Research Topics
Genomes and Genes
| Kurt R StenmarkSummaryAffiliation: University of Colorado Health Sciences Center Country: USA Publications
Research Grants
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Detail Information
Publications
Sustained hypoxia leads to the emergence of cells with enhanced growth, migratory, and promitogenic potentials within the distal pulmonary artery wallMaria G Frid
Department of Pediatrics, University of Colorado Denver, Aurora, 80045, USA
Am J Physiol Lung Cell Mol Physiol 297:L1059-72. 2009..These data suggest that the cellular mechanisms of dPA remodeling include the emergence of cells with phenotypic and functional characteristics markedly distinct from those of resident dPA cells...
Role of the adventitia in pulmonary vascular remodelingKurt R Stenmark
Division of Pediatric Critical Care, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA
Physiology (Bethesda) 21:134-45. 2006..The purpose of this review is to present the current evidence demonstrating that the adventitial fibroblast acts as a key regulator of pulmonary vascular function and structure from the "outside-in."..- Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasiaKurt R Stenmark
Developmental Lung Biology Laboratory, Department of Pediatrics, University of Colorado Health Sciences Center and The Children s Hospital, Denver, Colorado 80262, USA
Annu Rev Physiol 67:623-61. 2005..We speculate that understanding basic mechanisms that regulate and determine vascular growth will lead to new clinical strategies to improve the long-term outcome of premature babies with BPD... - Hypoxia, leukocytes, and the pulmonary circulationKurt R Stenmark
Developmental Lung Biology Laboratory, Univ of Colorado Health Sciences Center, 4200 E 9th Ave, Box B131, Denver, CO 80262, USA
J Appl Physiol 98:715-21. 2005.... - Hypoxic activation of adventitial fibroblasts: role in vascular remodelingKurt R Stenmark
Developmental Lung Biology Research Laboratory, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Chest 122:326S-334S. 2002.... - Lung vascular development: breathing new life into an old problemKurt R Stenmark
Department of Pediatrics, Developmental Lung Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Am J Respir Cell Mol Biol 28:133-7. 2003 - Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanismsKurt R Stenmark
Department of Pediatrics, Developmental Lung Biology Laboratory, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA
Circ Res 99:675-91. 2006..This review provides perspectives on each of the aforementioned areas... - PI3K, Rho, and ROCK play a key role in hypoxia-induced ATP release and ATP-stimulated angiogenic responses in pulmonary artery vasa vasorum endothelial cellsHeather N Woodward
Department of Pediatrics, 12700 E 19th Ave, University of Colorado Denver, Research Complex 2, Box B131, Aurora, CO 80045, USA
Am J Physiol Lung Cell Mol Physiol 297:L954-64. 2009..Taken together, our findings provide novel evidence for the signaling mechanisms that link hypoxia-induced increases in extracellular ATP and vasa vasorum expansion... - Extracellular ATP is a pro-angiogenic factor for pulmonary artery vasa vasorum endothelial cellsEvgenia V Gerasimovskaya
Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, B131, 4200 East 9th Ave, Denver, CO 80262, USA
Angiogenesis 11:169-82. 2008..Collectively, our data support the idea that extracellular ATP participates in the expansion of the vasa vasorum that can be observed in hypoxic conditions... - Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineageMaria G Frid
Department of Pediatrics, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262, USA
Am J Pathol 168:659-69. 2006..We conclude that circulating mesenchymal precursors of a monocyte/macrophage lineage, including fibrocytes, are essential contributors to hypoxia-induced pulmonary vascular remodeling... - Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblastsMegan Short
Department of Pediatrics, Developmental Lung Biology Research Laboratories, University of Colorado Health Sciences Center, 4200 E. 9th Ave, Denver, CO 80262, USA
Am J Physiol Cell Physiol 286:C416-25. 2004.... - Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertensionAdil Anwar
Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Am J Physiol Lung Cell Mol Physiol 303:L1-L11. 2012..Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH... - Xanthine oxidase-derived ROS upregulate Egr-1 via ERK1/2 in PA smooth muscle cells; model to test impact of extracellular ROS in chronic hypoxiaTanya Hartney
Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, United States of America
PLoS ONE 6:e27531. 2011..We conclude that an oxidant/antioxidant imbalance arising from loss of EC-SOD in the PA with chronic hypoxia induces Egr-1 via activation of ERK1/2 and contributes to pulmonary vascular remodeling... 
