West |
PloS one | 2015 |
Raf/ERK drives the proliferative and invasive phenotype of BMPR2-silenced pulmonary artery endothelial cells
KS Awad, JM Elinoff, S Wang, S Gairhe, GA Ferreyra, R Cai, J Sun, MA Solomon, RL Danner |
American journal of physiology. Lung cellular and molecular physiology | 2015 |
Effects of apelin on the cardiovascular system
A Folino, PG Montarolo, M Samaja, R Rastaldo |
Heart Failure Reviews | 2015 |
Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system
P Yang, JJ Maguire, AP Davenport |
Trends in Pharmacological Sciences | 2015 |
The Endothelial Transcription Factor ERG Promotes Vascular Stability and Growth through Wnt/β-Catenin Signaling
GM Birdsey, AV Shah, N Dufton, LE Reynolds, L Osuna Almagro, Y Yang, IM Aspalter, ST Khan, JC Mason, E Dejana, B Göttgens, K Hodivala-Dilke, H Gerhardt, RH Adams, AM Randi |
Developmental Cell | 2015 |
Design, Characterization, and First-In-Human Study of the Vascular Actions of a Novel Biased Apelin Receptor Agonist
AL Brame, JJ Maguire, P Yang, A Dyson, R Torella, J Cheriyan, M Singer, RC Glen, IB Wilkinson, AP Davenport |
Hypertension | 2015 |
Elafin in Pulmonary Arterial Hypertension. Beyond Targeting Elastases
HJ Chun, PB Yu |
American journal of respiratory and critical care medicine | 2015 |
RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension
CJ Rhodes, H Im, A Cao, JK Hennigs, L Wang, S Sa, PI Chen, NP Nickel, K Miyagawa, RK Hopper, NF Tojais, CG Li, M Gu, E Spiekerkoetter, Z Xian, R Chen, M Zhao, M Kaschwich, PA Rosario, D Bernstein, RT Zamanian, JC Wu, MP Snyder, M Rabinovitch |
American journal of respiratory and critical care medicine | 2015 |
Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension
Thomas Bertero, Yu Lu, Sofia Annis, Andrew Hale, Balkrishen Bhat, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Sara O. Vargas, Brian B. Graham, Rahul Kumar, Stephen M. Black, Sohrab Fratz, Jeffrey R. Fineman, James D. West, Kathleen J. Haley, Aaron B. Waxman, B. Nelson Chau, Katherine A. Cottrill, Stephen Y. Chan |
Journal of Clinical Investigation | 2014 |
Restoration of Impaired Endothelial MEF2 Function Rescues Pulmonary Arterial Hypertension
J Kim, C Hwangbo, X Hu, Y Kang, I Papangeli, D Mehrotra, H Park, DL McLean, H Ju, SA Comhair, SC Erzurum, HJ Chun |
Circulation | 2014 |
Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension
H Sawada, T Saito, NP Nickel, TP Alastalo, JP Glotzbach, R Chan, L Haghighat, G Fuchs, M Januszyk, A Cao, YJ Lai, VJ Perez, YM Kim, L Wang, PI Chen, E Spiekerkoetter, Y Mitani, GC Gurtner, P Sarnow, M Rabinovitch |
Journal of Experimental Medicine | 2014 |
The myriad essential roles of microRNAs in cardiovascular homeostasis and disease
RL Neppl, DZ Wang |
Genes & Diseases | 2014 |
Endothelium as a gatekeeper of fatty acid transport
D Mehrotra, J Wu, I Papangeli, HJ Chun |
Trends in Endocrinology & Metabolism | 2014 |
Inflammation and Immunity in the Pathogenesis of Pulmonary Arterial Hypertension
M Rabinovitch, C Guignabert, M Humbert, MR Nicolls |
Circulation research | 2014 |
Targeting the Wnt signaling pathways in pulmonary arterial hypertension
VJ Perez, K Yuan, TP Alastalo, E Spiekerkoetter, M Rabinovitch |
Drug Discovery Today | 2014 |
The MicroRNA-130/301 Family Controls Vasoconstriction in Pulmonary Hypertension
T Bertero, K Cottrill, A Krauszman, Y Lu, S Annis, A Hale, B Bhat, AB Waxman, BN Chau, WM Kuebler, SY Chan |
The Journal of biological chemistry | 2014 |
Apelin-APJ Signaling: a Potential Therapeutic Target for Pulmonary Arterial Hypertension
J Kim |
Molecules and Cells | 2014 |
ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease
C Lathen, Y Zhang, J Chow, M Singh, G Lin, V Nigam, YA Ashraf, JX Yuan, IM Robbins, PA Thistlethwaite |
Circulation | 2014 |
Apelin inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia
H Zhang, Y Gong, Z Wang, L Jiang, R Chen, X Fan, H Zhu, L Han, X Li, J Xiao, X Kong |
Journal of Cellular and Molecular Medicine | 2014 |
The role of BMPs in endothelial cell function and dysfunction
LA Dyer, X Pi, C Patterson |
Trends in Endocrinology & Metabolism | 2014 |
Diversity Is in My Veins: Role of Bone Morphogenetic Protein Signaling During Venous Morphogenesis in Zebrafish Illustrates the Heterogeneity Within Endothelial Cells
