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Abstract: SA-PO373

Malignant Hypertension Induced Vicious Circle Culminating in Podocyte Detachment

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation


  • Abu hamad, Ramzia, Assaf Harofeh Medical Center, Zerifin, Israel
  • Beberashvili, Ilia, Assaf Harofeh Medical Center, Zerifin, Israel
  • Efrati, Shai, Assaf Harofeh Medical Center, Zerifin , Israel

. Renal injuries induced by increased intra-glomerular pressure coincide with podocyte damage and proteinuria. In a previous study we have demonstrated that in a direct response to pressure, podocytes increase Angiotensin-II levels and via AT1 receptors to structural changes in adhesion proteins, culminating in viable podocyte detachment. The aim of this study was to further investigate the pathophysiologic effect of malignant hypertension on podocyte mitochondrial functions, NOX4, SOD2 and inflammatory mediators.


Human Podocyte cells were exposed to high hydrostatic pressure for 1h, to mimic the incidence of malignant hypertension. Podocytes were placed in mesangial cell media pre-exposed to pressure to simulate the paracrine effect. Mitochondrial function, NOX4, SOD2, Angiotensin-II, inflammatory mediators, integrinβ1 expression and Podocyte detachment were evaluated.


Pressure enforcement decreased mitochondrial membrane potential accompanied by a reduction of SOD2. Moreover, augmented detachment of viable/apoptotic podocytes with decrease expression of integrins β1, mediated via AT1/AT2, was induced by the high pressure. Mesangial pre-exposed to pressure release exaggerated amounts of Angiotensin-II and TGFβ1. Podocytes placed in this mesangial media induced an inflammatory flare-up increase via TGFβ1 and Il-6. In addition, an increase of NOX4 and decline of SOD2 resulted in mitochondrial membrane potential decrease mediated via AT1/AT2 leading to apoptosis.


Malignant hypertension, induced mitochondrial dysfunction combined with structural changes and detachment of Podocyte mediated by increase Angiotensin-II. The paracrine effect, mediated by increasing production of Angiotensin-II by the mesangial cells, increase apoptosis and enhance mitochondrial dysfunction via decrease SOD2, activation of NOX4 and flare-up of inflammatory mediators.