- About EAS
By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief)
Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation
In atherosclerotic lesions, cholesterol-laden macrophage foam cells are formed and exposed to M1- and M2-polarizing factors. Da Silva et al. investigated the effects of M1- and M2-polarizing factors on the expression of pro- and anti-inflammatory genes in cultured human macrophage foam cells. To this purpose, human monocytes were differentiated into macrophages in the presence of M-CSF, and then converted into cholesterol-laden foam cells by incubation with acetylated LDL. The generated macrophages and foam cells were then polarized into the M1 phenotype by classical activation with LPS and IFN-γ, or into the M2 phenotype by alternative activation with IL-4. The authors showed that macrophages exposed to M1-polarizing factors responded by typical upregulation of several key proinflammatory genes (TNFA, IL1B, CXCL8, CCL19, and COX2), while the anti-inflammatory genes (MRC1, CCL17, and IL10) displayed variable responses.
In conclusion, conversion of cultured human macrophages into foam cells suppressed their pro-inflammatory responses to M1-polarizing factors. Thus, in the M1-polarizing microenvironment of atherosclerotic lesions, foam cell formation may locally weaken the macrophage-dependent inflammatory component of atherogenesis.
Experimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) directly promotes inflammatory processes contributing to atherosclerosis by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels.
Cheng et al. investigated the association between serum PCSK9 levels and the fraction and amount of necrotic core tissue in coronary atherosclerotic plaques, as assessed by intravascular ultrasound virtual histology (IVUS-VH) imaging.
Between 2008 and 2011, IVUS-VH imaging of non-culprit coronary arteries was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. PCSK9 concentrations were measured in serum samples obtained prior to coronary angiography. None of the patients received PCSK9 inhibitors.
Accurate quantification of atherosclerotic plaque volume by 3D vascular ultrasound using the volumetric linear array method
Direct quantification of atherosclerotic plaque volume by three-dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based three-dimensional (2D/3D) techniques generating pseudo-3D volumes from summed 2D plaque areas; however, its accuracy has not been reported. López-Melgar and collaborators determined the accuracy of 3DVUS for plaque volume measurement with special emphasis on small plaques, which is a hallmark of early atherosclerosis. The in vitro study was performed on nine phantoms of different volumes (small and medium-large) embedded at variable distances from the surface. The volumes determined by 3DVUS were compared with the real phantom volumes. The in vivo study was performed in a rabbit model of atherosclerosis, in which 3DVUS and 2D/3D volume measurements were correlated against gold-standard histological measurements.
Raal and colleagues investigated the clinical characteristics of 167 patients with HoFH from three recent international studies. The age of the patients ranged from 1 to 75 years, and a large proportion of them, both treated and untreated, exhibited LDL-C levels below the recommended clinical diagnostic threshold for HoFH, regardless the LDLR mutation status.
The authors concluded that HoFH is not restricted to very young patients or patients with extremely high LDL-C levels.
As highlighted in the accompanying commentary by Raul D. Santos, HoFH is more heterogeneous than previously thought. This heterogeneity and phenotypic overlap with heterozygous familial hypercholesterolaemia (HeFH) is important for clinical management. The phenotype rather than the genotype should be the physicians' main concern, and those subjects with the most severe phenotype should be more aggressively treated.