title: Incomplete Restoration of Angiotensin II-Induced Renal Extracellular Matrix Deposition and Inflammation Despite Complete Functional Recovery in Rats.
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.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Anne-Roos S
authors.initials: AR
authors.lastname: Frenay
authors.affiliation: Department of Nephrology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Saleh
authors.initials: S
authors.lastname: Yazdani
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Boersema
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands; Department of Obstetrics and Gynecology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Anne Marijn
authors.initials: AM
authors.lastname: van der Graaf
authors.affiliation: Department of Nephrology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Waanders
authors.affiliation: Department of Nephrology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.affiliation: Department of Nephrology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003893:Desmin; D000804:Angiotensin II; D003094:Collagen