Hypoxia exposure induces the emergence of fibroblasts lacking replication repressor signals of PKCzeta in the pulmonary artery adventitiaMita Das
Department of Pediatrics, B131, University of Colorado Denver, School of Medicine, 4200 E 9th Avenue, Denver, CO 80262, USA
Cardiovasc Res 78:440-8. 2008....- Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertensionMin Li
Division of Critical Care Medicine, Department of Pediatrics, University of Colorado at Denver, Aurora, CO 80045, USA
J Immunol 187:2711-22. 2011.... - Effects of pathological flow on pulmonary artery endothelial production of vasoactive mediators and growth factorsMin Li
Department of Pediatrics and CVP Research, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA
J Vasc Res 46:561-71. 2009..We therefore examined effects of pathologically low and high flow on endothelial production of factors capable of affecting pulmonary vascular tone and structure as well as on potential underlying mechanisms... - Extracellular ATP-induced proliferation of adventitial fibroblasts requires phosphoinositide 3-kinase, Akt, mammalian target of rapamycin, and p70 S6 kinase signaling pathwaysEvgenia V Gerasimovskaya
Developmental Lung Biology Laboratory, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 280:1838-48. 2005.... - Activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferationEvgenia V Gerasimovskaya
Developmental Lung Biology Laboratory, Univ of Colorado Health Sciences Center, 4200 E 9th Ave, Box B131, Denver, CO 80262, USA
J Appl Physiol 98:722-31. 2005.... - Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1Neil J Davie
Department of Pediatric Cardiology, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box C218, Denver, CO 80262, USA
Am J Pathol 168:1793-807. 2006.... - Lung extracellular superoxide dismutase overexpression lessens bleomycin-induced pulmonary hypertension and vascular remodelingZachary Van Rheen
Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA
Am J Respir Cell Mol Biol 44:500-8. 2011.... - Protein kinase Czeta attenuates hypoxia-induced proliferation of fibroblasts by regulating MAP kinase phosphatase-1 expressionMegan D Short
Developmental Lung Biology Research Laboratory, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Mol Biol Cell 17:1995-2008. 2006.... - Extracellular adenosine triphosphate: a potential regulator of vasa vasorum neovascularization in hypoxia-induced pulmonary vascular remodelingEvgenia V Gerasimovskaya
University of Colorado Health Sciences Center, Denver, CO 80262, USA
Chest 128:608S-610S. 2005 - Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cellsNeil J Davie
Developmental Lung Biology Group, UCHSC, 4200 East 9 th Ave, Rm 3419, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 286:L668-78. 2004..From these observations, we suggest that the vasa vasorum and circulating progenitor cells could be involved in vessel wall thickening in the setting of hypoxia-induced PH... - Egr-1 antisense oligonucleotides inhibit hypoxia-induced proliferation of pulmonary artery adventitial fibroblastsMark F Banks
Developmental Lung Biology Laboratory, Univ of Colorado Health Sciences Center, 4200 E 9th Ave, Box B131, Denver, CO 80262, USA
J Appl Physiol 98:732-8. 2005..We conclude that Egr-1 protein expression is very sensitive to upregulation by hypoxia in pulmonary artery adventitial fibroblasts and that it plays an important role in the autonomous growth phenotype induced by hypoxia in these cells... - Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calvesSteven R Lammers
Mechanical Engineering, University of Colorado, Boulder, Colorado, USA
Am J Physiol Heart Circ Physiol 295:H1451-9. 2008..These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue... - Circulating mononuclear cells with a dual, macrophage-fibroblast phenotype contribute robustly to hypoxia-induced pulmonary adventitial remodelingMaria G Frid
University of Colorado Health Sciences Center, Developmental Lung Biology Research Laboratory, Denver, CO 80262, USA
Chest 128:583S-584S. 2005 - Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodelingJoseph T Crossno
Pulmonary and Critical Care Services, Veterans Affairs Medical Center, Denver, USA
