Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension

JCI Insight

Volumn 1, Issue 8, 2016, Pages

  Liu, Fei ^a   Haeger, Christina Mallarino ^b   Dieffenbach, Paul B ^b   Sicard, Delphine ^c   Chrobak, Izabela ^d   Coronata, Anna Maria F ^b   Suárez Velandia, Margarita M ^b   Vitali, Sally ^e   Colas, Romain A ^b   Norris, Paul C ^b   Marinković, Aleksandar ^a   Liu, Xiaoli ^b   Ma, Jun ^b   Rose, Chase D ^e   Lee, Seon Jin ^b,f   Comhair, Suzy A A ^g   Erzurum, Serpil C ^g   McDonald, Jacob D ^d   Serhan, Charles N ^b   Walsh, Stephen R ^b   Tschumperlin, Daniel J ^a,c   Fredenburgh, Laura E ^b   more..

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c MAYO GRADUATE SCHOOL   (United States)

^d LOVELACE RESPIRATORY RESEARCH INSTITUTE   (United States)

^e BOSTON CHILDREN S HOSPITAL   (United States)

^f Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

^g LERNER RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85065414168     PISSN: None     EISSN: 23793708     Source Type: Journal    
DOI: 10.1172/jci.insight.86987     Document Type: Article

References (79)

