RT Journal Article
T1 Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis
A1 Gonzalo-Gil, Elena
A1 Toldos González, Óscar
A1 Pablos Álvarez, José Luis
A1 Galindo Izquierdo, María
AB Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice. Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA. Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels. Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.
PB Frontiers
SN 1664-3224
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/114214
UL https://hdl.handle.net/20.500.14352/114214
LA eng
NO Gonzalo-Gil E, García-Herrero C, Toldos O, Usategui A, Criado G, Pérez-Yagüe S, Barber DF, Pablos JL, Galindo M. Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis. Front Immunol. 2018 Aug 28;9:1948.
NO Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (PI10/01102, RETICS RD12/009 RIER, and Miguel Servet program CP13/00014 to GC)
NO Fundación Española de Reumatología (FER2010)
NO European Regional Development Fund (FEDER)
NO Spanish Ministry of Economy, Industry and Competitiveness (SAF-2014-54057-R to DB).
DS Docta Complutense
RD 10 abr 2025