Angiopoietin-2 a new treatment target for kidney fibrosis

Chronic Kidney Disease (CKD) affects more than 10% of the general population worldwide (1). It is characterized by kidney fibrosis, a progressive process that destroys the kidney (2). An effective treatment to stop the progression of CKD is still lacking. Scientists have now discovered a potential mean to treat CKD by inhibiting Angiopoietin-2 (ANG2), a vascular growth factor (3). Angiopoietin-2 is a potential new treatment target for kidney fibrosis in CKD.

Angiopoietin-2 a new treatment target for kidney fibrosis in CKD

Patients with chronic kidney disease (CKD) have increased plasma levels of Angiopoietin-2 (ANG2).  Studies have shown that ANG2 induces kidney injury and fibrosis in patients with CKD as well as in mouse models of kidney disease (3).  Preventing the progression of renal fibrosis by blocking Angiopoietin-2 could be a new approach in treating chronic kidney disease-associated pathologies.

Based on data of the recent study from Chang et al., on the application of an Angiopoietin-2 inhibitor to mouse models of progressive kidney disease, the scientists found a profound inhibitory effects of ANG2 inhibition on macrophage infiltration and fibrosis (3).  

Future clinical studies will be required to investigate the therapeutic potential on the protective effect of Angiopoietin-2 inhibition on progressive kidney disease. Read more: Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells.

BIOMEDICA developed two assays for the accurate measurement of ANGIOPOIETIN-2 

Mouse / rat ANGIOPOIETIN-2 ELISA  (cat. no. BI-ANG2MR)

• only 5µl sample volume /well
• no predilution of samples required
• kit control included
• sample values provided

 

Human ANGIOPOIETIN-2 ELISA (cat. no. BI-ANG2)

• only 20µl sample volume /well
• the assay is optimized for clinical samples – sample values provided
• ready to use standards and controls  included

 

References

1. Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study. Sundström J, Bodegard J, Bollmann A, Vervloet MG, Mark PB, Karasik A, Taveira-Gomes T, Botana M, Birkeland KI, Thuresson M, Jäger L, Sood MM, VanPottelbergh G, Tangri N; CaReMe CKD Investigators. Lancet Reg Health Eur. 2022 Jun 30;20:100438. doi: 10.1016/j.lanepe.2022.100438. PMID: 36090671; PMCID: PMC9459126.

2. Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences. Panizo S, Martínez-Arias L, Alonso-Montes C, Cannata P, Martín-Carro B, Fernández-Martín JL, Naves-Díaz M, Carrillo-López N, Cannata-Andía JB. Int J Mol Sci. 2021 Jan 2;22(1):408. doi: 10.3390/ijms22010408. PMID: 33401711; PMCID: PMC7795409.

3. Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells. Chang FC, Liu CH, Luo AJ, Tao-Min Huang T, Tsai MH, Chen YJ, Lai CF, Chiang CK, Lin TH, Chiang WC, Chen YM, Chu TS, Lin SL. Kidney Int. 2022 Oct;102(4):780-797. doi: 10.1016/j.kint.2022.06.026. Epub 2022 Aug 4. PMID: 35934136.

Abstract

Plasma levels of angiopoietin-2 are increased in patients with chronic kidney disease (CKD). Moreover, mouse models of progressive kidney disease also demonstrate increased angiopoietin-2 in both plasmas and kidneys. The role of dysregulated angiopoietins in the progression of kidney disease has not been thoroughly investigated. Here, we found in a cohort of 319 patients with CKD that plasma angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratios were positively associated with the development of kidney failure. In mice with progressive kidney disease induced by either ureteral obstruction or ischemia-reperfusion injury, overexpression of human angiopoietin-1 in the kidney tubules not only reduced macrophage infiltration in the initial stage post-injury but also attenuated endothelial cell apoptosis, microvascular rarefaction, and fibrosis in the advanced disease stage. Notably, angiopoietin-1 attenuated chemokine C-C motif ligand 2 (CCL2) expression in the endothelial cells of the fibrosing kidneys, and these protective effects led to attenuation of functional impairment. Mechanistically, angiopoietin-1 reduced CCL2-activated macrophage migration and protected endothelial cells against cell apoptosis induced by angiopoietin-2 and Wnt ligands. Based on this, we applied L1-10, an angiopoietin-2 inhibitor, to the mouse models of progressive kidney disease and found inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis. Thus, we defined the detrimental impact of increased angiopoietin-2 on kidney survival of patients with CKD which appears highlighted by angiopoietin-2 induced endothelial CCL2-activated macrophage infiltration and endothelial cell apoptosis in their kidneys undergoing fibrosis.

Further reading

New therapeutic targets in chronic kidney disease progression and renal fibrosis. Rayego-Mateos S, Valdivielso JM. Expert Opin Ther Targets. 2020 Jul;24(7):655-670. doi: 10.1080/14728222.2020.1762173. Epub 2020 May 18. PMID: 32338087.