Biomedical subjects

Beverly Paigen

Publications and source records attributed to Beverly Paigen.

57 records · Page 4Linked to original sources

PubMed2001

The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice.

Identification of mutations in the ABCA1 transporter (ABCA1) as the genetic defect in Tangier disease has generated interest in modulating atherogenic risk by enhancing ABCA1 gene expression. To investigate the role of ABCA1 in atherogenesis, we analyzed diet-induced atherosclerosis in transgenic mice overexpressing human ABCA1 (hABCA1-Tg) and spontaneous lesion formation in hABCA1-Tg x apoE-knockout (KO) mice. Overexpression of hABCA1 in C57BL/6 mice resulted in a unique anti-atherogenic profile characterized by decreased plasma cholesterol (63%), cholesteryl ester (63%), free cholesterol (67%), non-high density lipoprotein (HDL)-cholesterol (53%), and apolipoprotein (apo) B (64%) but markedly increased HDL-cholesterol (2.8-fold), apoA-I (2.2-fold), and apoE (2.8-fold) levels. These beneficial changes in the lipid profile led to significantly lower (65%) aortic atherosclerosis in hABCA1-Tg mice. In marked contrast, ABCA1 overexpression had a minimal effect on the plasma lipid profile of apoE-KO mice and resulted in a 2- to 2.6-fold increase in aortic lesion area. These combined results indicate that overexpression of ABCA1 in C57BL/6 mice on a high cholesterol diet results in an atheroprotective lipoprotein profile and decreased atherosclerosis, and thus provide previously undocumented in vivo evidence of an anti-atherogenic role for the ABCA1 transporter. In contrast, overexpression of ABCA1 in an apoE-KO background led to increased atherosclerosis, further substantiating the important role of apoE in macrophage cholesterol metabolism and atherogenesis. In summary, these results establish that, in the presence of apoE, overexpression of ABCA1 modulates HDL as well as apoB-containing lipoprotein metabolism and reduces atherosclerosis in vivo, and indicate that pharmacological agents that will increase ABCA1 expression may reduce atherogenic risk in humans.

ATP Binding Cassette Transporter 1↗

PubMed1998

Microenvironment in Ventilated Animal Cages with Differing Ventilation Rates, Mice Populations, and Frequency of Bedding Changes.

The purpose of the study was to assess the microenvironment in separately ventilated mouse cages at differing ventilation rates, mice populations, and frequency of bedding changes. We monitored intracage temperature, relative humidity, and concentrations of ammonia and carbon dioxide during 3 experiments. First, the effect of ventilation rate on the microenvironment of cages housing adult male mice was evaluated at 30, 40, 60, 80 and 100 air changes/h. For all ventilation rates tested, ammonia concentration was less than 3 ppm, carbon dioxide concentration ranged from 840 to 3,300 ppm, relative humidity ranged from 42 to 65%, and temperature ranged from 23.2 to 25.3 C. Second, we monitored cage microenvironment continually in experiments during which changing of bedding was delayed. Male mice were used in the experiment, and cages were ventilated (60 air changes/h). Cages were allowed to accumulate soiled material for 26 days, during which time ammonia concentration and relative humidity did not exceed 10 ppm and 45%, respectively. Third, we tested ventilation rate and frequency of bedding changes in ventilated cages containing breeding trios (2 females, 1 male) and their pups. Ammonia concentrations remained at 25 ppm or less for 30, 60, and 100 air changes/h when bedding was changed weekly and for 100 air changes/h when bedding was changed every 2 weeks. We concluded that 30 air changes/h was sufficient to maintain a healthful microenvironment in cages that were housing adult male mice in which bedding was changed weekly. When frequency of bedding changes was reduced to every 2 weeks, 60 air changes/h was sufficient for cages housing adult males, but 100 air changes/h was necessary for cages housing breeding trios and pups.

Journal Article↗

PubMed1997

Impact of Room Ventilation Rates on Mouse Cage Ventilation and Microenvironment.

To assess the impact of room ventilation on animal cage microenvironment, intracage ventilation rate, temperature, humidity, and concentrations of carbon dioxide and ammonia were monitored in nonpressurized, bonnet-topped mouse cages. Cages on the top, middle, and bottom rows of a mouse rack were monitored at room ventilation rates of 0, 5, 10, and 20 air changes/h (ACH). Ventilation inside the animal cage increased somewhat from 12.8 to 18.9 ACH as room ventilation rate in- creased from 0 to 20 ACH, but the differences were not statistically significant, and most of the increase occurred in cages in the top row nearest to the fresh air supply. Cages containing mice had ventilation rate between 10 and 15 ACH even when room ventilation was reduced to 0 ACH; this ventilation is a result of the thermal heat load of the mice. After 6 days of soiled bedding, intracage ammonia concentration was c 3 ppm at all room ventilation rates and was not affected by increasing room ventilation. Temperature inside cages did not change with increasing ventilation. Humidity inside cages significantly decreased with increasing ventilation, from 55% relative humidity at 5 ACH to 36% relative humidity at 20 ACH. Carbon dioxide concentration decreased from 2,500 ppm to 1,900 ppm when ventilation rate increased from 5 ACH to 10 ACH, but no further significant decrease was observed at 20 ACH. In conclusion, increasing the room ventilation rate higher than 5 ACH did not result in significant improvements in the cage microenvironment.

Journal Article↗