Phenotypic and Functional Signatures of Peripheral Blood and Spleen Compartments of Cynomolgus Macaques Infected With : Associations With Cardiac Histopathological Characteristics.

We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with , identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls.

Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease.

Background: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease.

Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease.

Background: Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species.

Correlation between presence of Trypanosoma cruzi DNA in heart tissue of baboons and cynomolgus monkeys, and lymphocytic myocarditis.

Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi.

Longitudinal analysis of short-term high-fat diet on endothelial senescence in baboons.

A high-fat diet is a major risk factor for atherosclerosis. We conducted a longitudinal investigation to determine whether vascular endothelial senescence is involved in the mechanism by which a high-fat diet promotes atherogenesis. We challenged 10 baboons (Papio sp.

Steatohepatitis in laboratory opossums exhibiting a high lipemic response to dietary cholesterol and fat.

Plasma VLDL and LDL cholesterol were markedly elevated (>40-fold) in high-responding opossums, but moderately elevated (6-fold) in low-responding opossums after they had consumed a high-cholesterol and high-fat diet for 24 wk. In both high- and low-responding opossums, plasma triglycerides were slightly elevated, threefold and twofold, respectively. Dietary challenge also induced fatty livers in high responders, but not in low responders.

Differential expression of intestinal genes in opossums with high and low responses to dietary cholesterol.

High and low responding opossums (Monodelphis domestica) differ in their plasma very low density lipoprotein and low density lipoprotein (VLDL+LDL) cholesterol concentrations when they consume a high cholesterol diet, which is due in part to absorption of a higher percentage of dietary cholesterol in high responders. We compared the expression of a set of genes that influence cholesterol absorption in high and low responders fed a basal or a high cholesterol and low fat (HCLF) diet. Up-regulation of the ABCG5, ABCG8, and IBABP genes by the HCLF diet in high and low responders may reduce cholesterol absorption to maintain cholesterol homeostasis.

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums.

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders.

Effect of ezetimibe on plasma cholesterol levels, cholesterol absorption, and secretion of biliary cholesterol in laboratory opossums with high and low responses to dietary cholesterol.

Partially inbred lines of laboratory opossums differ in plasma low-density lipoprotein cholesterol concentration and cholesterol absorption on a high-cholesterol diet. The aim of the present studies was to determine whether ezetimibe inhibits cholesterol absorption and eliminates the differences in plasma cholesterol and hepatic cholesterol metabolism between high and low responders on a high-cholesterol diet. Initially, we determined that the optimum dose of ezetimibe was 5 mg/(kg d) and treated 6 high- and 6 low-responding opossums with this dose (with equal numbers of controls) for 3 weeks while the opossums consumed a high-cholesterol and low-fat diet.

Differential expression of hepatic genes involved in cholesterol homeostasis in high- and low-responding strains of laboratory opossums.

Plasma very low-density lipoprotein and low-density lipoprotein (VLDL+LDL) cholesterol levels of 2 partially inbred strains of opossums (Monodelphis domestica) differ markedly when they are fed a high-cholesterol and low-fat (HCLF) diet. High-responding opossums exhibit a dramatic increase (>10-fold) in VLDL+LDL cholesterol, whereas low-responding opossums exhibit a minimal increase (<2-fold) in VLDL+LDL cholesterol. The genes responsible for the accumulation of high levels of plasma VLDL+LDL cholesterol in high-responding opossums have not yet been identified.

Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet.

Background: Endothelial dysfunction signals the initiation and progression of atherosclerosis. Elevated LDL-cholesterol concentrations have been suggested to induce endothelial dysfunction, but direct in vivo evidence for the relation is still lacking.

Objective: We examined the hypothesis that a high-cholesterol, high-fat (HCHF) diet can directly cause endothelial dysfunction in vivo.

Low-density lipoprotein apolipoprotein B production differs between laboratory opossums exhibiting high and low lipemic responses to dietary cholesterol and fat.

Two partially inbred strains of laboratory opossums exhibit extremely high or low levels of low-density lipoprotein (LDL) cholesterol concentrations, respectively, when challenged with a high-cholesterol and high-fat (HCHF) diet. The present studies were conducted to determine whether the catabolism or the production of LDL apolipoprotein B (apoB) is responsible for the variability in plasma LDL cholesterol and apoB concentrations. Iodinated LDL prepared from plasma of donor opossums consuming HCHF diet was injected into high- and low-responding recipients maintained on the HCHF diet.

Effect of dietary cholesterol with or without saturated fat on plasma lipoprotein cholesterol levels in the laboratory opossum (Monodelphis domestica) model for diet-induced hyperlipidaemia.

Laboratory opossums (Monodelphis domestica) show extreme genetic variability in their responsiveness to dietary lipids; a great proportion of the genetic variability in responsiveness is due to a single major gene. To determine whether the major gene for dietary response detected by genetic analysis in opossums is responsive to dietary cholesterol or dietary saturated fat, or a combination of both, we used males and females of susceptible and resistant lines of laboratory opossums that were 5 to 7 months old. The animals were challenged with three different experimental diets (high-cholesterol diets with or without high saturated fat from lard or coconut oil) and plasma lipoproteins were measured.

Cholesterol absorption and hepatic acyl-coenzyme A:cholesterol acyltransferase activity play major roles in lipemic response to dietary cholesterol and fat in laboratory opossums.

Partially inbred lines of laboratory opossums differ considerably in their low-density lipoprotein (LDL) cholesterol responses to dietary cholesterol and fat. Genetic analysis suggested that a single major gene is responsible for the variation in LDL cholesterol on the high cholesterol and high fat (HCHF) diet. We measured cholesterol absorption and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in intestine and liver to narrow the search for the major gene.

Two quantitative trait loci affect ACE activities in Mexican-Americans.

Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study.

Two loci affect angiotensin I-converting enzyme activity in baboons.

Serum LDL cholesterol (LDLC) concentrations and ACE activities are risk factors for the development of cardiovascular disease (CVD). However, the relationship between ACE and CVD susceptibility, and possible mechanisms of action, is controversial. With data on 622 pedigreed baboons, we used statistical genetic methods to determine the mode of inheritance of ACE activities and its relationship to LDLC on different diets.

High and low responding strains of laboratory opossums differ in sterol 27-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase activities on a high cholesterol diet.

Two partially inbred strains of laboratory opossums exhibit extremely high or low levels of VLDL+LDL cholesterol concentrations, respectively, when challenged with a high cholesterol and high fat diet. The present studies were conducted to determine whether the high and low responding strains differ in activities of important enzymes that have been shown to affect lipemic responsiveness to diet. We measured plasma 27-hydroxycholesterol and hepatic activities of 27-hydroxylase and 7alpha-hydroxylase in high and low responding opossums while consuming the basal diet and cholesterol-enriched diets.

Genetic determination of HDL variation and response to diet in baboons.

We fed 634 baboons three diets to assess the separate effects of increasing dietary fat and cholesterol intakes on three independent measures of HDL phenotype: concentrations of HDL cholesterol and apoAI, and size distributions of HDL cholesterol. Increasing dietary fat significantly increased concentrations of HDL cholesterol and apoAI (both, P<0.0001), but did not affect HDL particle sizes, whereas increasing dietary cholesterol increased HDL cholesterol (P<0.