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Incomplete Restoration of Angiotensin II-Induced Renal Extracellular Matrix Deposition and Inflammation Despite Complete Functional Recovery in Rats.

Frenay AR, Yazdani S, Boersema M, van der Graaf AM, Waanders F, van den Born J, Navis GJ, van Goor H - PLoS ONE (2015)

Bottom Line: Eight weeks after cessation of Ang II, all clinical parameters, pre-fibrotic changes such as myofibroblast transformation and increase in lymph vessel number (lymphangiogenesis) returned to control values.However, glomerular desmin expression, glomerular and periglomerular macrophages and interstitial collagens remained elevated.These dormant abnormalities indicate that after transient renal function decline, inflammation and collagen deposition may persist despite normalization of the initiating pathophysiological stimulus perhaps rendering the kidney more vulnerable to further damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.

ABSTRACT
Some diseases associated with a temporary deterioration in kidney function and/or development of proteinuria show an apparently complete functional remission once the initiating trigger is removed. While it was earlier thought that a transient impairment of kidney function is harmless, accumulating evidence now suggests that these patients are more prone to developing renal failure later in life. We therefore sought to investigate to what extent renal functional changes, inflammation and collagen deposition are reversible after cessation of disease induction, potentially explaining residual sensitivity to damage. Using a rat model of Angiotensin II (Ang II)-induced hypertensive renal disease we show the development of severe hypertension (212 ± 10.43 vs. 146 ± 1.4 mmHg, p<0.001) and proteinuria (51.4 ± 6.3 vs. 14.7 ± 2.0 mg/24h, p<0.01) with declined creatinine clearance (2.0 ± 0.5 vs. 4.9 ± 0.6 mL/min, p<0.001) to occur after 3 weeks of Ang II infusion. At the structural level, Ang II infusion resulted in interstitial inflammation (18.8 ± 4.8 vs. 3.6 ± 0.5 number of macrophages, p<0.001), renal interstitial collagen deposition and lymphangiogenesis (4.1 ± 0.4 vs. 2.2 ± 0.4 number of lymph vessels, p<0.01). Eight weeks after cessation of Ang II, all clinical parameters, pre-fibrotic changes such as myofibroblast transformation and increase in lymph vessel number (lymphangiogenesis) returned to control values. However, glomerular desmin expression, glomerular and periglomerular macrophages and interstitial collagens remained elevated. These dormant abnormalities indicate that after transient renal function decline, inflammation and collagen deposition may persist despite normalization of the initiating pathophysiological stimulus perhaps rendering the kidney more vulnerable to further damage.

No MeSH data available.


Related in: MedlinePlus

Regression of lymph vessels after Ang II withdrawal, no effect on peritubular capillaries.Ang II infusion increased mRNA expression of PDPN, however this was not significant (A). Ang II-induced lymphangiogenesis was evidenced by an increase in lymph vessel formation (B), with spontaneous regression to control levels eight weeks after withdrawal of Ang II. Ang II infusion had no effects on peritublar capillaries (C). Representative photomicrographs of Podoplanin stained renal sections (D). (##p<0.01 vs. control at time of biopsy; ***p<0.001 vs. Ang II at time of biopsy)
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pone.0129732.g011: Regression of lymph vessels after Ang II withdrawal, no effect on peritubular capillaries.Ang II infusion increased mRNA expression of PDPN, however this was not significant (A). Ang II-induced lymphangiogenesis was evidenced by an increase in lymph vessel formation (B), with spontaneous regression to control levels eight weeks after withdrawal of Ang II. Ang II infusion had no effects on peritublar capillaries (C). Representative photomicrographs of Podoplanin stained renal sections (D). (##p<0.01 vs. control at time of biopsy; ***p<0.001 vs. Ang II at time of biopsy)

Mentions: Under Ang II infusion the mRNA expression level of PDPN, a marker of lymphatic vessels (LV), was upregulated; however this was not significant (Fig 11A). Stopping Ang II infusion resulted in a decrease of PDPN mRNA expression to control levels. Ang II infusion induced a 2-fold increase in the number of LVs (4.1 ± 0.4 vs. 2.2 ± 0.4, p<0.01) (Fig 11B). At termination, the number of LVs of former Ang II infused rats regressed to control levels (p<0.001). Ang II infusion had no effects on the number of peritubular capillaries (Fig 11C).


