Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents Development and Progression of Atherosclerosis in New Zealand White Rabbits.

BACKGROUND: Inflammatory immune response to atherogenic self-antigens plays an important role in the development of atherosclerosis. We evaluated the role of oral tolerance to three peptides in controlling atherosclerosis in New Zealand white rabbits. METHODS: Peptides derived from apolipoprotein B (ApoB), heat shock protein 60, and outer membrane protein from Chlamydia pneumoniae were expressed as part of the dendroaspin protein scaffold (AHC). Groups of 3-month-old rabbits were dosed orally with purified AHC protein either before the onset of disease or 2 months after inducing atherosclerosis; they were euthanized at the age of 7 months to study disease development and progression. RESULTS: Oral treatment with AHC resulted in a marked increase in regulatory T cells in the lymphoid organs and reduced the development and progression of atherosclerosis by 48.6% and 28.4%, respectively (P < 0.05). Oral tolerance decreased plaque inflammation, enhanced expression of anti-inflammatory and regulatory markers in the aorta, and attenuated the adaptive immune response to self-antigens. AHC treatment in rabbits with established disease significantly decreased vascular cell adhesion molecule 1 (VCAM-1) (6.2 fold) and monocyte chemoattractant protein-1(MCP-1) (3 fold) expression and reduced the infiltration of macrophages into the aorta. Collagen content and the smooth muscle cell-to-macrophage ratio were higher in treated animals, whereas markers of plaque vulnerability, including matrix metalloproteinase expression, were reduced. CONCLUSIONS: Our results suggest that oral tolerance to multiantigenic AHC molecule restores the immune balance and induces markers of plaque stability in rabbits.

[Recent development of natural and reconstituted lipoprotein based nano drug delivery vehicles].

Lipoproteins are biological lipids carriers. The natural and reconstituted lipoprotein based drug delivery systems have been extensively developed in recent years. This article reviews the development of natural and reconstituted low-density lipoprotein and high-density lipoprotein based vehicles in the antitumor area.

Peripheral delivery of a CNS targeted, metalo-protease reduces aß toxicity in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid ß-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aß, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.

Long-term effects of participation in a randomized trial of a low-fat, high-carbohydrate diet.

In 1982 we started a series of pilot studies to examine the feasibility of dietary intervention with a low-fat, high-carbohydrate diet in women with extensive mammographic densities. The purpose of the present paper is to examine the long-term effects of participation in these studies by assessing nutrient intake and other variables several years after active participation had stopped. Two hundred sixteen women were eligible for the follow-up study and were invited to attend and interview with a dietician. Data were collected by food frequency questionnaire from 157 subjects (73%), and blood was obtained from 115 subjects. Total energy intake was slightly lower in the intervention group. Total fat and percent energy from fat were significantly lower in the intervention group. The intake of all types of fat (saturated fat, linoleic acid, and oleic acid) and dietary cholesterol was lower in the in the intervention group; however, the polyunsaturated/saturated fat ratio did not differ between the groups. Total cholesterol and apoprotein B levels were lower in the intervention group compared to the control group. Follicle-stimulating hormone was 29% higher in postmenopausal members of the intervention group than in controls, but there was no difference in levels of estradiol. A total of 19 women enrolled in pilot studies had developed breast cancer, 5.7 times the number expected, confirming that the selection of women with extensive mammographic densities does identify a high-risk group. These data suggest that even quite short periods of intensive dietary counselling may have prolonged effects on diet, and that once subjects have adopted new dietary habits, the habits may persist even in the absence of continued counselling.