Am J Physiol Lung Cell Mol Physiol 292:L885-97. 2007..However, this agent fails to block the development of PH, apparently because of its inability to repress sustained Rho kinase-mediated arterial vasoconstriction... - Unique, highly proliferative growth phenotype expressed by embryonic and neointimal smooth muscle cells is driven by constitutive Akt, mTOR, and p70S6K signaling and is actively repressed by PTENPeter M Mourani
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colo 80262, USA
Circulation 109:1299-306. 2004..The aim of the present study was to evaluate the functional role of S6 ribosomal protein (S6RP) and upstream positive and negative regulators in the control of SMC serum-independent growth... - Bovine distal pulmonary arterial media is composed of a uniform population of well-differentiated smooth muscle cells with low proliferative capabilitiesLeopold Stiebellehner
Developmental Lung Biology Research, Univ. of Colorado Health Sciences Center, 4200 E. 9th Ave, Box B131, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 285:L819-28. 2003..We thus speculate that distinct SMC phenotypes present in distal vs. proximal PA may confer different response mechanisms during remodeling in conditions such as hypertension... - Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factorEvgenia V Gerasimovskaya
Developmental Lung Biology Research Laboratory, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 277:44638-50. 2002..We conclude that hypoxia induces ATP release from endothelial cells and fibroblasts and that the activation of P2 purinoceptors is involved in the regulation of DNA synthesis by fibroblasts under hypoxic conditions... - Validation of a pressure diameter method for determining modulus and strain of collagen engagement for long branches of bovine pulmonary arteriesMark Reusser
Department of Bioengineering, University of Colorado, Denver, CO 80045, USA
J Biomech Eng 134:054501. 2012..The method allowed faster testing of tissues of multiple diameters, while removing the effect of end conditions. The PD method will be of further utility in continued study of tissue mechanics in pulmonary hypertension studies... - Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calvesLian Tian
Department of Mechanical Engineering, University of Colorado, Boulder, Colorado, USA
Am J Physiol Heart Circ Physiol 301:H1810-8. 2011..We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics... - Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodelingEva Nozik-Grayck
Department of Pediatrics, Univ of Colorado, Denver, 4200 E 9th Ave, B131, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 295:L422-30. 2008..These data provide the first evidence that EC-SOD activity is disrupted in chronic hypoxia, and increased EC-SOD activity can attenuate chronic hypoxic PH by limiting the hypoxic upregulation of redox-sensitive genes... - Embryonic growth-associated protein is one subunit of a novel N-terminal acetyltransferase complex essential for embryonic vascular developmentJanet M Wenzlau
Department of Renal Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Circ Res 98:846-55. 2006..These data suggest the EGAP NAT complex is an essential regulatory enzyme controlling the function of a subset of proteins required for embryonic growth control and vessel development... - Sustained lung activity of a novel chimeric protein, SOD2/3, after intratracheal administrationMargaret B Clarke
Pediatric Critical Care, Department of Pediatrics, University of Colorado at Denver, Aurora, CO 80045, USA
Free Radic Biol Med 49:2032-9. 2010..Further testing in models of chronic lung or pulmonary vascular diseases mediated by excess superoxide should consider the longer tissue half-life of SOD2/3 as well as its potential systemic vascular effects... - Hypoxia-induced alterations in protein kinase C zeta signaling result in augmented fibroblast proliferationMegan Short
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Chest 128:582S. 2005 - Hypoxia protects human lung microvascular endothelial and epithelial-like cells against oxygen toxicity: role of phosphatidylinositol 3-kinaseShama Ahmad
Department of Pediatrics, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado, USA
