Israel Medical Association Journal

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

An arginine-rich apolipoprotein was discovered 50 years ago and became known as apolipoprotein E (ApoE) 10 years later. ApoE is associated with triglyceride-rich lipoproteins and mediates the clearance of these lipoproteins from the plasma. The ApoE-deficient hypercholesterolemic mice are an excellent platform for experimental atherosclerosis because they are similar to human pathology with regard to an atherogenic diet. ApoE is mainly produced in the liver and central nervous system cells. Three alleles determine six ApoE phenotypes with different metabolic effects and plasma cholesterol levels. Type III dysbetalipoproteinemia is associated with wide-spread atherogenesis with a defective ApoE2 resulting in delayed clearance of triglyceride-rich lipoproteins. ApoE4 substantially increases the risk including age of onset, progression, and prognosis of Alzheimer’s disease. Therefore, much effort has been directed to the elucidation of the pathogenic role of ApoE related to amyloid β (Aβ) acquisition in the brain. The ApoE trail passing from an enigmatic protein to a major player in cardiovascular and neurodegenerative disorders is reviewed

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.