Renal Endothelial Injury and Microvascular Dysfunction in Acute Kidney Injury

Overview

Journal Semin Nephrol

Specialty Nephrology

Date 2015 Mar 22

PMID 25795503

Citations 103

Authors

Sudhanshu Kumar Verma

Bruce A Molitoris

Affiliations

Soon will be listed here.

Abstract

The kidney is comprised of heterogeneous cell populations that function together to perform a number of tightly controlled, complex and interdependent processes. Renal endothelial cells contribute to vascular tone, regulation of blood flow to local tissue beds, modulation of coagulation and inflammation, and vascular permeability. Both ischemia and sepsis have profound effects on the renal endothelium, resulting in microvascular dysregulation resulting in continued ischemia and further injury. In recent years, the concept of the vascular endothelium as an organ that is both the source of and target for inflammatory injury has become widely appreciated. Here we revisit the renal endothelium in the light of ever evolving molecular advances.

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References

Vollmar B, Glasz J, Leiderer R, Post S, Menger M . Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. Am J Pathol. 1994; 145(6):1421-31. PMC: 1887483. View

Gerhardt H, Betsholtz C . Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res. 2003; 314(1):15-23. DOI: 10.1007/s00441-003-0745-x. View

Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G . Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010; 9(11):883-97. DOI: 10.1038/nrd3248. View

Ballermann B . Glomerular endothelial cell differentiation. Kidney Int. 2005; 67(5):1668-71. DOI: 10.1111/j.1523-1755.2005.00260.x. View

Murakami M . Signaling required for blood vessel maintenance: molecular basis and pathological manifestations. Int J Vasc Med. 2011; 2012:293641. PMC: 3236483. DOI: 10.1155/2012/293641. View

Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai C . Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction. Am J Physiol Renal Physiol. 2010; 299(5):F1056-64. PMC: 2980406. DOI: 10.1152/ajprenal.00070.2010. View

Silldorff E, Pallone T . Adenosine signaling in outer medullary descending vasa recta. Am J Physiol Regul Integr Comp Physiol. 2001; 280(3):R854-61. DOI: 10.1152/ajpregu.2001.280.3.R854. View

Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J . Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science. 2002; 296(5566):346-9. DOI: 10.1126/science.1070238. View

Vaporciyan A, DeLisser H, Yan H, Mendiguren I, Thom S, Jones M . Involvement of platelet-endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo. Science. 1993; 262(5139):1580-2. DOI: 10.1126/science.8248808. View

10.

Goeckeler Z, Wysolmerski R . Myosin light chain kinase-regulated endothelial cell contraction: the relationship between isometric tension, actin polymerization, and myosin phosphorylation. J Cell Biol. 1995; 130(3):613-27. PMC: 2120532. DOI: 10.1083/jcb.130.3.613. View

11.

Pallone T, Silldorff E . Pericyte regulation of renal medullary blood flow. Exp Nephrol. 2001; 9(3):165-70. DOI: 10.1159/000052608. View

12.

Lindahl P, Johansson B, Leveen P, Betsholtz C . Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997; 277(5323):242-5. DOI: 10.1126/science.277.5323.242. View

13.

Carpenter C . Actin cytoskeleton and cell signaling. Crit Care Med. 2000; 28(4 Suppl):N94-9. DOI: 10.1097/00003246-200004001-00011. View

14.

Fontenot J, Gavin M, Rudensky A . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6. DOI: 10.1038/ni904. View

15.

Dichtl W, Dulak J, Frick M, Alber H, Schwarzacher S, Ares M . HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2003; 23(1):58-63. DOI: 10.1161/01.atv.0000043456.48735.20. View

16.

Laudes I, Chu J, Huber-Lang M, Guo R, Riedemann N, Sarma J . Expression and function of C5a receptor in mouse microvascular endothelial cells. J Immunol. 2002; 169(10):5962-70. DOI: 10.4049/jimmunol.169.10.5962. View

17.

Chen Y, Chang F, Wu C, Chou Y, Hsu H, Chiang W . Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. Kidney Int. 2011; 80(11):1170-81. DOI: 10.1038/ki.2011.208. View

18.

Crawford C, Kennedy-Lydon T, Sprott C, Desai T, Sawbridge L, Munday J . An intact kidney slice model to investigate vasa recta properties and function in situ. Nephron Physiol. 2012; 120(3):p17-31. PMC: 5166522. DOI: 10.1159/000339110. View

19.

London N, Zhu W, Bozza F, Smith M, Greif D, Sorensen L . Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci Transl Med. 2010; 2(23):23ra19. PMC: 2875996. DOI: 10.1126/scitranslmed.3000678. View

20.

Edwards A, Cao C, Pallone T . Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta. Am J Physiol Renal Physiol. 2010; 300(2):F441-56. PMC: 3044008. DOI: 10.1152/ajprenal.00499.2010. View