Your browser doesn't support javascript.
loading
Myeloid CCR2 Promotes Atherosclerosis after AKI.
Hüsing, Anne M; Wulfmeyer, Vera C; Gaedcke, Svenja; Fleig, Susanne V; Rong, Song; DeLuca, David; Haller, Hermann; Schmitt, Roland; von Vietinghoff, Sibylle.
Afiliación
  • Hüsing AM; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
  • Wulfmeyer VC; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
  • Gaedcke S; German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
  • Fleig SV; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
  • Rong S; Nephrology Section, Medical Clinic 1, University Hospital Bonn, Rheinische Friedrich Wilhelm University of Bonn, Bonn, Germany.
  • DeLuca D; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
  • Haller H; German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
  • Schmitt R; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
  • von Vietinghoff S; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
J Am Soc Nephrol ; 33(8): 1487-1500, 2022 Aug.
Article en En | MEDLINE | ID: mdl-35537780
BACKGROUND: The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms. METHODS: Atherosclerotic lesions and inflammation were investigated in native and bone marrow-transplanted LDL receptor-deficient (LDLr-/- ) mice after unilateral renal IR injury using histology, flow cytometry, and gene expression analysis. RESULTS: Aortic root atherosclerotic lesions were significantly larger after renal IR injury than in controls. A gene expression screen revealed enrichment for chemokines and their cognate receptors in aortas of IR-injured mice in early atherosclerosis, and of T cell-associated genes in advanced disease. Confocal microscopy revealed increased aortic macrophage proximity to T cells. Differential aortic inflammatory gene regulation in IR-injured mice largely paralleled the pattern in the injured kidney. Single-cell analysis identified renal cell types that produced soluble mediators upregulated in the atherosclerotic aorta. The analysis revealed a marked early increase in Ccl2, which CCR2+ myeloid cells mainly expressed. CCR2 mediated myeloid cell homing to the post-ischemic kidney in a cell-individual manner. Reconstitution with Ccr2-/- bone marrow dampened renal post-ischemic inflammation, reduced aortic Ccl2 and inflammatory macrophage marker CD11c, and abrogated excess aortic atherosclerotic plaque formation after renal IR. CONCLUSIONS: Our data introduce an experimental model of remote proatherogenic effects of renal IR and delineate myeloid CCR2 signaling as a mechanistic requirement. Monocytes should be considered as mobile mediators when addressing systemic vascular sequelae of kidney injury.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión / Aterosclerosis / Lesión Renal Aguda / Placa Aterosclerótica Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión / Aterosclerosis / Lesión Renal Aguda / Placa Aterosclerótica Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania