The Mechanism of Increased Vascular Permeability in Renal Ischemic Reperfusion Injury: Potential Role of Angiopoietin-1 and Hyaluronan
Adis Tasanarong MD*,***, Sookkasem Khositseth MD**, Supachai Thitiarchakul MD*
Affiliation : * Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Klong Nung, Klong Luang, Pathumtani, Thailand ** Department of Paediatric, Faculty of Medicine, Thammasat University (Rangsit Campus), Klong Nung, Klong Luang, Pathumtani, Thailand *** Inter-Department of Biomedical Sciences, Graduate School, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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.
Material and Method: 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 hr post-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.
Conclusion : 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.
Keywords : Angiopoietin-1, Hyaluronic acid, Ischemia, Kidney diseases, Reperfusion injury
