Summary
Endothelial responses to stressors are nonuniform and follow the rules of stress-induced
hormesis. Responses to the same stressor, depending on its intensity, can range from
pro-regenerative to pro-lethal. Exposure to sublethal stressors induces a programmed
response that results in stress resistance, whereas a lethal level of a stressor accelerates
cell demise. Diverse stressors turn on several default programs within the cells;
such programs tend to induce anti-oxidative defenses and anti-inflammatory and pro-survival
systems, whereas others tend to switch on pro-apoptotic systems. The response of the
kidney endothelium to various forms of acute kidney injury follows these general principles.
It is characterized by a proinflammatory pattern that includes up-regulation of different
adhesion molecules promoting endothelial–leukocyte interactions, generation of reactive
oxygen species, with formation of oxidative and nitrosative stress and mitochondrial
damage. Simultaneously, a series of adaptive mechanisms, both local and systemic,
are ignited. Stressed endothelial cells broadcast distress signals systemically; these
signals can be directed toward the restoration of homeostasis or aggravation of the
original insult.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Seminars in NephrologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Endothelial cell heterogeneity.Crit Care Med. 2003; 31: S221-S230
- Renal Anatomy and histology.in: Jennette J.C. Olson J.L. Schwartz M.M. Silva F.G. Heptinstall's pathology of the kidney. 6th ed. Lippincott Williams & Wilkins, Philadelphia, PA2006: 1-70
- Endothelial cells in physiology and in the pathophysiology of vascular disorders.Blood. 1998; 91: 3527-3561
- Molecular basis of endothelial dysfunction in sepsis.Cardiovasc Res. 2003; 60: 49-57
- Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities.Antioxidants Redox Signaling. 2008; 10: 1713-1765
- VEGF expression in hypoxia and hyperglycemia: reciprocal effect on branching angiogenesis in epithelial-endothelial co-cultures.J Am Soc Nephrol. 2002; 13: 2027-2036
- Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities.Development. 2004; 131: 1847-1857
- SCUBE-1, a novel developmental gene involved in renal regeneration and repair.Nephrol Dial Transplant. 2010; 25: 1421-1428
- A morphometric study of arterial intimal thickening in kidneys of dialyzed patients.Am J Pathol. 1979; 95: 597-610
- Increased shear stress-released NO and decreased endothelial calcium in rat isolated perfused juxtamedullary nephrons.Kidney Int. 2005; 67: 227-236
- The vascular pathology of thrombotic thrombocytopenic purpura.Lab Invest. 1966; 15: 927-946
- Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries.J Am Soc Nephrol. 1999; 10: 2208-2214
- Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal hypoxic tubular injury debate revisited.Kidney Int. 2010; 77: 9-16
- Stress-response hormesis and aging: “that which does not kill us makes us stronger.”.Cell Metab. 2008; 7: 200-203
- The concept of cellular “fight-or-flight” reaction to stress.Am J Physiol Renal Physiol. 2001; 280: F551-F561
- Temporary disruption of the plasma membrane is required for c-fos expression in response to mechanical stress.Mol Biol Cell. 1999; 10: 1247-1257
- Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues.Bioessays. 2000; 22: 911-919
- Growth factors are released by mechanically wounded endothelial cells.J Cell Biol. 1989; 109: 811-822
- Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides.Am J Physiol. 1993; 265: C577-C606
- Nrf2-Keap1 defines a physiologically important stress response mechanism.Trends Mol Med. 2004; 10: 549-557
- Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1.J Biol Chem. 2006; 281: 324-333
- Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.Cell. 1999; 98: 115-124
- Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators.Mol Cell Biol. 2005; 25: 1354-1366
- Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation.PLoS One. 2008; 3 (e2009)
- Activation and signaling by the AMP-activated protein kinase in endothelial cells.Circ Res. 2009; 105: 114-127
- Endoplasmic reticulum stress and renal disease.Antioxidants Redox Signaling. 2009; 11: 2341-2352
- Role of cardiolipin in cytochrome c release from mitochondria.Cell Death Differ. 2007; 14: 1243-1247
- Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment.J Cell Mol Med. 2011; 15: 668-678
- Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells.Circ Res. 2001; 88: 167-174
- Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization.Blood. 2003; 102: 1340-1346
- Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.Nature Med. 2004; 10: 858-864
- Ischemia-induced exocytosis of Weibel-Palade bodies mobilizes stem cells.J Am Soc Nephrol. 2008; 19: 2321-2330
- Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro.Blood. 2004; 104: 2761-2766
- Endothelial progenitor cell-derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA.Blood. 2007; 110: 2440-2448
- Glomerular actions of endothelin in vivo.J Clin Invest. 1989; 83: 1762-1767
- Nitric oxide and endothelins—novel autocrine paracrine regulators of the circulation.Semin Nephrol. 1991; 11: 169-185
- Role of endothelin in cyclosporine-induced glomerular dysfunction.Kidney Int. 1990; 37: 1487-1491
- Intracellular ramification of the endothelin signal.Am J Physiol. 1991; 260: C982-C992
- Kynurenine is an endothelium-derived relaxing factor produced during inflammation.Nat Med. 2010; 16: 279-287
- Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.Cell. 1997; 88: 277-285
- Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1.J Biol Chem. 2002; 277: 16464-16469
- Hypoxia-induced increase of endostatin in murine aorta and lung.Histochem Cell Biol. 2006; 125: 497-508
- Chronic NOS inhibition actuates endothelial-mesenchymal transformation.Am J Physiol. 2007; 292: H285-H294
- The role of cell swelling in ischemic renal damage and the protective effect of hypertonic solute.J Clin Invest. 1972; 51: 118-126
- Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.J Clin Invest. 1996; 97: 1056-1063
- Dissociation of tubular cell detachment and tubular cell death in clinical and experimental “acute tubular necrosis.”.Lab Invest. 1991; 64: 546-556
- Ischemic acute renal failure: an inflammatory disease?.Kidney Int. 2004; 66: 480-485
- Cell adhesion molecules in renal injury.in: Schnellmann R. Comprehensive toxicology. Vol 7. Elsevier Ltd, Republic of Suriname, South America2010: 813-845
- Two novel probes reveal tubular and vascular Arg-Gly-Asp (RGD) binding sites in the ischemic rat kidney.Kidney Int. 1997; 52: 93-102
- Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.Am J Physiol Renal Physiol. 2002; 282: F1140-F1149
- Injury of the renal microvascular endothelium alters barrier function after ischemia.Am J Physiol Renal Physiol. 2003; 285: F191-F198
- In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia.J Clin Invest. 1996; 97: 2377-2383
- Atomic force microscopy measurement of leukocyte-endothelial interaction.Am J Physiol Heart Circ Physiol. 2004; 286: H359-H367
- Cyclic arginine-glycine-aspartic acid peptide inhibits macrophage infiltration of the kidney and carotid artery lesions in apo-E-deficient mice.Am J Physiol Renal Physiol. 2006; 290: F159-F166
- Pathophysiology of AKI: injury and normal and abnormal repair.Contrib Nephrol. 2010; 165: 9-17
- Scavenging of peroxynitrite ameliorates lipid peroxidation and DNA damage in experimental ischemic acute renal failure.Am J Physiol Renal Physiol. 2001; 281: F948-F957
- Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice.Am J Physiol. 1999; 277: F383-F390
- Intravital videomicroscopy of peritubular capillaries in renal ischemia.Am J Physiol Renal Physiol. 2002; 282: F1150-F1155
- Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia.Am J Physiol Renal Physiol. 2004; 287: F621-F627
- Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic acute kidney injury.Am J Physiol Renal Physiol. 2008; 295: F351-F359
- Oxidative and nitrosative stress in acute renal ischemia.Am J Physiol Renal Physiol. 2001; 281: F948-F957
- Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat.Kidney Int. 2000; 58: 658-673
- Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney.Kidney Int. 2004; 65: 1714-1723
- Activation of mitochondrial biogenesis by hormesis.Circ Res. 2008; 103: 1191-1193
- The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy.Biochim Biophys Acta. 1998; 1366: 177-196
- Superoxide flashes in single mitochondria.Cell. 2008; 134: 279-290
- Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models.J Clin Invest. 2009; 119: 1275-1285
- Mitochondrial dysfunction and type 2 diabetes.Science. 2005; 307: 384-387
Article info
Footnotes
Financial support: Supported in part by National Institutes of Health grants DK54602, DK052783, and DK45462 (M.S.G.), the Westchester Artificial Kidney Foundation (M.S.G.), and the start-up fund from the Department of Pathology, The Ohio State University (S.V.B.).
Conflict of interest statement: none.
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
