Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

OBJECTIVE: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). APPROACH AND RESULTS: Arterial wall inflammation and bone marrow activity were measured using 18F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; P<0.001). Monocytes from patients with FD showed increased lipid accumulation (lipid-positive monocytes: Patients with FD 92% [86-95], controls 76% [66-81], P=0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10-276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. CONCLUSIONS: Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD.

Lipid-associated rheumatologic syndromes.

Rheumatologic manifestations of hyperlipidemia and lipid-associated arthritis are rarely seen in the rheumatologist's office. On the other hand, a rheumatologist may be the clinician who identifies and initiates proper therapy for disorders related to hyperlipidemia when the musculoskeletal manifestations of these syndromes are recognized. In this article both the joint and tendon manifestations are reviewed, including the lesser known lipid liquid crystal form of arthritis. The relationship between gout and hyperuricemia is briefly discussed, as are the autoimmune manifestations of lipid-lowering therapy.

[Dyslipoproteinemia and monoclonal gammopathy: a case report]. / Disbetalipoproteinemia e gammopatia monoclonale: descrizione di un caso clinico.

Type III hyperlipidemia is a rare metabolic disorder characterized by elevated plasma concentrations of cholesterol and triglycerides. In subjects homozygous for the isoform E2 of apoprotein E, the disease becomes manifest when other factors that interfere with normal lipoprotein metabolism are present. Multiple myeloma has also been found to be associated with type III hyperlipidemia. We report a case with the typical manifestations of the disease (hyperlipidemia and palmar xanthoma) in whom the family history and blood analyses excluded pathologies potentially interfering with lipid metabolism. On electrophoresis of serum proteins, a monoclonal peak was detected. The patient was homozygous for the isoform E2 of the apoprotein E. Further blood analyses, bone marrow and roentgen examinations enabled the diagnosis of monoclonal gammopathy of undetermined origin. The association of type III hyperlipidemia with monoclonal gammopathy might be casual, although only the characterization of the antigenic determinants toward which the monoclonal antibodies are directed could be conclusive. The presence of several family members homozygous for the isoform E2, but without the clinical and biochemical characteristics of type III hyperlipidemia, and the poor response to diet and drug therapy suggest that gammopathy may play role in determining hyperlipidemia.

[Anti-kappa elastin antibody titer in the sera of patients with hyperlipoproteinemia type II, III and IV]. / Miano przeciwcial przeciwko kappa elastynie w surowicach chorych na hiperlipoproteinemie typu II, III i IV.

Titre of antibodies against elastin degradation product (kappa-elastin) was measured in patients with atherogenic types of hyperlipoproteinemia. The hemagglutination technique was used. A significant decrease in titres of the tested antibodies was found. It was the most prominent in IIa, III and IIb types of hyperlipoproteinemia and rather mild in IV type. The authors attempted to explain causes of antibodies titres decrease in tested patients and relate their results with those of other authors.