Am J Respir Cell Mol Biol 28:179-87. 2003..These results indicate that hypoxia-induced activation of PI3-K is an important event in the acquisition of resistance against subsequent hyperoxic toxicity... - P2Y1 and P2Y13 purinergic receptors mediate Ca2+ signaling and proliferative responses in pulmonary artery vasa vasorum endothelial cellsTaras Lyubchenko
Dept of Pediatrics, University of Colorado Denver, Research 2, Box B131, Aurora, CO 80045, USA
Am J Physiol Cell Physiol 300:C266-75. 2011.... - Eph-A2 promotes permeability and inflammatory responses to bleomycin-induced lung injuryTodd C Carpenter
Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora, 80045, USA
Am J Respir Cell Mol Biol 46:40-7. 2012..This study demonstrates that the expression of EphA2 increases in the injured lung, and not only contributes to changes in permeability, but also plays a previously unrecognized role in promoting inflammatory responses... - Yin and Yang of an endothelial cell: from normal to the extreme in growth, secretion, and transdifferentiation capabilitiesMaria G Frid
Pediatric Critical Care, University of Colorado Health Sciences Center, Box B131, 4200 E 9th Avenue, Denver, CO 80262, USA
Paediatr Respir Rev 5:S253-7. 2004 - Plasma proteomics of differential outcome to long-term therapy in children with idiopathic pulmonary arterial hypertensionMichael E Yeager
Department of Pediatric Critical Care, University of Colorado Denver, Denver, CO 80045, USA
Proteomics Clin Appl 6:257-67. 2012..The prognosis for children with IPAH unresponsive to therapy is poor. We investigated the plasma proteome for a molecular basis of good versus poor outcome to long-term vasodilator therapy... - Induction of SM-alpha-actin expression by mechanical strain in adult vascular smooth muscle cells is mediated through activation of JNK and p38 MAP kinaseJenny Tock
Department of Pediatrics, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Box C-281, 4200 E. Ninth Ave, Denver, CO 80262, USA
Biochem Biophys Res Commun 301:1116-21. 2003..These studies indicate that in adult VSMC, mechanical strain leads to increased expression of smooth muscle markers, resulting in a more contractile phenotype... - Distensibility of the normal human lung circulation during exerciseJohn T Reeves
University of Colorado Health Sciences Center, 4200 E. 9th Ave, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 288:L419-25. 2005..We propose that the estimation of pulmonary vascular distensibility in humans may be a useful descriptor of pulmonary hemodynamics... - Activation of the unfolded protein response is associated with pulmonary hypertensionMichael E Yeager
Department of Pediatrics, Division of Pulmonary and Critical Care Medicine, University of Colorado Denver, Aurora, Colorado, USA
Pulm Circ 2:229-40. 2012..As such, understanding the functional contributions of the UPR in the setting of PH may have important therapeutic implications... - Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic changeKurt R Stenmark
Department of Pediatric Gastroenterology, Pediatric Critical Care Developmental Lung Biology Laboratory, University of Colorado, Aurora, Colorado, USA
Pulm Circ 2:3-14. 2012..At present, therapies specifically targeting abnormalities of histone deacytelase (HDAC) activity in fibroblast-like cells appear to hold promise... - Emerging therapies for the treatment of pulmonary hypertensionKurt R Stenmark
Developmental Lung Biology Laboratory, University of Colorado Denver, Aurora, CO, USA
Pediatr Crit Care Med 11:S85-90. 2010.... - Role of reactive oxygen species in chronic hypoxia-induced pulmonary hypertension and vascular remodelingEva Nozik Grayck
Department of Pediatrics and Developmental Lung Biology Laboratory, University of Colorado at Denver and Health Science Center, Denver, Colorado, USA
Adv Exp Med Biol 618:101-12. 2007.... - Endothelin-mediated increases in lung VEGF content promote vascular leak in young rats exposed to viral infection and hypoxiaTodd C Carpenter
Developmental Lung Biology Laboratory, Box B 131, University of Colorado School of Medicine, 4200 E 9th Avenue, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 289:L1075-82. 2005..These findings suggest that ET-driven increases in lung VEGF content can contribute to the formation of pulmonary edema... - Connective tissue growth factor expression is increased in biliary epithelial cells in biliary atresiaMichael R Narkewicz
