Subjects with familial hypercholesterolemia are characterized by an inflammatory phenotype despite long-term intensive cholesterol lowering treatment.

Objective: The atherosclerotic process is driven by elevated Low-density lipoprotein (LDL)-cholesterol in combination with enhanced inflammatory responses. Several mediators participate in this complex inflammatory network including members of the tumour necrosis factor (receptor) superfamily. Familial hypercholesterolemia (FH) is associated with increased risk of developing premature atherosclerosis.

Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype.

Background: Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies.

Objective: To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels.

Methods And Results: Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited.

Low level of inflammatory marker in hyperhomocysteinemic patients on statin therapy.

Inflammatory processes including increased activation of chemokines play an important role in atherogenesis. Patients with hyperhomocysteinemia have increased risk for cardiovascular events that potentially involve enhanced inflammation. Statins may have anti-inflammatory actions at least partly independent on their lipid-lowering effects.

Cholesterol efflux mediators in homozygous familial hypercholesterolemia patients on low-density lipoprotein apheresis.

Background: Homozygous familial hypercholesterolemia (FH) is a rare disorder that may affect 1 person per million. Early initiation of aggressive cholesterol-lowering therapy is essential to prevent premature coronary heart disease. Selective removal of low-density lipoprotein (LDL) by LDL apheresis is a reliable method of treatment.

Maternal familial hypercholesterolaemia (FH) confers altered haemostatic profile in offspring with and without FH.

Introduction: Patients with familial hypercholesterolaemia (FH) are characterized by high total and LDL cholesterol. Pregnant women with FH have higher absolute levels of total and LDL cholesterol, and a more pro-coagulant pattern compared with healthy pregnant women. Maternal hypercholesterolaemia has been shown to affect early atherosclerosis formation in the offspring.

Elevated serum MMP-9/TIMP-1 ratio in patients with homozygous familial hypercholesterolemia: effects of LDL-apheresis.

Objective: Matrix degradation within an atherosclerotic plaque is an important pathogenic factor in atherosclerosis, and is largely modulated by the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors (i.e., tissue inhibitor of MMPs [TIMPs]).

Apheresis in homozygous familial hypercholesterolemia: the results of a follow-up of all Norwegian patients with homozygous familial hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH), which affects 1 in a million individuals, leads to extremely elevated levels of cholesterol and early-onset cardiovascular disease.

Objective: The aim of this study was to assess all 7 HoFH patients treated with low-density lipoprotein (LDL) apheresis in Norway with respect to quality of life, clinical and laboratory assessments, and cardiovascular status.

Methods: Apheresis treatment and assessment of cardiovascular status was performed at local hospitals but coordinated by the Lipid Clinic that has followed all patients since diagnosis.

Lipoprotein(a) levels in coronary heart disease-susceptible and -resistant patients with familial hypercholesterolemia.

Objective: Familial hypercholesterolemia (FH) is caused by defects in genes coding for proteins involved in low density lipoprotein (LDL) metabolism, and is associated with increased risk of premature coronary heart disease (CHD). The clinical phenotype of FH exhibits marked variability due to additional metabolic and environmental factors, and further biomarkers are required for appropriate risk assessment. The aim of the present study was to search for risk markers among FH patients.

Children with familial hypercholesterolemia are characterized by an inflammatory imbalance between the tumor necrosis factor α system and interleukin-10.

Objective: Familial hypercholesterolemia (FH) is associated with increased risk of premature atherosclerosis. Increasing evidence supports involvement of inflammation in atherogenesis. The inflammatory cytokine tumor necrosis factor (TNF)α has been regarded as a key mediator in the development of atherosclerosis due to its involvement in several stages in this process.

Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe).

Background: The liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ⁻/⁻ mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies.

Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins.

Homocysteine has been related to increased risk of CVD. Matrix degradation and inflammation may be involved in this link between hyperhomocysteinaemia and CVD. Recent studies suggest that cystatin C can modulate matrix degradation and inflammation.

Dysregulated RANK ligand/RANK axis in hyperhomocysteinemic subjects: effect of treatment with B-vitamins.

