The mechanism of increased vascular permeability in renal ischemic reperfusion injury: potential role of angiopoietin-1 and hyaluronan.
BACKGROUND
One striking feature observed during renal ischemia reperfusion injury (IRI) is the increase in interstitial fluid and infiltration, which reflects an increase in vascular permeability. Angiopoietin-1 (Ang-1) prevents vascular leakage and inflammation. Hyaluronic acid (HA) has a high capacity to bind and retain water and is pro-inflammatory factor.


METHODS
The authors evaluated the expression of Ang-1 and HA during renal IRI bilaterally for 30 minutes. Renal tissue was sent for pathologic study, proteins expression, and mRNA in renal IRI at 24 and 48 hr.


RESULTS
At 24 hr post-injury, histopathology studies revealed severe tubular epithelial cell (TEC) necrosis, peritubular capillary (PTC) congestion, mild interstitial infiltration, and edema. Histopathology at 48 hr post-injury showed a progressive increased degree of PTC congestion, interstitial infiltration and edema. In normal kidney, Ang-1 was abundant in glomerulus and PTC patterns, while HA is absent in the cortex but present in the medulla. At 24 and 48 h rpost-IRI, kidney cortex and medulla showed a reduced Ang-1 staining but with an increase in HA staining. Western blot analysis showed that levels of Ang-1 expression decreased to 44% of normal levels at 24 hr post-IRI and further declined to 31% at 48 hr post-IRI. Using real time RT-PCR, Ang-1 expression declined to 15% of normal levels at 24 hr post-IRI and sustained at 48 hr post-IRI.


CONCLUSIONS
These results suggest that lowered Ang-1 expression levels and increased HA may contribute to an increased permeability and inflammation of microcirculation in renal IRI.
Tasanarong
Adis
A
Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Klong Nung, Klong Luang, Pathumtani, Thailand. adis_tasanarong@hotmail.com
Khositseth
Sookkasem
S
Thitiarchakul
Supachai
S
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D012333:RNA, Messenger; D006820:Hyaluronic Acid