Injury of the renal microvascular endothelium alters barrier function after ischemia

Abstract

The role of renal microvascular endothelial cell injury in the pathophysiology of ischemic acute renal failure (ARF) remains largely unknown. No consistent morphological alterations have been ascribed to the endothelium of the renal microvasculature as a result of ischemia-reperfusion injury. Therefore, the purpose of this study was to examine biochemical markers of endothelial injury and morphological changes in the renal microvascular endothelium in a rodent model of ischemic ARF. Circulating von Willebrand factor (vWF) was measured as a marker of endothelial injury. Twenty-four hours after ischemia, circulating vWF peaked at 124% over baseline values ( P = 0.001). The FVB-TIE2/GFP mouse was utilized to localize morphological changes in the renal microvascular endothelium. Immediately after ischemia, there was a marked increase in F-actin aggregates in the basal and basolateral aspect of renal microvascular endothelial cells in the corticomedullary junction. After 24 h of reperfusion, the pattern of F-actin staining was more similar to that observed under physiological conditions. In addition, alterations in the integrity of the adherens junctions of the renal microvasculature, as demonstrated by loss of localization in vascular endothelial cadherin immunostaining, were observed after 24 h of reperfusion. This observation temporally correlated with the greatest extent of permeability defect in the renal microvasculature as identified using fluorescent dextrans and two-photon intravital imaging. Taken together, these findings indicate that renal vascular endothelial injury occurs in ischemic ARF and may play an important role in the pathophysiology of ischemic ARF.

Soluble Thrombomodulin Protects Ischemic Kidneys

“…The extent of leakage of HMWD was less than that of LMWD, as previously observed. 7 Extravasation scores after ischemia in the salinetreated animals were 5.29 Ϯ 4.5 and 0.48 Ϯ 0.17, respectively, for LMWD and HMWD. The extravasation score (0.50 Ϯ 0.62) and the extent of leakage of the LMWD in the sTMtreated animals were significantly less than that observed in the saline-treated animals after ischemia (n ϭ 3, P Ͻ 0.05; Figure 6B).…”

“…2,4 Regional alterations in kidney blood flow persist after ischemic injury and play a central role in the extension of ischemic injury during reperfusion. [5][6][7] Congestion of the renal microcirculation, especially in the capillaries of the outer medullary vasa recta, contribute to deficits in oxygen and substrate delivery. 5 Evidence suggests a major role for endothelial dysfunction and microvascular alterations during the course of ischemic AKI.…”

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

“…Decreased HDL anti‐inflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease 32, 33, 34, 35. Each of these processes (systemic inflammation, oxidative stress, and endothelial dysfunction and damage) plays a key role in the pathogenesis of AKI 9, 11, 35, 36, 37. Therefore, in an analogous manner to their role in chronic kidney dysfunction, these HDL functional capacities could contribute to postoperative renal function and AKI.…”

Renal Hemodynamics in AKI

“…23 Rodent models of ischemia-reperfusion show compromised peritubular perfusion characterized by sluggish and retrograde blood flow that develops within minutes after reperfusion 24,25 followed by restoration of normal flow within the first 4 hours, only to dramatically worsen over the next 20 hours. 21,26 Similarly, rodent models of acute endotoxemia suggest that cortical peritubular capillaries are among the first renal structures injured. [27][28][29][30] Interestingly, despite an apparent full recovery of renal function at 48 hours, functional capillary density recovered only partially.…”