English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Atherosclerosis has been defined as an inflammatory disease developing primarily at arterial branching points and curvatures, where disturbed flow constantly inflicts low-grade injury to the endothelial monolayer lining the vessel wall. This step seems to be crucial for atheroprogression, because the maladaptation of endothelial cells (ECs) to this physiological disturbance increases the susceptibility of branching points to a proinflammatory state. Consequently, maladapted ECs make arterial branching points more prone to circulating and oxidized low-density lipoproteins (oxLDLs) influx in the subendothelial space, and promote the recruitment of monocytes by releasing proinflammatory molecules (i.e., chemokine and adhesion molecules). Subendothelial monocytes differentiate intomacrophages,which locally proliferate and take up oxLDL. Exacerbation of lipid deposition into the plaque leads to insufficient lipoprotein scavenging by macrophages, which turn into foam cells. Advanced lesion progression is characterized by an accumulation of lipoproteins, macrophage-derived foam cell apoptosis and necrosis due to defective efferocytosis, formationofcholesterolcrystals, andsmoothmusclecell (SMC) cap formation. Hence, growing of advanced lesions leads to a critical reduction of arterial lumen and blood flow, reduced oxygensupply, andruptureorerosionof theplaques,whichcan cause thrombosis. Byanalyzingaforementionedphasesofplaquedevelopment, it has become evident that inflammation plays a crucial role in atheroprogression. It is thereforenotsurprising thatmanyof the therapies currently used to treat atherosclerosis and thrombus formation focus on counteracting the onset of an acute inflammatory state. Notably, statins are capable not only of lowering cholesterol levels but also to exert anti-inflammatory effects. Accordingly, studies conducted using colchicine, canakinumab, an antibody to interleukin (IL)-1β, or other modalities targeting IL-6 or IL-1 receptors are aimed at more specifically reducing inflammatory activity during atherosclerosis.1 However, current anti-inflammatory and antithrombotic therapies are far from lacking side effects, although the risk–benefit ratio still makes them an indispensable choice improving the life expectancy of patients with cardiovascular diseases. The exponential growth of genome-wide association studies (GWAS), single-cell sequencing databases, and context-based text mining has brought to light the existence of complex regulatory networks triggering cardiovascular disease. Among these, the heterogeneity and interconnection of vascular cell populations, as well as their selective contribution to distinct stages of atherosclerosis particularly stand out (►Fig. 1). Moreover, GWAS have shown disease-linked genetic variation in the nonprotein-coding sequence space, which are actively transcribed to noncoding ribonucleic acids (ncRNAs), that is, microand long ncRNAs (miRNAs and lncRNAs). This novel class of ncRNAs is differentially expressed in diseased tissues and act as epigenetic modulators of gene expression. Indeed, the Part 2 of the Theme Issue on atherosclerosis and atherothrombosis brings together the innovative and provocative view of expert scientists on novel therapeutic perspectives. Among these, the identification of phenotypeand cell-to-cell interactionrelated molecules, as well as epigenetic modulatory-related molecules, as novel and selective therapeutic targets to treat atherosclerosis. Review articles by Busygina et al2 and Pircher et al3 underscore a fundamental problem with current immunotherapies. Indeed, antiplatelet and collagen inhibitors, such as thefirst-inclass oral irreversible Bruton tyrosine kinase (Btk) inhibitors

Next-Generation Therapeutic Concepts for Atherosclerosis: Focus on Cell Specificity and Noncoding RNAs