Incomplete Restoration of Angiotensin II-Induced Renal Extracellular Matrix Deposition and Inflammation Despite Complete Functional Recovery in Rats.

Frenay AR, Yazdani S, Boersema M, van der Graaf AM, Waanders F, van den Born J, Navis GJ, van Goor H - PLoS ONE (2015)

Regression of lymph vessels after Ang II withdrawal, no effect on peritubular capillaries.Ang II infusion increased mRNA expression of PDPN, however this was not significant (A). Ang II-induced lymphangiogenesis was evidenced by an increase in lymph vessel formation (B), with spontaneous regression to control levels eight weeks after withdrawal of Ang II. Ang II infusion had no effects on peritublar capillaries (C). Representative photomicrographs of Podoplanin stained renal sections (D). (##p<0.01 vs. control at time of biopsy; ***p<0.001 vs. Ang II at time of biopsy)
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4464893&req=5

pone.0129732.g011: Regression of lymph vessels after Ang II withdrawal, no effect on peritubular capillaries.Ang II infusion increased mRNA expression of PDPN, however this was not significant (A). Ang II-induced lymphangiogenesis was evidenced by an increase in lymph vessel formation (B), with spontaneous regression to control levels eight weeks after withdrawal of Ang II. Ang II infusion had no effects on peritublar capillaries (C). Representative photomicrographs of Podoplanin stained renal sections (D). (##p<0.01 vs. control at time of biopsy; ***p<0.001 vs. Ang II at time of biopsy)
Mentions: Under Ang II infusion the mRNA expression level of PDPN, a marker of lymphatic vessels (LV), was upregulated; however this was not significant (Fig 11A). Stopping Ang II infusion resulted in a decrease of PDPN mRNA expression to control levels. Ang II infusion induced a 2-fold increase in the number of LVs (4.1 ± 0.4 vs. 2.2 ± 0.4, p<0.01) (Fig 11B). At termination, the number of LVs of former Ang II infused rats regressed to control levels (p<0.001). Ang II infusion had no effects on the number of peritubular capillaries (Fig 11C).

Bottom Line: Eight weeks after cessation of Ang II, all clinical parameters, pre-fibrotic changes such as myofibroblast transformation and increase in lymph vessel number (lymphangiogenesis) returned to control values.However, glomerular desmin expression, glomerular and periglomerular macrophages and interstitial collagens remained elevated.These dormant abnormalities indicate that after transient renal function decline, inflammation and collagen deposition may persist despite normalization of the initiating pathophysiological stimulus perhaps rendering the kidney more vulnerable to further damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.

ABSTRACT
Some diseases associated with a temporary deterioration in kidney function and/or development of proteinuria show an apparently complete functional remission once the initiating trigger is removed. While it was earlier thought that a transient impairment of kidney function is harmless, accumulating evidence now suggests that these patients are more prone to developing renal failure later in life. We therefore sought to investigate to what extent renal functional changes, inflammation and collagen deposition are reversible after cessation of disease induction, potentially explaining residual sensitivity to damage. Using a rat model of Angiotensin II (Ang II)-induced hypertensive renal disease we show the development of severe hypertension (212 ± 10.43 vs. 146 ± 1.4 mmHg, p<0.001) and proteinuria (51.4 ± 6.3 vs. 14.7 ± 2.0 mg/24h, p<0.01) with declined creatinine clearance (2.0 ± 0.5 vs. 4.9 ± 0.6 mL/min, p<0.001) to occur after 3 weeks of Ang II infusion. At the structural level, Ang II infusion resulted in interstitial inflammation (18.8 ± 4.8 vs. 3.6 ± 0.5 number of macrophages, p<0.001), renal interstitial collagen deposition and lymphangiogenesis (4.1 ± 0.4 vs. 2.2 ± 0.4 number of lymph vessels, p<0.01). Eight weeks after cessation of Ang II, all clinical parameters, pre-fibrotic changes such as myofibroblast transformation and increase in lymph vessel number (lymphangiogenesis) returned to control values. However, glomerular desmin expression, glomerular and periglomerular macrophages and interstitial collagens remained elevated. These dormant abnormalities indicate that after transient renal function decline, inflammation and collagen deposition may persist despite normalization of the initiating pathophysiological stimulus perhaps rendering the kidney more vulnerable to further damage.

No MeSH data available.


Related in: MedlinePlus