Adenosine to inosine (A to I) editing is mediated by adenosine deaminases acting on RNA (ADAR) enzymes. Inosines are interpreted as guanosines by the translational machinery. Consequently, A to I editing in mRNAs can lead to their recoding and the formation of proteins not encoded in the genome. Filamin A is an actin-crosslinking protein. A to I editing in the filamin pre-mRNA leads to the exchange of a glutamine to an arginine in a highly interactive domain of the protein. However, the consequences of this editing event are still poorly understood. Here we show, using transgenic mice expressing either constitutively edited or constitutively uneditable filamin A that filamin A editing critically controls angiogenesis in tumors but also in a mouse ischemia model. Hyper-editing reduces angiogenesis, while hypoediting leads to increased angiogenesis, possibly by altering vascular endothelial growth factor receptor 2 (VEGFR2) turnover. Further, FLNA editing of the tumor itself seemingly affects its metastatic potential by changing its interaction with the extracellular matrix. We therefore identify filamin A editing as a critical component for angiogenesis, tumor growth, and metastasis formation.

Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH.

Vascular access is the lifeline for patients receiving haemodialysis as kidney replacement therapy. As a surgically created arteriovenous fistula (AVF) provides a high-flow conduit suitable for cannulation, it remains the vascular access of choice. In order to use an AVF successfully, the luminal diameter and the vessel wall of the venous outflow tract have to increase. This process is referred to as AVF maturation. AVF non-maturation is an important limitation of AVFs that contributes to their poor primary patency rates. To date, there is no clear overview of the overall role of the extracellular matrix (ECM) in AVF maturation. The ECM is essential for vascular functioning, as it provides structural and mechanical strength and communicates with vascular cells to regulate their differentiation and proliferation. Thus, the ECM is involved in multiple processes that regulate AVF maturation, and it is essential to study its anatomy and vascular response to AVF surgery to define therapeutic targets to improve AVF maturation. In this review, we discuss the composition of both the arterial and venous ECM and its incorporation in the three vessel layers: the tunica intima, media, and adventitia. Furthermore, we examine the effect of chronic kidney failure on the vasculature, the timing of ECM remodelling post-AVF surgery, and current ECM interventions to improve AVF maturation. Lastly, the suitability of ECM interventions as a therapeutic target for AVF maturation will be discussed.

Short-term preoperative methionine restriction (MetR) shows promise as a translatable strategy to modulate the body's response to surgical injury. Its application, however, to improve post-interventional vascular remodeling remains underexplored. Here, we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and adverse vascular remodeling after vein graft surgery. RNA sequencing reveals that MetR enhances the brown adipose tissue phenotype in arterial perivascular adipose tissue (PVAT) and induces it in venous PVAT. Specifically, PPAR-α was highly upregulated in PVAT-adipocytes. Furthermore, MetR dampens the post-operative pro-inflammatory response to surgery in PVAT-macrophages and . This study shows for the first time that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in browning of PVAT. Furthermore, we demonstrate the potential of short-term pre-operative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery.