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Atherosclerosis is a long-term, chronic inflammatory disease of the vessel wall leading to the formation of occlusive or rupture-prone lesions in large arteries. Complications of atherosclerosis can become severe and lead to cardiovascular diseases (CVD) with lethal consequences. During the last three decades, chemokines and their receptors earned great attention in the research of atherosclerosis as they play a key role in development and progression of atherosclerotic lesions. They orchestrate activation, recruitment, and infiltration of immune cells and subsequent phenotypic changes, e.g., increased uptake of oxidized low-density lipoprotein (oxLDL) by macrophages, promoting the development of foam cells, a key feature developing plaques. In addition, chemokines and their receptors maintain homing of adaptive immune cells but also drive pro-atherosclerotic leukocyte responses. Recently, specific targeting, e.g., by applying cell specific knock out models have shed new light on their functions in chronic vascular inflammation. This article reviews recent findings on the role of immunomodulatory chemokines in the development of atherosclerosis and their potential for targeting.

Genome-wide association studies (GWAS) have established a link between the genomic locus 10q11, which hosts the CXCL12 gene, and the risk for coronary artery disease (CAD) (1). CAD risk alleles downstream of CXCL12 have been associated with plasma levels of the chemokine CXCL12 (2); however, the nature and directionality of this association remain elusive. Recently, a Mendelian randomization study identifying genetic determinants of biomarkers in the populations of ORIGIN and CARDIoGRAM revealed CXCL12 as a causal mediator of CAD, supported by epidemiological analysis showing a 15% higher risk for cardiovascular events per SD of increased CXCL12 plasma levels in ORIGIN (3). To detail the association between CXCL12 and CAD, we conducted a meta-analysis of GWAS performed in the EPIC-Norfolk and PROMIS cohorts (n=12,657; filters: INFO≥0.5, MAF≥0.01, HWE≥1×10 −6 , only SNPs appearing in both cohorts). The study was approved by an institutional review committee and subjects gave informed consent. Applying conditional analysis, we newly identified rs2802492, an intergenic SNP near CXCL12, to be independently associated with CXCL12 plasma levels (β=0.016, P=3.24×10 −8) as determined by ELISA (α-isoform, R&D Systems Quantikine kit) (2) and with increased risk for CAD (OR 1.047, P=1.27×10 −6), corroborating CXCL12 as a driver of CAD. No linkage disequilibrium (r 2 >0.8) was found between rs2802492 and the CAD-associated SNPs rs1746048 (1) and intergenic rs1482478 (3). Notably, when specifically tested for

The global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

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