Background And Purpose: Homocysteine has been linked to increased risk of ischemic stroke and other cardiovascular events. Matrix degradation and inflammation play an important role in these disorders, and we have demonstrated increased levels of matrix-degrading enzymes and inflammatory cytokines in hyperhomocysteinemic individuals. Recent studies suggest that RANK ligand (RANKL) through interaction with its receptor RANK can modulate matrix degradation and inflammation.

The antiatherogenic function of HDL is impaired in hyperhomocysteinemic subjects.

High plasma homocysteine concentrations have been associated with increased risk of cardiovascular disease, whereas plasma HDL concentration is inversely correlated to such disorders. We hypothesized that hyperhomocysteinemic subjects may have dysfunctional HDL. We therefore investigated the ability of serum from hyperhomocysteinemic male and female subjects (n = 10) and control subjects (n = 10) to induce cholesterol efflux and to inhibit release of inflammatory mediators from human umbilical vein endothelial cell.

Impaired inhibitory effect of interleukin-10 on the balance between matrix metalloproteinase-9 and its inhibitor in mononuclear cells from hyperhomocysteinemic subjects.

Background And Purpose: Homocysteine has been linked to increased risk of ischemic stroke and other cardiovascular events, but the mechanism by which elevated plasma levels of homocysteine promotes atherogenesis remains unclear. Matrix degradation, partly regulated by the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), plays an important role in atherogenesis and plaque destabilization, and we hypothesized an imbalance between MMPs and TIMPs in hyperhomocysteinemia.

Methods: Serum MMP-9 and TIMP-1 was measured in 12 hyperhomocysteinemic and 12 control subjects.

Triglyceride-rich HDL3 from patients with familial hypercholesterolemia are less able to inhibit cytokine release or to promote cholesterol efflux.

Familial hypercholesterolemia (FH) is associated with heterogeneity of the onset and severity of coronary heart disease (CHD). In this study, we investigated different low-grade proinflammatory markers and the atheroprotective function of the HDL3 subfraction in FH-patients (n = 13) with identical LDL-receptor mutations and in age- and sex-matched healthy controls (n = 11). Compared with healthy controls, FH-patients had greater gene expressions of the proatherogenic mediators TNF-alpha and IL-8 in circulating peripheral blood mononuclear cells.

Chemokines in children with heterozygous familiar hypercholesterolemia: selective upregulation of RANTES.

Objective: Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia.

Methods And Results: We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs) from clinically healthy children with and without heterozygous familial hypercholesterolemia (FH).

Hyperhomocysteinemic subjects have enhanced expression of lectin-like oxidized LDL receptor-1 in mononuclear cells.

An elevated plasma concentration of homocysteine is an independent risk factor for cardiovascular disease. However, the mechanisms are still unclear. Lectin-like oxidized LDL receptor-1 (LOX-1) has ligand specificity for oxidized LDL (oxLDL).

Patients with familial hypercholesterolaemia show enhanced spontaneous chemokine release from peripheral blood mononuclear cells ex vivo. Dependency of xanthomas/xanthelasms, smoking and gender.

Aims: Familial hypercholesterolaemia (FH) is associated with increased risk of premature atherosclerosis and coronary artery disease (CAD). However, onset of clinically manifested CAD varies widely among patients with heterozygous FH, and we hypothesized that inflammatory mediators such as chemokines could contribute to atherogenesis in these patients.

Methods And Results: We compared peripheral blood mononuclear cells (PBMCs) from FH patients with an identical mutation with PBMCs from sex- and age-matched healthy controls with respect to spontaneous and oxidized low density lipoprotein (oxLDL)-stimulated release of chemokines.

Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects.

Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia.

Background: Naturally occurring plant sterol esters (SEs) favorably affect serum cholesterol concentrations in humans and could aid in the treatment of children with familial hypercholesterolemia (FH).

Objective: We studied the effect of SE-enriched spread on serum lipids, lipoproteins, carotenoids, fat-soluble vitamins, and physiologic variables in children with FH aged 7-12 y.

Design: In a randomized, double-blind crossover study comprising two 8-wk interventions, 38 children with FH consumed 18.

Folic acid treatment reduces chemokine release from peripheral blood mononuclear cells in hyperhomocysteinemic subjects.

Elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia induces vascular disease are uncertain. An early step in atherogenesis involves leukocyte migration into the arterial wall, a process regulated in part by chemokines.