Epigenetically regulated inflammation in vascular senescence and renal progression of chronic kidney disease

Abstract

Chronic kidney disease (CKD) and its complications, including vascular senescence and progressive renal fibrosis, are associated with inflammation. Vascular senescence, in particular, has emerged as an instrumental mediator of vascular inflammation that potentially worsens renal function. Epigenetically regulated inflammation involving histone modification, DNA methylation, actions of microRNAs and other non-coding RNAs, and their reciprocal reactions during vascular senescence and inflammaging are underappreciated. Their synergistic effects can contribute to CKD progression. Vascular senotherapeutics or pharmacological anti-senescent therapies based on epigenetic machineries can therefore be plausible options for ameliorating vascular aging and even halting the worsening of renal fibrosis. These include histone deacetylase modulators, histone methyltransferase modulators, other histone modification effectors, DNA methyltransferase inhibitors, telomerase reverse transcriptase enhancers, microRNA mimic delivery, and small molecules with microRNA-regulating potentials. Some of these molecules have already been tested and have shown anecdotal evidence for treating uremic vasculopathy and renal fibrosis, supporting the feasibility of this approach.

Keywords: Chronic kidney disease; DNA methylation; Epigenetics; Histone modification; MicroRNA; Uraemia; Vascular inflammation; Vascular senescence.