Department of Pediatrics, The Pediatric Liver Center, The Children s Hospital, University of Colorado School of Medicine, Denver, CO 80218, USA
J Pediatr Surg 40:1721-5. 2005..The objective of this study was to evaluate hepatic CTGF messenger RNA (mRNA) expression and its relationship to hepatic histology in children with BA... - Complementary effects of extracellular nucleotides and platelet-derived extracts on angiogenesis of vasa vasorum endothelial cells in vitro and subcutaneous Matrigel plugs in vivoMark Roedersheimer
Department of Pediatrics, University of Colorado Denver, 12700 East 19th Ave, Aurora, CO 80045, USA
Vasc Cell 3:4. 2011..abstract:.. - Predisposition of infants with chronic lung disease to respiratory syncytial virus-induced respiratory failure: a vascular hypothesisTodd C Carpenter
Developmental Lung Biology Laboratory, University of Colorado Health Sciences Center, Denver, 80602, USA
Pediatr Infect Dis J 23:S33-40. 2004..CONCLUSIONS: Novel therapies for managing RSV-induced respiratory failure in the infant with CLD/BPD must consider factors responsible for the substantial pulmonary vascular component of this illness... - Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expressionTodd C Carpenter
Department of Pediatrics and Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA
Am J Physiol Lung Cell Mol Physiol 284:L77-83. 2003.... - Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation: in vitro analysisMaria G Frid
Developmental Lung Biology Research Laboratory, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
Circ Res 90:1189-96. 2002.... - Circulating myeloid-derived suppressor cells are increased and activated in pulmonary hypertensionMichael E Yeager
Department of Pediatrics, Division of Pulmonary and Critical Care Medicine, University of Colorado, Denver, Aurora, CO 80045, USA
Chest 141:944-52. 2012..Immature myeloid cells are found in the lungs of humans and animals with PH, and we hypothesized that they would be increased in the blood of patients with PH compared with control subjects... - Progenitor cells in pulmonary vascular remodelingMichael E Yeager
Department of Pediatrics and Critical Care, University of Colorado at Denver and Health Sciences Center, Colorado, USA
Pulm Circ 1:3-16. 2011.... - Perlecan up-regulation of FRNK suppresses smooth muscle cell proliferation via inhibition of FAK signalingHeather A Walker
Department of Pediatrics, Renal Division, University of Colorado Health Sciences Center, Denver 80262, USA
Mol Biol Cell 14:1941-52. 2003..FRNK, in turn, may control SMC growth by downregulating FAK-dependent signaling events... - Cellular and molecular pathobiology of pulmonary arterial hypertensionMarc Humbert
Service de Pneumologie et Reanimation Respiratoire, Centre des Maladies Vasculaires Pulmonaires, UPRES EA2705, Hopital Antoine Beclere, Universite Paris Sud, Clamart, France
J Am Coll Cardiol 43:13S-24S. 2004..Disordered proteolysis of the extracellular matrix is also evident in PAH. Future studies are required to find which if any of these abnormalities initiates PAH and which ones are best targeted to cure the disease... - Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertensionEnrique Arciniegas
Laboratorio de Microscopía Electrónica, Servicio Autónomo Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
Am J Physiol Lung Cell Mol Physiol 293:L1-8. 2007..Thus insights into the mechanisms controlling endothelial-mesenchymal transition are relevant to vascular remodeling and are important as we consider new therapies aimed at reversing pulmonary vascular remodeling... - Angiogenic therapy for bronchopulmonary dysplasia: rationale and promiseKurt R Stenmark
Circulation 112:2383-5. 2005 - Vascular remodeling versus vasoconstriction in chronic hypoxic pulmonary hypertension: a time for reappraisal?Kurt R Stenmark
Circ Res 97:95-8. 2005
Research Grants
- Lung Vascular Disease in Infants and Children: Mechanisms and TreatmentKurt Stenmark; Fiscal Year: 2007..End of Abstract) ..
- RESPIRATION AND CIRCULATION DURING HYPOXIAKurt Stenmark; Fiscal Year: 2007..The program director, with the advice and consent of the senior program faculty is responsible for the administration and coordination of the program. ..