Plecitá-Hlavatá L, Tauber J, Li M, Zhang H, Flockton AR, Pullamsetti SS, Chelladurai P, D'alessandro A, El Kasmi KC, Ježek P, Stenmark KR.Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension.Am J Respir Cell Mol Biol. 2015 Dec 23.
Using Genetics, Epigenetics And Small Molecules To Reverse Metabolic Reprogramming In Adventitia Fibroblasts For Pulmonary Hypertension Therapy.
H Zhang, D Wang, M Li, L Plecita, A D'alessandro, S Riddle, BA McKeon, ...
B53. PHOUND IN TRANSLATION, A3895-A3895
Functional Reprogramming Of Macrophages Through Targeted Inhibition Of Metabolic Pathways As A Strategy To Promote Anti-Inflammatory Signaling In Pulmonary Hypertension.
K EL Kasmi, S Riddle, M Li, A D’Alessandro, H Zhang, BA McKeon, ...
D26. I'M ON FIRE-INFLAMMATION IN PULMONARY VASCULAR DISEASE, A6585-A6585
Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1. Li M, Riddle S, Zhang H, D'Alessandro A, Flockton A, Serkova NJ, Hansen KC, Moldvan R, McKeon BA, Frid M, Kumar S, Li H, Liu H, Caanovas A, Medrano JF, Thomas MG, Iloska D, Plecita-Hlavata L, Jezek P, Pullamsetti S, Fini MA, El Kasmi KC, Zhang Q and Stenmark KR. Metabolic Circulation. 2016;134:1105-1121.
Plecitá-Hlavatá L, D'alessandro A, El Kasmi K, Li M, Zhang H, Ježek P, Stenmark KR. Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension. Adv Exp Med Biol. 2017;967:241-260. PubMed PMID: 29047090
Zhang H, Wang D, Li M, Plecitá-Hlavatá L, D'Alessandro A, Tauber J, Riddle S, Kumar S, Flockton A, McKeon BA, Frid MG, Reisz JA, Caruso P, El Kasmi KC, Ježek P, Morrell NW, Hu CJ, Stenmark KR. Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis. Circulation. 2017 Dec 19;136(25):2468-2485. PubMed PMID: 28972001
Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension
Lydie Plecitá-Hlavatá, Angelo D’alessandro, Karim El Kasmi, Min Li, Hui Zhang, Petr Ježek, Kurt R. Stenmark
Caruso P, Dunmore BJ, Schlosser K, Schoors S, Dos Santos C, Perez-Iratxeta C, Lavoie JR, Zhang H, Long L, Flockton AR, Frid MG, Upton PD, D'Alessandro A, Hadinnapola C, Kiskin FN, Taha M, Hurst LA, Ormiston ML, Hata A, Stenmark KR, Carmeliet P, Stewart DJ, Morrell NW. Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2. Circulation. 2017 Dec 19;136(25):2451-2467. PubMed PMID: 28971999
Hallmarks of Pulmonary Hypertension: mesenchymal and inflammatory cell metabolic reprogramming
Angelo D’Alessandro, Karim C. El Kasmi Lydie Plecitá-Hlavatá, Petr Ježek, Min Li, Hui Zhang, Sachin R. Gupte, Kurt R. Stenmark
D'Alessandro A, El Kasmi KC, Plecitá-Hlavatá L, Ježek P, Li M, Zhang H, Gupte SA, Stenmark KR. Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming. Antioxid Redox Signal. 2018 Jan 20;28(3):230-250. PubMed PMID: 28637353
Hui Zhang, Cheng-jun Hu, Min Li, Amanda Flockton, Kurt R Stenmark. The Role of HIFs in Maintaining Pulmonary Artery Fibroblast Phenotypes In Pulmonary Hypertension. Am J Respir Crit Care Med 2017;195:A2264.0
Min Li, Lydie Plecita, Alexandre B Mckeon, Maria Frid, Hui Zhang, Sushil Kumar, Amanda Flockton, Kurt R Stenmark. ROS Production And DNA Instability Of Adventitial Fibroblasts Are Regulated By CtBP1 In Pulmonary Hypertension. Am J Respir Crit Care Med 2017;195:A2262.
Karim C El Kasmi, Maureen J Ostaff, Suzette Riddle, Amanda Flockton, Maria Frid, Sushil Kumar, Brittany A McKeon, Min Li, Radu Moldovan, Hui Zhang, Angelo D'Alessandro, Kurt R Stenmark. Targeting Metabolic Reprogramming In Macrophages Activated By Adventitial Fibroblasts In Pulmonary Hypertension As A New Potential Therapy Approach. Am J Respir Crit Care Med 2017;195:A2266.
