Endothelial injury and dysfunction in ischemic acute renal failure

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50%. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs. In addition, adenosine triphosphate depletion studies in cultured endothelial cells have demonstrated that multiple actin-based alterations occur in a reversible and duration-dependent fashion. After an ischemic insult, total renal blood flow returns toward normal, but marked, regional alterations occur. Most affected is the outer medullary or corticomedullary junction region where blood flow remains approximately 10% of normal. In this area, the microvasculature becomes congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and extravasation all contribute to this congestion. Increased expression of both P selectin and E selectin has been documented in renal endothelial cells after ischemic injury, and treatment with antibodies to either intercellular adhesion molecule-1, P selectins, or E selectins has been shown to minimize renal injury. During ischemia in vivo and adenosine triphosphate depletion in cell culture studies, F-actin destruction occurs, with polymerization leading to accumulation of intracellular actin aggregates. By using multiphoton microscopy, Voxx software, and the Tie-2 mouse with selective endothelial cell green fluorescent protein expression driven by the Tie-2 promoter, we have been able to identify macrovascular and microvascular endothelial cells in four dimensions (three dimensions plus time) intravitally. By using Texas red-labeled large molecular weight dextrans, we can document blood flow and vascular dysfunction. Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs.

Original languageEnglish
JournalCritical Care Medicine
Volume30
Issue number5 SUPPL.
StatePublished - 2002

Fingerprint

Acute Kidney Injury
Endothelial Cells
Wounds and Injuries
Actins
P-Selectin
E-Selectin
Ischemia
Adenosine Triphosphate
Kidney
Tight Junctions
Renal Circulation
Intercellular Adhesion Molecule-1
Blister
Microvessels
Green Fluorescent Proteins
Dextrans
Vascular Smooth Muscle
Polymerization
Smooth Muscle Myocytes
Blood Vessels

Keywords

  • Acute renal failure
  • Endothelium
  • Hypoxia
  • Ischemia
  • Multiphoton microscopy

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Endothelial injury and dysfunction in ischemic acute renal failure. / Molitoris, Bruce; Sandoval, Ruben; Sutton, Timothy.

In: Critical Care Medicine, Vol. 30, No. 5 SUPPL., 2002.

Research output: Contribution to journalArticle

@article{cb845c235558413ebf87f27ec4dd480b,
title = "Endothelial injury and dysfunction in ischemic acute renal failure",
abstract = "Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50{\%}. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs. In addition, adenosine triphosphate depletion studies in cultured endothelial cells have demonstrated that multiple actin-based alterations occur in a reversible and duration-dependent fashion. After an ischemic insult, total renal blood flow returns toward normal, but marked, regional alterations occur. Most affected is the outer medullary or corticomedullary junction region where blood flow remains approximately 10{\%} of normal. In this area, the microvasculature becomes congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and extravasation all contribute to this congestion. Increased expression of both P selectin and E selectin has been documented in renal endothelial cells after ischemic injury, and treatment with antibodies to either intercellular adhesion molecule-1, P selectins, or E selectins has been shown to minimize renal injury. During ischemia in vivo and adenosine triphosphate depletion in cell culture studies, F-actin destruction occurs, with polymerization leading to accumulation of intracellular actin aggregates. By using multiphoton microscopy, Voxx software, and the Tie-2 mouse with selective endothelial cell green fluorescent protein expression driven by the Tie-2 promoter, we have been able to identify macrovascular and microvascular endothelial cells in four dimensions (three dimensions plus time) intravitally. By using Texas red-labeled large molecular weight dextrans, we can document blood flow and vascular dysfunction. Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs.",
keywords = "Acute renal failure, Endothelium, Hypoxia, Ischemia, Multiphoton microscopy",
author = "Bruce Molitoris and Ruben Sandoval and Timothy Sutton",
year = "2002",
language = "English",
volume = "30",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "5 SUPPL.",

}

TY - JOUR

T1 - Endothelial injury and dysfunction in ischemic acute renal failure

AU - Molitoris, Bruce

AU - Sandoval, Ruben

AU - Sutton, Timothy

PY - 2002

Y1 - 2002

N2 - Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50%. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs. In addition, adenosine triphosphate depletion studies in cultured endothelial cells have demonstrated that multiple actin-based alterations occur in a reversible and duration-dependent fashion. After an ischemic insult, total renal blood flow returns toward normal, but marked, regional alterations occur. Most affected is the outer medullary or corticomedullary junction region where blood flow remains approximately 10% of normal. In this area, the microvasculature becomes congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and extravasation all contribute to this congestion. Increased expression of both P selectin and E selectin has been documented in renal endothelial cells after ischemic injury, and treatment with antibodies to either intercellular adhesion molecule-1, P selectins, or E selectins has been shown to minimize renal injury. During ischemia in vivo and adenosine triphosphate depletion in cell culture studies, F-actin destruction occurs, with polymerization leading to accumulation of intracellular actin aggregates. By using multiphoton microscopy, Voxx software, and the Tie-2 mouse with selective endothelial cell green fluorescent protein expression driven by the Tie-2 promoter, we have been able to identify macrovascular and microvascular endothelial cells in four dimensions (three dimensions plus time) intravitally. By using Texas red-labeled large molecular weight dextrans, we can document blood flow and vascular dysfunction. Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs.

AB - Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50%. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs. In addition, adenosine triphosphate depletion studies in cultured endothelial cells have demonstrated that multiple actin-based alterations occur in a reversible and duration-dependent fashion. After an ischemic insult, total renal blood flow returns toward normal, but marked, regional alterations occur. Most affected is the outer medullary or corticomedullary junction region where blood flow remains approximately 10% of normal. In this area, the microvasculature becomes congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and extravasation all contribute to this congestion. Increased expression of both P selectin and E selectin has been documented in renal endothelial cells after ischemic injury, and treatment with antibodies to either intercellular adhesion molecule-1, P selectins, or E selectins has been shown to minimize renal injury. During ischemia in vivo and adenosine triphosphate depletion in cell culture studies, F-actin destruction occurs, with polymerization leading to accumulation of intracellular actin aggregates. By using multiphoton microscopy, Voxx software, and the Tie-2 mouse with selective endothelial cell green fluorescent protein expression driven by the Tie-2 promoter, we have been able to identify macrovascular and microvascular endothelial cells in four dimensions (three dimensions plus time) intravitally. By using Texas red-labeled large molecular weight dextrans, we can document blood flow and vascular dysfunction. Intravital studies using multiphoton imaging techniques can now be conducted to identify and quantify endothelial cell injury and dysfunction in functioning organs.

KW - Acute renal failure

KW - Endothelium

KW - Hypoxia

KW - Ischemia

KW - Multiphoton microscopy

UR - http://www.scopus.com/inward/record.url?scp=0036245205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036245205&partnerID=8YFLogxK

M3 - Article

VL - 30

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 5 SUPPL.

ER -