Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

The cellular composition of atherosclerotic lesions is determined by many factors including cell infiltration, proliferation and cell death. Tumor suppressor gene p53 has been shown to regulate both cell proliferation and cell death in many cell types. In the present study, we investigated the role of macrophage p53 in the pathogenesis of early...

Macrophage-specific inhibition of NF-κB activation reduces foam-cell formation

Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor κB (NF-κB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-κB activation is specifically inhibited in macrophages by overexpressing...

Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification

Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...

Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice

The cellular composition of an atherosclerotic lesion is determined by cell infiltration, proliferation, and apoptosis. The tumor suppressor gene retinoblastoma (Rb) has been shown to regulate both cell proliferation and cell death in many cell types. To study the role of macrophage Rb in the development of atherosclerosis, we used apoE...

Acyl-CoA:Cholesterol acyltransferase inhibitor avasimibe reduces atherosclerosis in addition to its cholesterol-lowering effect in ApoE*3-leiden mice

Background - The present study investigated whether the ACAT inhibitor avasimibe can reduce atherogenesis independently of its cholesterol-lowering effect in ApoE*3-Leiden mice. Methods and Results - Two groups of 15 female ApoE*3-Leiden mice were put on a high-cholesterol (HC) diet; 1 group received 0.01% (wt/wt) avasimibe mixed into the diet....

Protection from obesity in mice lacking the VLDL receptor

It has previously been reported that mice lacking the VLDL receptor (VLDLR-/-) exhibit normal plasma lipid levels and a modest decrease in adipose tissue mass. In the present study, the effect of VLDLR deficiency on profound weight gain was studied in mice. Obesity was induced either by feeding of a high-fat, high-calorie (HFC) diet or by...

Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: An immunohistochemical study

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty...

Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3Leiden transgenic mice

Apolipoprotein (apo) E3Leiden is a dysfunctional apo E variant associated with familial dysbetalipoproteinemia in humans. Transgenic mice carrying the APOE3Leiden gene develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. An early step in atherosclerosis is foam cell formation, which is thought to result from the...

Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages

Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic mouse model expressing both isoforms of the...

Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1

Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum cholesterol and TG were due mainly to an...

Characterisation of a mouse model with chronic proliferative dermatitis (cpdm/cpdm)

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum...

A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and tail are not involved. The lesions are...

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase...

Flow cytometric DNA measurement and cytomorphometric analysis of formalin fixed rat mammary tumours

Archival paraffin embedded material was used to examine whether additional quantitative criteria would be helpful to discriminate between histologically benign and malignant rat mammary tumours. To this end nuclear DNA content expressed as DNA ploidy index (DI) was measured using flow cytometry (FCM). A total of 63 benign and malignant mammary...