Hu CJ, Zhang H, Laux A, Pullamsetti SS, Stenmark KR. Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension. J Physiol. 2018 Jun 19. [Epub ahead of print] PubMed PMID: 29920674
Plecitá-Hlavatá L, D'alessandro A, El Kasmi K, Li M, Zhang H, Ježek P, Stenmark KR. Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension. Adv Exp Med Biol. 2017;967:241-260. PubMed PMID: 29047090
Hu CJ, Poth JM, Zhang H, Flockton A, Laux A, Kumar S, McKeon B, Frid MG, Mouradian G, Li M, Riddle S, Pugliese SC, Brown RD, Wallace EM, Graham BB, Stenmark KR. Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension. Eur Respir J. 2019 Sep 12. [Epub ahead of print] PubMed PMID: 31515405
Zhang H, Wang D, Li M, Plecitá-Hlavatá L, D'Alessandro A, Tauber J, Riddle S, Kumar S, Flockton A, McKeon BA, Frid MG, Reisz JA, Caruso P, El Kasmi KC, Ježek P, Morrell NW, Hu CJ, Stenmark KR. Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis. Circulation. 2017 Dec 19;136(25):2468-2485. PubMed PMID: 28972001
Hu CJ, Zhang H, Laux A, Pullamsetti SS, Stenmark KR. Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension. J Physiol. 2019 Feb;597(4):1103-1119. PubMed PMID: 29920674
Frid MG, McKeon BA, Thurman JM, Maron BA, Li M, Zhang H, Kumar S, Sullivan T, Laskowsky J, Fini MA, Hu S, Tuder RM, Gandjeva A, Wilkins MR, Rhodes CJ, Ghataorhe P, Leopold JA, Wang RS, Holers VM, Stenmark KR. Immunoglobulin-Driven Complement Activation Regulates Pro-Inflammatory Remodeling in Pulmonary Hypertension. Am J Respir Crit Care Med. 2019 Sep 23. [Epub ahead of print] PubMed PMID: 31545648
Caruso P, Dunmore BJ, Schlosser K, Schoors S, Dos Santos C, Perez-Iratxeta C, Lavoie JR, Zhang H, Long L, Flockton AR, Frid MG, Upton PD, D'Alessandro A, Hadinnapola C, Kiskin FN, Taha M, Hurst LA, Ormiston ML, Hata A, Stenmark KR, Carmeliet P, Stewart DJ, Morrell NW. Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2. Circulation. 2017 Dec 19;136(25):2451-2467. PubMed PMID: 28971999
Diseases of Pulmonary Circulation
Therapeutic actions of the histone deacetylase inhibitor vorinostat in a neonatal calf model of hypoxia-induced pulmonary hypertension
Glucose 6-phosphate dehydrogenase controls expression of long non-coding RNAs and protein coding genes by regulating DNA methylation, and contributes to the pathogenesis of chronic hypoxia-induced pulmonary hypertension
The metabolic impact of sildenafil treatment and HDAC inhibitors in pulmonary hypertension
Orchestration of H3K27 Methylation: Mechanisms of the Repression of miR-124 and Therapeutic Implication in Pulmonary hypertension
ROLES OF CHROMATIN STRUCTURE, TRANSCRIPTION FACTORS AND EPIGENETIC REGULATORS IN
PERSISTENTLY ACTIVATED PHENOTYPE OF PH VASCULAR CELLS
D'Alessandro A, El Kasmi KC, Plecitá-Hlavatá L, Ježek P, Li M, Zhang H, Gupte SA, Stenmark KR. Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming. Antioxid Redox Signal. 2018 Jan 20;28(3):230-250. PubMed PMID: 28637353
Glucose 6-phosphate dehydrogenase acts as an epigenetic regulator that plays a role in
controlling expression of long non-coding RNA Meg3 and microRNA-135a:
Implications for the pathogenesis of vascular remodeling and pulmonary hypertension
Zhang H, Brown RD, Stenmark KR, Hu CJ. RNA-Binding Proteins in Pulmonary Hypertension. Int J Mol Sci. 2020 May 26;21(11). PubMed PMID: 32466553
Joshi SR, Kitagawa A, Jacob C, Hashimoto R, Dhagia V, Ramesh A, Zheng C, Zhang H, Jordan A, Waddell I, Leopold J, Hu CJ, McMurtry IF, D'Alessandro A, Stenmark KR, Gupte SA. Hypoxic activation of glucose-6-phosphate dehydrogenase controls the expression of genes involved in the pathogenesis of pulmonary hypertension through the regulation of DNA methylation. Am J Physiol Lung Cell Mol Physiol. 2020 Apr 1;318(4):L773-L786. PubMed PMID: 32159369
Frid MG, McKeon BA, Thurman JM, Maron BA, Li M, Zhang H, Kumar S, Sullivan T, Laskowsky J, Fini MA, Hu S, Tuder RM, Gandjeva A, Wilkins MR, Rhodes CJ, Ghataorhe P, Leopold JA, Wang RS, Holers VM, Stenmark KR. Immunoglobulin-driven Complement Activation Regulates Proinflammatory Remodeling in Pulmonary Hypertension. Am J Respir Crit Care Med. 2020 Jan 15;201(2):224-239. PubMed PMID: 31545648
Applegate TJ, Krafsur GM, Boon JA, Zhang H, Li M, Holt TN, Ambler SK, Abrams BA, Gustafson DL, Bartels K, Garry FB, Stenmark KR, Brown RD. Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension. Front Physiol. 2021;12:712583. PubMed PMID: 34552503
Kumar S, Frid MG, Zhang H, Li M, Riddle S, Brown RD, Yadav SC, Roy MK, Dzieciatkowska ME, D'Alessandro A, Hansen KC, Stenmark KR. Complement-containing small extracellular vesicles from adventitial fibroblasts induce proinflammatory and metabolic reprogramming in macrophages. JCI Insight. 2021 Nov 8;6(21). PubMed PMID: 34499621
Stenmark KR, Frid MG, Gerasimovskaya E, Zhang H, McCarthy MK, Thurman JM, Morrison TE. Mechanisms of SARS-CoV-2-induced lung vascular disease: potential role of complement. Pulm Circ. 2021 Apr-Jun;11(2):20458940211015799. PubMed PMID: 34046161
Hu CJ, Poth JM, Zhang H, Flockton A, Laux A, Kumar S, McKeon B, Mouradian G, Li M, Riddle S, Pugliese SC, Brown RD, Wallace EM, Graham BB, Frid MG, Stenmark KR. Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension. Eur Respir J. 2019 Dec;54(6). PubMed PMID: 31515405
Zhang H, Laux A, Stenmark KR, Hu CJ. Mechanisms Contributing to the Dysregulation of miRNA-124 in Pulmonary Hypertension. Int J Mol Sci. 2021 Apr 8;22(8). PubMed PMID: 33917769
Li M, Riddle S, Kumar S, Poczobutt J, McKeon BA, Frid MG, Ostaff M, Reisz JA, Nemkov T, Fini MA, Laux A, Hu CJ, El Kasmi KC, D'Alessandro A, Brown RD, Zhang H, Stenmark KR. Microenvironmental Regulation of Macrophage Transcriptomic and Metabolomic Profiles in Pulmonary Hypertension. Front Immunol. 2021;12:640718. PubMed PMID: 33868271
Hui Zhang, Christine Vohwinkel, Aline Maddux, and Kurt R. Stenmark. Disease of Pulmonary Circulation. Pediatric Critical Care, 6th Edition. ISBN: 9780323672696. ELSEVIER 2021, pp 608-624.
Hui Zhang, R. Dale Brown, Jason Williams, Cassidy Delaney and Kurt R. Stenmark. Hypoxic remodeling of neonatal pulmonary artery and myocardium. Hypoxic Respiratory Failure in the Newborn, 1st Edition. ISBN 9780367493998. 2021.
Hui Zhang, Aya Laux, Kurt R. Stenmark, and Cheng-Jun Hu. Mechanisms Contributing to the Dysregulation of miRNA-124 in Pulmonary Hypertension. Am J Respir Crit Care Med 2021;201:A3664.
Min Li, Aya Laux, Hui Zhang, Cheng-Jun Hu, Kurt R. Stenmark. C-Terminal Binding Protein-1 Regulates Adventitial Fibroblast Metabolic and Mitochondrial Reprogramming in Pulmonary Hypertension Through Sirtuins. Am J Respir Crit Care Med 2021;201:A3635.
Cheng Jun Hu, Aya Laux, Liyi Wang, Hui Zhang ,Maria G Frid, Li Min, Suzette Riddle, Kurt R. Stenmark. Induction and maintenance of the activated phenotype of fibroblasts from hypoxia-induced pulmonary hypertensive calves depend on transcription factors activated by growth factors and cytokines, but not directly by hypoxia inducible factors. Am J Respir Crit Care Med 2021;201:A3633.
Hu CJ, Zhang H, Laux A, Pullamsetti SS, Stenmark KR. Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension. J Physiol. 2019 Feb;597(4):1103-1119. PubMed PMID: 29920674
Diseases of the Pulmonary Circulation
Hypoxic remodeling of neonatal pulmonary artery and myocardium
Campbell NV, Mickael C, Kumar S, Zhang H, Campbell IL, Gillen AE, Trentin CO, Diener K, Gao B, Kheyfets VO, Gu S, Kumar R, Phang T, Brown RD, Graham BB, Stenmark KR. Single-cell RNA sequencing and binary hierarchical clustering define lung interstitial macrophage heterogeneity in response to hypoxia. Am J Physiol Lung Cell Mol Physiol. 2022 Jul 1;323(1):L58-L68. PubMed PMID: 35608266
Combined inhibition of Histone Deacetylases and Bromodomain Proteins normalizes persistent activation of pulmonary hypertensive adventitial fibroblasts
ATAC-Seq Reveals That Genes Involved In The Persistently Activated Phenotype of PH Fibroblasts Exhibit Open Enhancers and Promoters That Are Enriched In Binding Sites For Several Transcription Factors
Epigenetic-targeted Therapies in Pulmonary Hypertension: Combined inhibition of Histone Deacetylases and Bromodomain Proteins Normalizes the Persistent Activation of Pulmonary Vascular Adventitial Fibroblasts in Vitro
SIRT3 Regulates Mitochondrial Function of Adventitial Fibroblasts in Pulmonary Hypertension
Chromatin Structure Alterations in Genes Involved in The Persistently Activated Phenotype of PH Vascular Cells
C-Terminal Binding Protein-1 Regulates Adventitial Fibroblast Metabolic and Mitochondrial Reprogramming in Pulmonary Hypertension Through Sirtuins
Fibroblast-secreted exosomal complement protein promotes macrophage polarization towards a pro-inflammatory phenotype
Plasma-Derived Small Extracellular Vesicles from Hypoxic Calves Drive Pro-Inflammatory and Metabolic Reprogramming in Macrophages
Hypoxia, Cytokines, and Growth Factors Exhibit Distinct and Synergistic Roles in Transforming Normal Pulmonary Fibroblasts intoPersistently Activated Fibroblasts
Plecitá-Hlavatá L, Brázdová A, Krivonosková M, Hu CJ, Phang T, Tauber J, Li M, Zhang H, Hoetzenecker K, Crnkovic S, Kwapiszewska G, Stenmark KR. Microenvironmental regulation of T-cells in pulmonary hypertension. Front Immunol. 2023;14:1223122. PubMed PMID: 37497214
Li M, Plecitá-Hlavatá L, Dobrinskikh E, McKeon BA, Gandjeva A, Riddle S, Laux A, Prasad RR, Kumar S, Tuder RM, Zhang H, Hu CJ, Stenmark KR. SIRT3 Is a Critical Regulator of Mitochondrial Function of Fibroblasts in Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2023 Nov;69(5):570-583. PubMed PMID: 37343939
Zhang H, Gerasimovskaya E, McCarthy MK, May NA, Prasad RR, Riddle S, McKeon BA, Kumar S, Li M, Hu CJ, Frid MG, Morrison TE, Stenmark KR. Local Complement Contributes to Pathogenic Activation of Lung Endothelial Cells in SARS-CoV-2 Infection. Am J Respir Cell Mol Biol. 2023 Aug;69(2):210-219. PubMed PMID: 37071849
Brown RD, Hunter KS, Li M, Frid MG, Harral J, Krafsur GM, Holt TN, Williams J, Zhang H, Riddle SR, Edwards MG, Kumar S, Hu CJ, Graham BB, Walker LA, Garry FB, Buttrick PM, Lahm T, Kheyfets VO, Hansen KC, Stenmark KR. Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model. Am J Physiol Heart Circ Physiol. 2023 Jun 1;324(6):H804-H820. PubMed PMID: 36961489
Hu CJ, Laux A, Gandjeva A, Wang L, Li M, Brown RD, Riddle S, Kheyfets VO, Tuder RM, Zhang H, Stenmark KR. The Effect of Hypoxia-inducible Factor Inhibition on the Phenotype of Fibroblasts in Human and Bovine Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2023 Jul;69(1):73-86. PubMed PMID: 36944195
Zhang H, D'Alessandro A, Li M, Reisz JA, Riddle S, Muralidhar A, Bull T, Zhao L, Gerasimovskaya E, Stenmark KR. Histone deacetylase inhibitors synergize with sildenafil to suppress purine metabolism and proliferation in pulmonary hypertension. Vascul Pharmacol. 2023 Apr;149:107157. PubMed PMID: 36849042