- About EAS
By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief)
Circulating levels of low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) are two of the most important risk factors for the development of cardiovascular disease (CVD), the leading cause of death worldwide.
The most well studied of these miRNAs, miR-33, has been demonstrated to target ABCA1, as well as numerous other genes involved in metabolic function and RCT, and therapeutic inhibition of miR-33 was found to increase HDL levels in mice and non-human primates.
Moreover, numerous studies have demonstrated the beneficial effects of miR-33 inhibition or knockout in reducing atherosclerotic plaque burden. Even a more recent work has identified miRNAs that regulate LDL cholesterol levels, including direct modulation of LDL uptake in the liver through targeting of the LDL receptor. Among these, inhibition of miR-128-1, miR-148a, or miR-185 was found to reduce plasma LDL levels, and inhibition of miR-185 was further demonstrated to reduce atherosclerotic plaque size in ApoE−/− mice.
Highlighted articlesBoshuizen et al. investigated the involvement of myeloid IFNγ signalling in murine atherosclerosis. Bone marrow was isolated from interferon gamma receptor 2 chain (IFNγR2) wild type and myeloid IFNγR2 deficient mice and injected into lethally irradiated LDLR-/- mice. After recovery, mice were put on a high-fat diet for 10 weeks. Atherosclerotic lesion analysis was then performed and the accompanying liver inflammation assessed.
The results show that even though absence of myeloid IFNγ signalling attenuated the myeloid IFNγ response, no significant differences in atherosclerotic lesion size or phenotype were found. In addition, no effects of IFNγR2 deficiency could be observed, when examining the liver inflammatory state.
Overall, the data presented argue against a role of myeloid IFNγR2 in atherosclerosis development.
Cosegregation of serum cholesterol with cholesterol intestinal absorption markers in families with primary hypercholesterolemia without mutations in LDLR, APOB, PCSK9 and APOE genes
The genetic cause and pathogenic mechanism of approximately 20–40% of autosomal dominant hypercholesterolemias (ADH) are unknown. Increased cholesterol intestinal absorption has been associated with ADH. Whether this variation contributes to their pathogenesis is unknown.
They showed that concentrations of cholestanol, sitosterol, campesterol and stigmasterol are higher in affected than in non-affected subjects. In addition, there was a strong co-segregation of hyperabsorption with high LDL cholesterol within hyperabsorber families. In hyperabsorber families, 60.5% of subjects were hyperabsorbers and 76% of them had high LDL cholesterol versus 38.3% and 63% in non-hyperabsorber families, respectively.
In conclusion, most hypercholesterolemic family members with a hyperabsorber proband are hyperabsorbers. These absorption markers are significantly and positively associated with LDL cholesterol, and predispose to high LDL cholesterol in family members.
Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression
n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists on whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD.
Bathia et al. tested whether 15–18-month n-3 PUFA treatment [docosahexaenoic acid (DHA) and eicosapentaenoic acid] versus placebo decrease carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. In addition, they evaluated whether improvement in markers of NAFLD severity is associated with decreased CIMT progression over time.
In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.
92 patients completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005–0.020 mm) compared to 0.015 mm (IQR 0.007–0.025 mm) in the placebo group (n = 47). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat, reduced CK-18 levels, and antihypertensive usage in multivariable regression analysis after adjusting for all potential confounders. Decreased weight and increased DHA tissue enrichment during the 18-month study were both independently associated with decreased liver fat, but not with CK-18.
Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries – Findings from the EUROASPIRE IV survey
Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD.
The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event, from hospitals throughout Europe and how the intake of these drugs was reported by the patients, when they were seen more than one year later, in relationship with their achieved LDL-C levels.