Key result
In an in vitro model of malignant hypertension, high pressure and hyperglycaemia induced Angiotensin-II production and apoptosis in mesangial cells, which subsequently triggered apoptosis in podocytes.
In an in vitro model of malignant hypertension, mesangial cells but not podocytes respond to high pressure by producing Angiotensin-II, which subsequently induces apoptosis in both cell types.
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Does not support clinical practice changes; leaves open whether mesangial Angiotensin-II drives podocyte loss in vivo.
AIM: Two populations of renal cells fully possess functional contractile cell apparatus: mesangial cells and podocytes. Previous studies demonstrated that in the context of malignant hypertension overproduction of Angiotensin-II by the contracting mesangial cells aggravated hypercellularity and apoptosis of adjacent cell populations. The role of podocytes in pathogenesis of malignant hypertension is unclear. We investigated responsiveness of normal vs. hyperglycaemic podocytes to pressure in a model of malignant hypertension. METHODS: Rat renal podocytes and mesangial cells were subjected to high hydrostatic pressure, using an in vitro model of malignant hypertension. Part of them was pre-exposed to hyperglycaemic medium. Alternatively, the cells were cultured in conditioned medium collected from mesangial cells pre-exposed to pressure. RESULTS: Angiotensin-II was significantly increased in normoglycaemic mesangial cells subjected to pressure, triggering enhanced proliferation and apoptosis. No augmented Angiotensin-II, proliferation or apoptosis were evident in pressure-exposed normoglycaemic podocytes. In hyperglycaemic mesangial cells, but not podocytes, basal Angiotensin-II and apoptosis were augmented, along with abrogated proliferation. Challenge with exogenous Angiotensin-II or Angiotensin-II-containing conditioned medium, induced apoptosis both in podocytes and mesangial cells. CONCLUSIONS: 1. Unlike mesangial cells, podocytes do not respond to high pressure or hyperglycaemia per se. Resultantly, neither high pressure nor hyperglycaemia, trigger apoptosis of podocytes in vitro. However, surplus of Angiotensin-II, amply produced in vivo by the adjacent mesangial cells, would seem to be sufficient for initiating apoptosis of both mesangial cells and podocytes. 2. Hyperglycaemia abrogates cell replication. Resultantly, in diabetic patients regeneration of renal tissue damaged by the incidence of malignant hypertension may become compromised or completely lost.
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Berman et al. (2013) studied Malignant hypertension. High hydrostatic pressure and/or hyperglycaemic medium vs. Normoglycaemic and normal pressure conditions was evaluated on Angiotensin-II levels, proliferation, and apoptosis. In an in vitro model of malignant hypertension, high pressure and hyperglycaemia induced Angiotensin-II production and apoptosis in mesangial cells, which subsequently triggered apoptosis in podocytes.
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