JD Kim, HW Lee, SW Jin |
Arteriosclerosis, thrombosis, and vascular biology | 2014 |
FK506 Activates BMPR2 Signaling, Rescues Endothelial Dysfunction, Reverses Pulmonary Hypertension
Edda Spiekerkoetter, Xuefei Tian, Jie Cai, Rachel Hopper, Deepti Sudheendra, Caiyun Grace Li, Nesrine El-Bizri, Hirofumi Sawada, Roxanna Haghighat, Roshelle Chan, Leila Haghighat, Vinicio de Jesus Perez, Lingli Wang, Sushma Reddy, Mingming Zhao, Daniel Bernstein, David Solow-Cordero, Philip A. Beachy, Thomas Wandless, Peter Ten Dijke, Marlene Rabinovitch |
Journal of Clinical Investigation | 2013 |
Loss of Apelin exacerbates myocardial infarction adverse remodeling and ischemia-reperfusion injury: therapeutic potential of synthetic Apelin analogues
W Wang, SM McKinnie, VB Patel, G Haddad, Z Wang, P Zhabyeyev, SK Das, R Basu, B McLean, V Kandalam, JM Penninger, Z Kassiri, JC Vederas, AG Murray, GY Oudit |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2013 |
Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension
W Tian, X Jiang, R Tamosiuniene, YK Sung, J Qian, G Dhillon, L Gera, L Farkas, M Rabinovitch, RT Zamanian, M Inayathullah, M Fridlib, J Rajadas, M Peters-Golden, NF Voelkel, MR Nicolls |
Science Translational Medicine | 2013 |
Anticipated classes of new medications and molecular targets for pulmonary arterial hypertension
NW Morrell, SL Archer, A Defelice, S Evans, M Fiszman, T Martin, M Saulnier, M Rabinovitch, R Schermuly, D Stewart, H Truebel, G Walker, KR Stenmark |
Pulmonary circulation | 2013 |
Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts
M Fakhry, E Hamade, B Badran, R Buchet, D Magne |
World journal of stem cells | 2013 |
Endothelial Indoleamine 2,3-Dioxygenase Protects against Development of Pulmonary Hypertension
Y Xiao, H Christou, L Liu, G Visner, SA Mitsialis, S Kourembanas, H Liu |
American journal of respiratory and critical care medicine | 2013 |
Signal transduction in the development of pulmonary arterial hypertension
S Malenfant, AS Neyron, R Paulin, F Potus, J Meloche, S Provencher, S Bonnet |
Pulmonary circulation | 2013 |
Hypoxia mediates mutual repression between microRNA-27a and PPARγ in the pulmonary vasculature
BY Kang, KK Park, DE Green, KM Bijli, CD Searles, RL Sutliff, CM Hart |
PloS one | 2013 |
Decreased apelin and apelin-receptor expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia
AD Hofmann, F Friedmacher, H Takahashi, M Hunziker, JH Gosemann, P Puri |
Pediatric Surgery International | 2013 |
Effects of PPAR γ Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats
I Dovinová, M Barancik, M Majzunova, S Zorad, L Gajdosechová, L Gresová, S Cacanyiova, F Kristek, P Balis, JY Chan |
PPAR Research | 2013 |
Integrating molecular genetics and systems approaches to pulmonary vascular diseases
MW Geraci |
Pulmonary circulation | 2013 |
New horizons in pulmonary arterial hypertension therapies
Galiè N, Ghofrani AH |
European Respiratory Review | 2013 |
Molecular pathogenesis of pulmonary arterial hypertension
Marlene Rabinovitch |
Journal of Clinical Investigation | 2012 |
A process-based review of mouse models of pulmonary hypertension
M Das, J Fessel, H Tang, J West |
Pulmonary circulation | 2012 |
Loss of Adenomatous Poliposis Coli-α3 Integrin Interaction Promotes Endothelial Apoptosis in Mice and Humans
VA de Jesus Perez, K Yuan, ME Orcholski, H Sawada, M Zhao, CG Li, NF Tojais, N Nickel, V Rajagopalan, E Spiekerkoetter, L Wang, R Dutta, D Bernstein, M Rabinovitch |
Circulation research | 2012 |
Targeting the ACE2 and Apelin Pathways Are Novel Therapies for Heart Failure: Opportunities and Challenges
SM Kazemi-Bajestani, VB Patel, W Wang, GY Oudit |
Cardiology Research and Practice | 2012 |
An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension
J Kim, Y Kang, Y Kojima, JK Lighthouse, X Hu, MA Aldred, DL McLean, H Park, SA Comhair, DM Greif, SC Erzurum, HJ Chun |
Nature Medicine | 2012 |
Comprehensive Physiology
R Terjung |
Comprehensive Physiology | 2011 |
Apelin and pulmonary hypertension
CU Andersen, O Hilberg, S Mellemkjær, JE Nielsen-Kudsk, U Simonsen |
Pulmonary circulation | 2011 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |