Pericytes, microvasular dysfunction, and chronic rejection

Transplantation

Volumn 99, Issue 4, 2015, Pages 658-667

  Kloc, Malgorzata ^a   Kubiak, Jacek Z ^b   Li, Xian C ^a   Ghobrial, Rafik M ^a  

^a HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^b UNIVERSITÉ DE RENNES 1   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS; BLOOD VESSEL PERMEABILITY; CELL FUNCTION; CHRONIC GRAFT REJECTION; DRUG TARGETING; ENDOTHELIUM CELL; FIBROSIS; HUMAN; INFLAMMATION; MICROANGIOPATHY; MICROVASCULATURE; NONHUMAN; ORGAN TRANSPLANTATION; PERICYTE; PRIORITY JOURNAL; REVIEW; ADVERSE EFFECTS; ANIMAL; CELL COMMUNICATION; CELL TRANSDIFFERENTIATION; CHRONIC DISEASE; GRAFT REJECTION; METABOLISM; MICROCIRCULATION; PATHOLOGY; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; TREATMENT OUTCOME;

ANGIOGENIC PROTEIN; AUTACOID;

ANGIOGENIC PROTEINS; ANIMALS; CELL COMMUNICATION; CELL TRANSDIFFERENTIATION; CHRONIC DISEASE; ENDOTHELIAL CELLS; FIBROSIS; GRAFT REJECTION; HUMANS; INFLAMMATION MEDIATORS; MICROCIRCULATION; MICROVESSELS; MYOCYTES, SMOOTH MUSCLE; ORGAN TRANSPLANTATION; PERICYTES; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84930158029     PISSN: 00411337     EISSN: None     Source Type: Journal    
DOI: 10.1097/TP.0000000000000648     Document Type: Review

References (129)

1. Ozdemir BH, Demirhan B, Ozdemir FN, Dalgic A, Haberal M. The role of microvascular injury on steroid and OKT3 response in renal allograft rejection. Transplantation. 2004;78:734-740.
2. Babu AN, Murakawa T, Thurman JM, et al. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. J Clin Invest. 2007;117:3774-3785.
3. Biedermann BC, Sahner S, Gregor M, et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet. 2002;359:2078-2083.
4. Luckraz H, Goddard M, McNeil K, et al. Microvascular changes in small airways predispose to obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant. 2004;23:527-531.
5. Luckraz H, Goddard M, McNeil K, Atkinson C, Sharples LD, Wallwork J. Is obliterative bronchiolitis in lung transplantation associated with microvascular damage to small airways? Ann Thorac Surg. 2006;82: 1212-1218.
6. Khan MA, Nicolls MR. Complement-mediated microvascular injury leads to chronic rejection. Adv Exp Med Biol. 2013;735:233-246.
7. Jiang X, Khan MA, Tian W, et al. Adenovirus-mediated HIF-1? gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. J Clin Invest. 2011;121:2336-2349.
8. Eberth CJ. Handbuch der Lehre von der Gewegen des Menschen und der Tiere. 1871, Vol 1 (Leipzig).
9. Rouget C. Memoire sur le developpement, la structures et les proprietes des capillaires sanguins et lymphatiques. Arch Physiol Norm Pathol. 1873;5:603-633.
10. Zimmermann KW. Der feinere bau der blutcapillares. Z Anat Entwicklungsgesch. 1923;68:3-109.
11. Armulik A, Abramsson A, Betsholtz C. Endothelial/Pericyte Interactions. Circ Res. 2005;97:512-523.
12. Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21:193-215.
13. Kafalides NA, Borel JP. Basement Membranes: Cell and Molecular Biology. San Diego, CA: Elsevier Academic Press, 2005.
14. Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 2005;7:452-464.
15. Mandarino LJ, Sundarraj N, Finlayson J, Hassell HR. Regulation of fibronectin and laminin synthesis by retinal capillary endothelial cells and pericytes in vitro. Exp Eye Res. 1993;57:609-621.
16. Rucker HK, Wynder HJ, Thomas WE. Cellular mechanisms of CNS pericytes. Brain Res Bull. 2000;51:363-369.
17. Dore-Duffy P, Cleary K. Morphology and properties of pericytes. The blood-brain and other barriers. Methods Mol Biol. 2011;686:49.
18. Sims DE. The pericyte-a review. Tissue Cell. 1986;18:153-174.
19. Anastasia A, Deinhardt K, Wang S, et al. Trkb signaling in pericytes is required for cardiac microvessel stabilization. PLoS One. 2014;9:e87406.
20. LindblomP, Gerhardt H, Liebner S, et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev. 2003;17:1835-1840.
21. Ricard N, Tu L, Le Hiress M, et al. Increased pericyte coverage mediated by endothelial-derived fibroblast growth factor-2 and interleukin-6 is a source of smooth muscle-like cells in pulmonary hypertension. Circulation. 2014;129:1586-1597.
22. Stratman AN, Schwindt AE, Malotte KM, Davis GE. Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. Blood. 2010;116:4720-4730.
23. Kutcher ME, Herman IM. The pericyte: cellular regulator ofmicrovascular blood flow. Microvasc Res. 2009;77:235-246.
24. Papetti M, Shujath J, Riley KN, Herman IM. FGF-2 antagonizes the TGF-beta1-mediated induction of pericyte alpha-smooth muscle actin expression: a role for myf-5 and Smad-mediated signaling pathways. Invest Ophthalmol Vis Sci. 2003;44:4994-5005.
25. Pieper C, Marek JJ, Unterberg M, Schwerdtle T, Galla HJ. Brain capillary pericytes contribute to the immune defense in response to cytokines or in vitro. Brain Res. 2014;1550:1-8.
26. Stark K, Eckart A, Haidari S, et al. Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and 'instruct' them with pattern-recognition and motility programs. Nat Immunol. 2013;14:41-51.
27. Nehls V, Drenckhahn D. Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol. 1991;113:147-154.
28. Hughes S, Chan-Ling T. Characterization of smooth muscle cell and pericyte differentiation in the rat retina in vivo. Invest Ophthalmol Vis Sci. 2004;45:2795-2806.
29. Walter JJ, Sane DC. The role of smooth muscle cells and pericytes in angiogenesis. Chapter 3 in Angiogenesis Inhibitors and Stimulators: Potential Therapeutic Implications. Ed. Shaker A. Mousa. ©2000 Eurekah.com.
30. NakanoM, Atobe Y, Goris RC, et al. Ultrastructure of the capillary pericytes and the expression of smooth muscle alpha-actin and desmin in the snake infrared sensory organs. Anat Rec. 2000;260:299-307.
31. Skalli O, Pelte MF, Peclet MC, et al. Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem. 1989;37:315-321.
32. Nees S, Weiss DR, Senftl A, et al. Isolation, bulk cultivation, and characterization of coronary microvascular pericytes: the second most frequent myocardial cell type in vitro. Am J Physiol Heart Circ Physiol. 2012;302:H69-H84.
33. Liu G, Meng C, Pan M, et al. Isolation, purification, and cultivation of primary retinal microvascular pericytes: a novel model using rats. Microcirculation. 2014.
34. Birbrair A, Zhang T, Wang Z-M, et al. Skeletal muscle pericyte subtypes differ in their differentiation potential. Stem Cell Res. 2013;10:67-84.
35. Ando H, Kubin T, Schaper W, Schaper J. Cardiac microvascular endothelial cells express ?-smooth muscle actin and show low NOS III activity. Am J Physiol. 1999;276:H1755-H1768.
36. Ludin A, Itkin T, Gur-Cohen S, et al. Monocytes-macrophages that express ?-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow. Nat Immunol. 2012;13:1072-1082.
37. Nagamoto T, Eguchi G, Beebe DC. Alpha-smooth muscle actin expression in cultured lens epithelial cells. Invest Ophthalmol Vis Sci. 2000;41:1122-1129.
38. Kiss B, Kellermayer MS. Stretching desmin filaments with receding meniscus reveals large axial tensile strength. J Struct Biol. 2014.
39. Li Z, Mericskay M, AgbulutO, et al. Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle. J Cell Biol. 1997;139:129-144.
40. Trotter J, Karram K, Nishiyama N. NG2 cells: properties, progeny and origin. Brain Res Rev. 2010;63:72-82.
41. Eisenmann KM, McCarthy JB, Simpson MA, et al.Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol. 1999;1:507-513.
42. Ozerdem U, Monosov E, StallcupWB. NG2 proteoglycan expression by pericytes in pathological microvasculature. Microvasc Res. 2002;63: 129-134.
43. Ozerdem U, Stallcup WB. Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis. 2004;7:269-276.
44. Binamé F. Transduction of extracellular cues into cell polarity: the role of the transmembrane proteoglycan NG2. Mol Neurobiol. 2014.
45. Huang W, Zhao N, Bai X, et al. Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development. Glia. 2014;62:896-913.
46. Li Y, Wang J, Rizvi SM, et al. In vitro targeting of NG2 antigen by 213Bi-9.2.27 alpha-immunoconjugate induces cytotoxicity in human uveal melanoma cells. Invest Ophthalmol Vis Sci. 2005;46:4365-4371.
47. Murfee WL, Skalak TC, Peirce SM. Differential arterial/venous expression of NG2 proteoglycan in perivascular cells along microvessels: identifying a venule-specific phenotype. Microcirculation. 2005;12:151-160.
48. Proebsti D, Voisin M-B, Woodfin A, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. 2012;209:1219-1234.
49. Alon R, Nourshargh S. Learning in motion: pericytes instruct migrating innate leukocytes. Nat Immunol. 2013;14:14-15.
50. Rangel R, Sun Y, Guzman-Rojas L, et al. Impaired angiogenesis in aminopeptidase N-null mice. Proc Natl Acad Sci USA. 2007;104: 4588-4593.
51. Gerlach JC, Over P, Turner ME, et al. Perivascular mesenchymal progenitors in human fetal and adult liver. Stem Cells Dev. 2012;21: 3258-3269.
52. Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9: 653-660.
53. Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 1999;126:3047-3055.
54. Lugassy C, Wadehra M, Li X, et al. Pilot study on "pericytic mimicry" and potential embryonic/stem cell properties of angiotropic melanoma cells interacting with the abluminal vascular surface. Cancer Microenviron. 2013;6:19-29.
55. Montiel-Eulefi E, Nery AA, Rodrigues LC, Sánchez R, Romero F, Ulrich H. Neural differentiation of rat aorta pericyte cells. Cytometry A. 2012;81:65-71.
56. Tsang WP, Shu Y, Kwok PL, et al. CD146+ human umbilical cord perivascular cells maintain stemness under hypoxia and as a cell source for skeletal regeneration. PLoS One. 2013;8:e76153.
57. Collett G, Wood A, Alexander MY, et al. Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circ Res. 2003;92: 1123-1129.
58. Dellavalle A, Sampaolesi M, Tonlorenzi R, et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol. 2007;9:255-267.
59. Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation. 2004;110:2226-2232.
60. Lin SL, Kisseleva T, Brenner DA, Duffield JS. Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol. 2008;173:1617-1627.
61. Göritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisén J. A pericyte origin of spinal cord scar tissue. Science. 2011;333:238-242.
62. Ho YY, Lagares D, Tager AM, Kapoor M. Fibrosis-a lethal component of systemic sclerosis. In: Nat Rev Rheumatol. 2014.
63. Wight TN, Potter-Perigo S. The extracellular matrix: an active or passive player in fibrosis? Am J Physiol Gastrointest Liver Physiol. 2011;301: G950-G955.
64. Hutchison N, Fligny C, Duffield JS. Resident mesenchymal cells and fibrosis. Biochim Biophys Acta. 1832;2012:962-971.
65. Powell DW, Pinchuk IV, Saada JI, Chen X, Mifflin RC. Mesenchymal cells of the intestinal lamina propria. Annu Rev Physiol. 2011;73:213-237.
66. Humphreys BD, Lin S-L, Kobayashi A, et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol. 2012;176:85-97.
67. Fabris L, Strazzabosco M. Epithelial-mesenchymal interactions in biliary diseases. Semin Liver Dis. 2011;31:11-32.
68. Schrimpf C, Duffield JS. Mechanisms of fibrosis: the role of the pericyte. Curr Opin Nephrol Hypertens. 2011;20:297-305.
69. Mahoney WM Jr, Fleming JN, Schwartz SM. A unifying hypothesis for scleroderma: identifying a target cell for scleroderma. Curr Rheumatol Rep. 2011;13:28-36.
70. Wei J, Bhattacharyya S, Tourtellotte WG, Varga J. Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy. Autoimmun Rev. 2011;10:267-275.
71. Omura T, Yoshiyama M, Matsumoto R, et al. Role of c-Jun NH2-terminal kinase inG-proteincoupled receptor agonist-induced cardiac plasminogen activator inhibitor-1 expression. J Mol Cell Cardiol. 2005;38:583-592.
72. Hao GH, Niu XL, Gao DF, Wei J, Wang NP. Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts. Br J Pharmacol. 2008;153:1409-1419.
73. Zyadeh FN, Sharma K, Erickson M, Wolf G. Stimulation of collagen gene expression and protein synthesis inmurinemesangial cells by high glucose in mediated by autocrine activation of transforming growth factor-?. J Clin Invest. 1994;93:536-542.
74. Martin J, Kelly DJ, Mifsud SA, et al. Tranilast attenuates cardiac matrix deposition in experimental diabetes: role of transforming growth factor ?. Cardiovasc Res. 2005;65:694-701.
75. Ohtsu H, Mifune M, Frank GD, et al. Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II. Arterioscler Thromb Vasc Biol. 2005;25:1831-1836.
76. Zhou H, Li YJ, Wang M, et al. Involvement of RhoA/ROCK in myocardial fibrosis in a rat model of type 2 diabetes. Acta Pharmacol Sin. 2011;32: 999-1008.
77. Greenhalgh SN, Conroy KP, Henderson NC. Healing scars: targeting pericytes to treat fibrosis. QJM. 2014.
78. Kelley C, D'Amore P, Hechtman HB, et al. Microvascular pericyte contractility in vitro: comparison with other cells of the vascular wall. J Cell Biol. 1987;104:483-490.
79. Shepro D, Morel NML. Pericyte physiology. FASEB J. 1993;7:1031-1038.
80. Rhodin JAG, Fujita H. Capillary growth in themesentery of normal young rats. Intravital video and electron microscope analyses. J Submicros Cytol Pathol. 1989;21:1-34.
81. Meyrick B, Fujiwara K, Reid L. Smooth muscle myosin in precursor and mature smooth muscle cells in normal pulmonary arteries and the effect of hypoxia. Exp Lung Res. 1981;2:303-313.
82. Shi X, HanW, Yamamoto H, et al. The cochlear pericytes. Microcirculation. 2008;15:515-529.
83. Joyce NC, Haire MF, Palade GE. Contractile proteins in pericytes. II. Immunocytochemical evidence for the presence of two isomyosins in graded concentrations. J Cell Biol. 1985a;100:1387-1395.
84. Joyce NC, Haire MF, Palade GE. Contractile proteins in pericytes. I. Immunoperoxidase localization of tropomyosin. J Cell Biol. 1985b;100: 1379-1386.
85. Williams M, Kerkar S, Tyburski JG, Steffes CP, Carlin AM, Wilson RF. The roles of cyclic adenosine monophosphate-and cyclic guanosine monophosphate-dependent protein kinase pathways in hydrogen peroxide-induced contractility of microvascular lung pericytes. J Trauma. 2003;55:677-682.
86. Fernández-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U. Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA. 2010;107(51):22290-22295.
87. Tsai MH, Jiang MJ. Rho-kinase-mediated regulation of receptor-agoniststimulated smoothmuscle contraction. Pflugers Arch. 2006;453:223-232.
88. Patel CA, Rattan S. Cellular regulation of basal tone in internal anal sphincter smooth muscle by RhoA/ROCK. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1747-G1756.
89. Kolyada AY, Riley KN, Herman IM. Rho GTPase signaling modulates cell shape and contractile phenotype in an isoactin-specific manner. Am J Physiol Cell Physiol. 2003;285:C1116-C1121.
90. Kutcher ME, Kolyada AY, Surks HK, Herman IM. Pericyte Rho GTPase mediates both pericyte contractile phenotype and capillary endothelial growth state. Am J Pathol. 2007;171:693-701.
91. Ferrati S, Fine D, You J, et al. Leveraging nanochannels for universal, zeroorder drug delivery in vivo. J Control Release. 2013;172(3):1011-1019.
92. Kloc M, Ghobrial RM. Chronic allograft rejection: a significant hurdle to transplant success. Burns Trauma. 2014;2:3-10.
93. Skelton ST, Tejpal N, Gong Y, Kloc M, Ghobrial RM. Downregulation of RhoA and changes in T cell cytoskeleton correlate with the abrogation of allograft rejection. Transpl Immunol. 2010;23:185-193.
94. Zhang L, Kloc M, Tejpal N, et al. ROCK1 inhibitor abrogates chronic rejection in rat cardiac model system. Open J Organ Transplant Surg. 2012;2:46-51.
95. Fuxe J, Tabruyn S, Colton K, et al. Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in sustained inflammation. Am J Pathol. 2011;178:2897-2909.
96. Gaengel K, Genove G, Armulik A, Betsholtz C. Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol. 2009;29:630-638.
97. Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell Res. 2009;19: 128-139.
98. Buijs JT, Stayrook KR, Guise TA. The role of TGF-? in bone metastasis: novel therapeutic perspectives. Bonekey Rep. 2012;1:96.
99. Chen S, Crawford M, Day RM, et al. RhoA modulates Smad signaling during transforming growth factor-beta-induced smooth muscle differentiation. J Biol Chem. 2006;281:1765-1770.
100. Heldin CH, Miyazono K, tenDijke P. TGF-beta signalling fromcellmembrane to nucleus through SMAD proteins. Nature. 1997;390:465-471.
101. Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Dev. 2005;19:2783-2810.
102. Sato Y, Rifkin DB. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 1989;109:309-315.
103. Urness LD, Sorensen LK, Li DY. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet. 2000;26:328-331.
104. Larsson J, Goumans MJ, Sjostrand LJ, et al. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J. 2001;20:1663-1673.
105. Lan Y, Liu B, Yao H, et al. Essential role of endothelial Smad4 in vascular remodeling and integrity. Mol Cell Biol. 2007;27:7683-7692.
106. Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A. (Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development. 1999;126: 1631-1642.
107. Gerhardt H, Betsholtz C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res. 2003;314:15-23.
108. Li F, Lan Y, Wang Y, et al. Endothelial Smad4 maintains cerebrovascular integrity by activating N-cadherin through cooperation with Notch. Dev Cell. 2011;20:291-302.
109. Goumans MJ, Valdimarsdottir G, Itoh S, et al. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling. Mol Cell. 2003;12:817-828.
110. Loughna S, Sato TN. Angiopoietin and Tie signaling pathways in vascular development. Matrix Biol. 2001;20:319-325.
111. Eklund L, Saharinen P. Angiopoietin signaling in the vasculature. Exp Cell Res. 2013;319:1271-1280.
112. Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF. Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest. 2002;82: 387-401.
113. Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME. The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008;49:2163-2171.
114. Patan S. TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res. 1998;56:1-21.
115. Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996;87:1171-1180.
116. Hammes HP, Lin J, Wagner P, et al. Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes. 2004;53:1104-1110.
117. Pfister F, Feng Y, vom Hagen F, et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008;57:2495-2502.
118. Tachibana K, Jones N, Dumont DJ, Puri MC, Bernstein A. Selective role of a distinct tyrosine residue on Tie2 in heart development and early hematopoiesis. Mol Cell Biol. 2005;25:4693-4702.
119. Jeansson M, Gawlik A, Anderson G, et al. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest. 2011;121:2278-2289.
120. Stratman AN, Malotte KM, Mahan RD, Davis MJ, Davis GE. Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood. 2009;114:5091-5101.
121. Cascone I, Audero E, Giraudo E, et al. Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1. Blood. 2003;102:2482-2490.
122. Olson LE, Soriano P. PDGFR? signaling regulates mural cell plasticity and inhibits fat development. Dev Cell. 2011;20:815-826.
123. Lin SL, Chang FC, Schrimpf C, et al. Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis. Am J Pathol. 2011;178:911-923.
124. Wang S, Cao C, Chen Z, et al. Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One. 2012;7:e45499.
125. Perrot V, Vazquez-Prado J, Gutkind JS. Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF. J Biol Chem. 2002;277:43115-43120.
126. Zhou H, Yang YH, Basile JR. The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4. Angiogenesis. 2014;17:261-274.
127. Yadav R, Larbi KY, Young RE, Nourshargh S. Migration of leukocytes through the vessel wall and beyond. Thromb Haemost. 2003;90:598-606.
128. Olson MF. Applications for ROCK kinase inhibition. Curr Opin Cell Biol. 2008;20:242-248.
129. http://www.selleckchem.com/ROCK.html.