Hyperbaric oxygen treatment attenuates the pro-inflammatory and immune responses in apolipoprotein E knockout mice.

Chronic hyperbaric oxygen (HBO) therapy significantly attenuates atherosclerosis in New Zealand white rabbits as well as the apoE knockout (KO) mice, independent of plasma lipid concentrations and lipoprotein profiles. Because atherosclerosis has many features of a chronic inflammatory disease, in which both cell-mediated and humoral immune responses participate, we examined the effect of HBO treatment on various aspects of the immune response. We now demonstrate that in apoE KO mice, HBO treatment significantly reduces the circulating levels of antibodies to (MDA)LDL, both in the IgG and IgM class, as well as the delayed-type hypersensitivity (DTH) response to oxLDL challenge. Furthermore, HBO treatment results in a profound attenuation in the production of pro-inflammatory cytokines in response to an inflammatory stimulus (LPS), which is accompanied by a marked increase in the constitutive production of the anti-inflammatory cytokine IL-10 by spleen cells, independent of antigen specificity, as indicated by polyclonal activation of T cells. Our results demonstrate that HBO treatment results in the dampening of T and B cell-mediated responses to oxLDL or inflammatory stimuli.

Chronic hyperbaric oxygen treatment elicits an anti-oxidant response and attenuates atherosclerosis in apoE knockout mice.

We previously demonstrated that hyperbaric oxygen (HBO) treatment inhibits diet-induced atherosclerosis in New Zealand White rabbits. In the present study we investigate the mechanisms that might be involved in the athero-protective effect of HBO treatment in a well-accepted model of atherosclerosis, the apoE knockout (KO) mouse. We examine the effects of daily HBO treatment (for 5 and 10 weeks) on the components of the anti-oxidant defense mechanism and the redox state in blood, liver and aortic tissues and compare them to those of untreated apoE KO mice. HBO treatment results in a significant reduction of aortic cholesterol content and decreased fatty streak formation. These changes are accompanied by a significant reduction of autoantibodies against oxidatively modified LDL and profound changes in the redox state of the liver and aortic tissues. A 10-week treatment significantly reduces hepatic levels of TBARS and oxidized glutathione, while significantly increases the levels of reduced glutathione, glutathione reductase (GR), transferase, Se-dependent glutathione peroxidase and catalase (CAT). The effects of HBO treatment are similar in the aortic tissues. These observations provide evidence that HBO treatment has a powerful effect on the redox state of relevant tissues and produces an environment that inhibits oxidation. The anti-oxidant response may be the key to the anti-atherogenic effect of HBO treatment.

Cardiovascular risk factors in Mexican-American children at risk for type 2 diabetes mellitus (T2DM).

PURPOSE: To assess risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) with the hypothesis that risk for T2DM in children would be associated with an increase in risk factors for CVD. METHODS: Subjects from a group of Mexican-American school children (aged 10-12 years) identified to be at risk for T2DM, and their siblings, were selected for this study. There were 68 children with acanthosis nigricans (AN+), and 71 without AN (AN-). Both AN+ and AN- children were assessed for T2DM and CVD risk factors. Probands and siblings were evaluated by physical examination, family history, and fasting serum parameters: glucose, insulin, body mass index (BMI), serum lipoproteins, and oxidized lipids. Data were analyzed by descriptive, univariate, and multivariate procedures. RESULTS: BMI, waist/hip ratio, systolic and diastolic blood pressure were all significantly higher (p <.002) in AN+, whereas Tanner stages were similar in both groups. Fasting serum glucose was in the normal range, whereas insulin was elevated in AN+ compared with AN- (30.0 +/- 1.9 microU/mL vs. 14.8 +/- 1.0 p <.0001). Insulin resistance as assessed by the homeostasis assessment model (HOMA-IR) was elevated in both groups, although higher among AN+ (p <.0001). High-density lipoprotein-cholesterol (HDL-C) was lower (6.2 mg/dL) in the AN+ group (p <.003). The lower HDL-C in AN+ was associated with elevated triglycerides and a higher serum total cholesterol TC/HDL-C ratio when contrasted with the AN- values (145.9 +/- 7.6 mg/dL vs. 97.1 +/- 0.07, p <.0001; 4.1 +/- 0.2 vs. 3.4 +/- 0.1, p <.0001, respectively). In addition to the high prevalence of overweight/obesity (BMI > 85th percentile) in this population (76.3%, 106/139), elevated insulin (59.7% >15 microU/mL), low HDL-C (27.3% <40 mg/dL), and elevated low-density lipoprotein cholesterol (LDL-C) (41.0% >100 mg/dL) were also detected. CONCLUSIONS: The altered metabolic pattern observed in this group of Mexican-American children is characteristic of metabolic syndrome, a condition associated with obesity and increased risk for both T2DM and CVD in adults. This study points to the value of BMI and acanthosis nigricans as easily accessible markers for children and nuclear families at increased risk for developing T2DM and CVD.

Dietary fats differentially modulate the expression of lecithin:cholesterol acyltransferase, apoprotein-A1 and scavenger receptor b1 in rats.

In the present study the effects of dietary fat with defined fatty acids on lecithin:cholesterol acyltransferase (LCAT) and apoA-1, the two components of HDL that play a major role in reverse cholesterol transport (RCT), were examined. In addition, the expression of scavenger receptor B1 (SR-B1), the receptor involved in the uptake of HDL core lipids, was also determined under the same conditions in rats fed semisynthetic diets supplemented with triolein (TO), tripalmitin (TP) or menhaden oil (MO). Serum LCAT activity [ micro mol CE/(L.h)] was significantly (P < 0.05) higher in rats fed TO (33 +/- 4) compared with those fed TP (23 +/- 3) or MO (21 +/- 1). The levels of hepatic LCAT mRNA and hepatic SR-B1 receptor protein did not differ between rats fed TP and MO. The triolein diet, on the other hand, increased the induction of hepatic LCAT mRNA and hepatic SR-B1 receptor protein 1.5- to 2-fold. Serum HDL cholesterol concentrations differed among all groups and were 1.30 +/- 0.08, 1.17 +/- 0.10 and 0.91 +/- 0.06 mmol/L for TO-, TP- and MO-fed rats, respectively. Serum apoA-1 levels were significantly higher in TO-fed rats than in the other two groups. The data indicate that TO increases the secretion of HDL and its components (apoA-1 and LCAT), and stimulates the production of hepatic SR-B1 receptor protein. Overall, these results suggest that triolein may promote RCT and thus retard the development of atherosclerosis.