1. Fredenburgh LE, Ma J, Perrella MA. Cyclooxygenase-2 inhibition and hypoxia-induced pulmonary hypertension: effects on pulmonary vascular remodeling and contractility. Trends Cardiovasc Med. 2009;19(2):31–37.
2. Kaess BM, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308(9):875–881.
3. Laurent S, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37(5):1236–1241.
4. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99(18):2434–2439.
5. Gan CT, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest. 2007;132(6):1906–1912.
6. Rodes-Cabau J, et al. Intravascular ultrasound of the elastic pulmonary arteries: a new approach for the evaluation of primary pulmonary hypertension. Heart. 2003;89(3):311–315.
7. Mahapatra S, Nishimura RA, Sorajja P, Cha S, McGoon MD. Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. J Am Coll Cardiol. 2006;47(4):799–803.
8. Hunter KS, et al. Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension. Am Heart J. 2008;155(1):166–174.
9. Wang Z, Chesler NC. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ. 2011;1(2):212–223.
10. Stevens GR, Garcia-Alvarez A, Sahni S, Garcia MJ, Fuster V, Sanz J. RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness. JACC Cardiovasc Imaging. 2012;5(4):378–387.
11. Kang KW, et al. Cardiac magnetic resonance imaging-derived pulmonary artery distensibility index correlates with pulmonary artery stiffness and predicts functional capacity in patients with pulmonary arterial hypertension. Circ J. 2011;75(9):2244–2251.
12. Klein EA, et al. Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening. Curr Biol. 2009;19(18):1511–1518.
13. Liu F, et al. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol. 2015;308(4):L344–L357.
14. Liu F, et al. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression. J Cell Biol. 2010;190(4):693–706.
15. Ooi CY, Wang Z, Tabima DM, Eickhoff JC, Chesler NC. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2010;299(6):H1823–H1831.
16. Kobs RW, Muvarak NE, Eickhoff JC, Chesler NC. Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension. Am J Physiol Heart Circ Physiol. 2005;288(3):H1209–H1217.
17. Tabima DM, Chesler NC. The effects of vasoactivity and hypoxic pulmonary hypertension on extralobar pulmonary artery bio-mechanics. J Biomech. 2010;43(10):1864–1869.
18. Tuchscherer HA, Vanderpool RR, Chesler NC. Pulmonary vascular remodeling in isolated mouse lungs: effects on pulsatile pressure-flow relationships. J Biomech. 2007;40(5):993–1001.
19. Wang Z, Chesler NC. Role of collagen content and cross-linking in large pulmonary arterial stiffening after chronic hypoxia. Biomech Model Mechanobiol. 2011;11(1–2):279–289.
20. Drexler ES, et al. Stiffening of the extrapulmonary arteries from rats in chronic hypoxic pulmonary hypertension. J Res Natl Stand Technol. 2008;113(4):239–249.
21. Hunter KS, et al. In vivo measurement of proximal pulmonary artery elastic modulus in the neonatal calf model of pulmonary hypertension: development and ex vivo validation. J Appl Physiol. 2010;108(4):968–975.
22. Lammers SR, et al. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves. Am J Physiol Heart Circ Physiol. 2008;295(4):H1451–H1459.
23. Nave AH, et al. Lysyl oxidases play a causal role in vascular remodeling in clinical and experimental pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol. 2014;34(7):1446–1458.
24. Schafer M, et al. Pulmonary arterial stiffness: Toward a new paradigm in pulmonary arterial hypertension pathophysiology and assessment. Curr Hypertens Rep. 2016;18(1):4.
25. Tschumperlin DJ. Matrix, mesenchyme, and mechanotransduction. Ann Am Thorac Soc. 2015;12(suppl 1):S24–S29.
26. Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310(5751):1139–1143.
27. Mammoto T, Ingber DE. Mechanical control of tissue and organ development. Development. 2010;137(9):1407–1420.
28. Pelham RJ Jr, Wang Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci USA. 1997;94(25):13661–13665.
29. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–689.
30. Ivanovska IL, Shin JW, Swift J, Discher DE. Stem cell mechanobiology: diverse lessons from bone marrow. Trends Cell Biol. 2015;25(9):523–532.
31. Shin JW, et al. Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells. Cell Stem Cell. 2014;14(1):81–93.
32. Caiazzo M, Okawa Y, Ranga A, Piersigilli A, Tabata Y, Lutolf MP. Defined three-dimensional microenvironments boost induction of pluripotency. Nat Mater. 2016;15(3):344–352.
33. Paszek MJ, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell. 2005;8(3):241–254.
34. Taubenberger AV, et al. 3D extracellular matrix interactions modulate tumour cell growth, invasion angiogenesis in engineered tumour microenvironments. Acta Biomater. 2016;36:73–85.
35. Peyton SR, Putnam AJ. Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion. J Cell Physiol. 2005;204(1):198–209.
36. Engler A, Bacakova L, Newman C, Hategan A, Griffin M, Discher D. Substrate compliance versus ligand density in cell on gel responses. Biophys J. 2004;86(1 pt 1):617–628.
37. Shkumatov A, et al. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2015;308(11):L1125–L1135.
38. Liu F, Tschumperlin DJ. Micro-mechanical characterization of lung tissue using atomic force microscopy. J Vis Exp. 2011;(54):2911.
39. Fredenburgh LE, et al. Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation. 2008;117(16):2114–2122.
40. Tuder RM, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159(6):1925–1932.
41. Christman BW, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327(2):70–75.
42. Falcetti E, et al. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010;182(9):1161–1170.
43. Abe K, et al. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation. 2010;121(25):2747–2754.
44. Taraseviciene-Stewart L, et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J. 2001;15(2):427–438.
45. Mih JD, Sharif AS, Liu F, Marinkovic A, Symer MM, Tschumperlin DJ. A multiwell platform for studying stiffness-dependent cell biology. PLoS One. 2011;6(5):e19929.
46. Butler JP, Tolic-Norrelykke IM, Fabry B, Fredberg JJ. Traction fields, moments, and strain energy that cells exert on their surroundings. Am J Physiol Cell Physiol. 2002;282(3):C595–C605.
47. Marinkovic A, Mih JD, Park JA, Liu F, Tschumperlin DJ. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-beta responsiveness. Am J Physiol Lung Cell Mol Physiol. 2012;303(3):L169–L180.
48. Lau EM, Iyer N, Ilsar R, Bailey BP, Adams MR, Celermajer DS. Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo study with intravascular ultrasound. PLoS One. 2012;7(3):e33331.
49. Sanz J, et al. Evaluation of pulmonary artery stiffness in pulmonary hypertension with cardiac magnetic resonance. JACC Cardiovasc Imaging. 2009;2(3):286–295.
50. Mahapatra S, Nishimura RA, Oh JK, McGoon MD. The prognostic value of pulmonary vascular capacitance determined by Doppler echocardiography in patients with pulmonary arterial hypertension. J Am Soc Echocardiogr. 2006;19(8):1045–1050.
51. Weinberg CE, et al. Extraction of pulmonary vascular compliance, pulmonary vascular resistance, and right ventricular work from single-pressure and Doppler flow measurements in children with pulmonary hypertension: a new method for evaluating reactivity: in vitro and clinical studies. Circulation. 2004;110(17):2609–2617.
52. Kobs RW, Chesler NC. The mechanobiology of pulmonary vascular remodeling in the congenital absence of eNOS. Biomech Model Mechanobiol. 2006;5(4):217–225.
53. Tan W, Madhavan K, Hunter KS, Park D, Stenmark KR. Vascular stiffening in pulmonary hypertension: cause or consequence? (2013 Grover Conference series). Pulm Circ. 2014;4(4):560–580.
54. Benyahia C, et al. Ex vivo relaxations of pulmonary arteries induced by prostacyclin mimetics are highly dependent of the precontractile agents. Prostaglandins Other Lipid Mediat. 2015;121(pt A):46–52.
55. Clapp LH, Gurung R. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: Role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 2015;120:56–71.
56. Orie NN, Ledwozyw A, Williams DJ, Whittle BJ, Clapp LH. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins. Prostaglandins Other Lipid Mediat. 2013;106:1–7.
57. Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012;84(1):68–75.
58. Lang IM, Gaine SP. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015;24(138):630–641.
59. McLaughlin VV, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573–1619.
60. Farber HW, Miller DP, Meltzer LA, McGoon MD. Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL Registry. J Heart Lung Transplant. 2013;32(11):1114–1122.
61. Delcroix M, Spaas K, Quarck R. Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy. Eur Respir Rev. 2009;18(114):253–259.
62. Vachiery JL. Prostacyclins in pulmonary arterial hypertension: the need for earlier therapy. Adv Ther. 2011;28(4):251–269.
63. Jing ZC, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013;127(5):624–633.
64. Simonneau G, et al. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012;40(4):874–880.
65. Tschumperlin DJ, Boudreault F, Liu F. Recent advances and new opportunities in lung mechanobiology. J Biomech. 2010;43(1):99–107.
66. Huynh J, et al. Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration. Sci Transl Med. 2011;3(112):112ra122.
67. –/– mice quantified by atomic force, immunofluorescence, and light microscopy. J Vasc Res. 2011;48(6):495–504.
68. Liu SL, et al. Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening. Sci Rep. 2015;5:17189.
69. Lalich JJ, Merkow L. Pulmonary arteritis produced in rat by feeding Crotalaria spectabilis. Lab Invest. 1961;10:744–750.
70. Fredenburgh LE, et al. Absence of heme oxygenase-1 expression in the lung parenchyma exacerbates endotoxin-induced acute lung injury and decreases surfactant protein-B levels. Cell Mol Biol. 2005;51(5):513–520.
71. Fredenburgh LE, et al. Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during poly-microbial sepsis. J Immunol. 2011;187(10):5255–5267.
72. Samuel MS, et al. Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell. 2011;19(6):776–791.
73. Thundat T, Warmack RJ, Chen GY, Allison DP. Thermal and ambient-induced deflections of scanning force microscope cantilevers. Appl Phys Lett. 1994;64:2894–2896.
74. Dimitriadis EK, Horkay F, Maresca J, Kachar B, Chadwick RS. Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys J. 2002;82(5):2798–2810.
75. Hertz H. Über die Berührung fester elastischer Körper (On the contact of elastic solids). J Reine Angew Mathematik. 1881;92:156–171.
76. Butler JP, Nakamura M, Sasaki H, Sasaki T, Takishima T. Poissons’ ratio of lung parenchyma and parenchymal interaction with bronchi. Jpn J Physiol. 1986;36(1):91–106.
77. Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem. 2006;54(4):385–395.
78. Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol. 2014;307(1):C39–C54.
79. Comhair SA, Xu W, Mavrakis L, Aldred MA, Asosingh K, Erzurum SC. Human primary lung endothelial cells in culture. Am J Respir Cell Mol Biol. 2012;46(6):723–730.