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Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury
K F Hilgers1, A Hartner, M Porst
1Department of Medicine IV, University of Erlangen-Nürnberg, Erlangen; Max-Delbrück-Center, Berlin-Buch, Germany. karl.hilgers@rzmail.uni-erlangen.de
Background:
We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (MPhi) infiltration.
Methods:
Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial MPhis were counted.
Results:
In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant MPhi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, MPhis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize blood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial MPhi infiltration significantly.
Conclusion:
MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to MPhi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.
Insights
Monocyte chemoattractant protein-1 (MCP-1) is elevated in hypertensive nephrosclerosis, correlating with macrophage infiltration. Angiotensin II type 1 receptor blockade reduces MCP-1 induction and macrophage infiltration in these models.
Area of Science:
- Nephrology
- Cardiovascular Research
- Inflammation Biology
Background:
- Hypertensive nephrosclerosis involves kidney damage due to high blood pressure.
- Monocyte chemoattractant protein-1 (MCP-1) is a key chemokine involved in inflammatory responses.
- Macrophage infiltration plays a significant role in the progression of kidney disease.
Purpose of the Study:
- To investigate MCP-1 expression in hypertensive nephrosclerosis.
- To determine the effect of angiotensin II type 1 receptor blockade on MCP-1 expression.
- To assess the impact on macrophage infiltration in the kidneys.
Main Methods:
- Utilized two-kidney, one-clip (2K1C) hypertensive rats and various spontaneously hypertensive rat strains.
- Administered valsartan, an angiotensin II type 1 receptor antagonist.
- Quantified MCP-1 expression via Northern/Western blots and immunohistochemistry.
- Counted glomerular and interstitial macrophages.
Main Results:
- MCP-1 expression was elevated in the nonclipped kidney of 2K1C rats, coinciding with macrophage infiltration.
- MCP-1 was detected in various kidney cells, including macrophages.
- Valsartan treatment reduced blood pressure, blocked MCP-1 induction, and decreased macrophage infiltration.
- MCP-1 expression was not increased in all hypertensive models studied (SHR, SHR-SP).
Conclusions:
- MCP-1 expression is upregulated in angiotensin II-dependent hypertensive nephrosclerosis models.
- MCP-1 upregulation is temporally and spatially linked to macrophage infiltration.
- The angiotensin II type 1 receptor is crucial for mediating MCP-1 induction in this context.