Abstract
Cardiovascular epigenomics is a relatively young field of research, yet it is providing novel insights into gene regulation in the atherosclerotic arterial wall. That information is already pointing to new avenues for atherosclerosis (AS) prevention and therapy. In parallel, advances in nanoparticle (NP) technology allow effective targeting of drugs and bioactive molecules to the vascular wall. The partnership of NP technology and epigenetics in AS is just beginning and promises to produce novel exciting candidate treatments. Here, we briefly discuss the most relevant recent advances in the two fields. We focus on AS and DNA methylation, as the DNA methylome of that condition is better understood in comparison with the rest of the cardiovascular disease field. In particular, we review the most recent advances in NP-based delivery systems and their use for DNA methylome modification in inflammation. We also address the promises of DNA methyltransferase inhibitors for prevention and therapy. Furthermore, we emphasize the unique challenges in designing therapies that target the cardiovascular epigenome. Lastly, we touch the issue of human exposure to industrial NPs and its impact on the epigenome as a reminder of the undesired effects that any NP-based therapy must avoid to be apt for secondary prevention of AS.
Highlights
Drug loading to nanoparticles (NPs) allows targeting to specific cells and tissues and generally increases drug potency
Small apolipoprotein B-containing low-density lipoprotein particles have been identified as highly atherogenic [9]. These early events are followed by infiltration of monocyte-derived macrophages, an inflammatory response aimed at scavenging excess vascular wall oxidized lipoproteins [10]
Basic research is fast deepening our knowledge of the vascular wall epigenome in health and disease, pointing to therapeutic targets, whether genomewide or in specific loci
Summary
Drug loading to nanoparticles (NPs) allows targeting to specific cells and tissues and generally increases drug potency. The latter is achieved by combinations of improved biodistribution, solubility, site-release characteristics, circulation half-life, bioavailability, and immunogenicity (for a recent general review of the topic, see [1]). The relevance of EPR in cardiovascular disease is not well understood [2]. The best understood epigenetic modification of DNA is methylation, the focus of this article. Cardiogenetics 2022, 12 regulates gene expression in a context-dependent manner. Cellular DNAm profiles are tightly regulated during differentiation and participate in establishing tissue-specific gene expression, but stochastic changes in DNAm due to epigenetic drift occur [5,6,7]. The literature was chosen among entries obtained by PubMed email alert with the ‘nanoparticle atherosclerosis’ and ‘nanoparticle’ search terms
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