MicroRNA‐126 is a Marker of Vascular Dysfunction in Human ANCA Vasculitis
Authors: Scullion Kathleen M. , Vliegenthart Bastiaan A.D. , Farrah Tariq E. , Dhaun Neeraj , Dear James W. 
Published: June 2021

Vascular dysfunction and kidney disease commonly co‐exist and their presence substantially increases the risk of cardiovascular disease. There is an unmet clinical need for biomarkers that specifically report vascular health and injury. MicroRNAs (miRs) change in disease states and some are tissue specific which makes them an attractive reservoir for circulating biomarker discovery. MiR‐126 is endothelial cell‐enriched and present throughout the vasculature. Antineutrophil cytoplasmic antibody (ANCA) vasculitis is a rare disease, primarily affecting the vasculature, which often injures the kidneys resulting in rapidly progressive glomerulonephritis. It represents a tractable model of acute vascular and kidney injury in humans. We examined the relationship between miR‐126 and vascular dysfunction in patients with ANCA vasculitis.

Patients presenting with ANCA vasculitis were recruited at the Royal Infirmary of Edinburgh, UK. Inclusion criteria were seropositivity for ANCA and organ‐threatening disease requiring immunosuppression. The study was approved by the local research ethics committee and performed in accordance with the Declaration of Helsinki. Plasma samples were collected from patients with vasculitis at initial disease presentation (pre‐treatment), and at disease remission (post‐treatment) (n=70 paired). Samples were also collected from patients with chronic kidney disease (CKD), a group known to have chronic vascular dysfunction (n=37), and healthy subjects (n=56). The concentration of a panel of circulating microRNAs were measured by qRT‐PCR and absolute quantification was performed using a standard curve. Results were correlated with clinical parameters currently used to assess vascular function. Statistical significance was determined by Mann‐Whitney U test or Wilcoxon matched‐pairs signed rank test.

In ANCA vasculitis, pre‐treatment circulatory miR‐126 was reduced compared to post‐treatment: pre‐treatment median 0.08fM (IQR 0.03–0.32fM), post‐treatment median 0.30fM (IQR 0.06–1.12fM), P=0.0015. In patients with CKD, the concentration of miR‐126 was higher than in patients with ANCA vasculitis pre‐treatment, median 1.96fM (IQR 0.81–4.66fM), P<0.0001. MiR‐126 was substantially higher in healthy subjects than in pre‐treatment vasculitis patients, median 8.46fM (IQR 1.90–185.10fM), P<0.0001 and CKD patients (P=0.0011). MicroRNA species that are not expressed in the vasculature did not differ across the groups. The increase in the circulating concentration of miR‐126 from pre‐treatment to post‐treatment correlated with estimated glomerular filtration rate (eGFR), a key clinical indicator of kidney function (r=0.60, P<0.0001).

MicroRNA‐126 is a novel circulating biomarker that might report vascular injury and response to treatment in patients with vasculitis. With further development and refinement, microRNA‐126 could prove to be a valuable marker for diagnosis and tracking disease progression to ensure effective treatment.

Support or Funding Information

Supported by the British Heart Foundation.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.