The Experts below are selected from a list of 4032 Experts worldwide ranked by ideXlab platform

Robert F Hoyt - One of the best experts on this subject based on the ideXlab platform.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine Koch
    Abstract:

    Abstract Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (−39% and −13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [3H]cholesteryl esters ([3H]CE) from HDL (fractional catabolic rate in days−1: LCAT-Tg = 3.7 ± 0.34, LCATxCETP-Tg = 6.1 ± 0.16, and controls = 6.4 ± 0.16) as well as the liver uptake of [3H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 ± 2.0 μm2 × 103) compared with LCAT-Tg mice (35.7 ± 2.0 μm2 × 103;p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [3H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine A Koch
    Abstract:

    Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

Bernhard Foger - One of the best experts on this subject based on the ideXlab platform.

  • adenoviral expression of human lecithin Cholesterol Acyltransferase in nonhuman primates leads to an antiatherogenic lipoprotein phenotype by increasing high density lipoprotein and lowering low density lipoprotein
    Metabolism-clinical and Experimental, 2009
    Co-Authors: Marcelo Amar, Robert D Shamburek, Catherine L Knapper, Bernhard Foger, Silvia Santamarinafojo, Hollis B Brewer, Alan T Remaley
    Abstract:

    Abstract Lecithin-Cholesterol Acyltransferase (LCAT), a key enzyme in high-density lipoprotein (HDL) metabolism, has been proposed to have atheroprotective properties by promoting reverse Cholesterol transport. Overexpression of LCAT in various animal models, however, has led to conflicting results on its overall effect on lipoproteins and atherosclerosis. In this study, the effect of overexpression of LCAT in nonhuman primates on lipoprotein metabolism is examined. Human LCAT was expressed with adenovirus in squirrel monkeys (n = 8), resulting on day 4 in a 22-fold increase of LCAT activity (257 ± 23 vs 5618 ± 799 nmol mL −1 h −1 , P P −1 , P −1 d −1 , P P −1 in controls vs 4.2 ± 0.3 d −1 in LCAT-treated group, P

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine Koch
    Abstract:

    Abstract Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (−39% and −13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [3H]cholesteryl esters ([3H]CE) from HDL (fractional catabolic rate in days−1: LCAT-Tg = 3.7 ± 0.34, LCATxCETP-Tg = 6.1 ± 0.16, and controls = 6.4 ± 0.16) as well as the liver uptake of [3H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 ± 2.0 μm2 × 103) compared with LCAT-Tg mice (35.7 ± 2.0 μm2 × 103;p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [3H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine A Koch
    Abstract:

    Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

Jamila Fruchartnajib - One of the best experts on this subject based on the ideXlab platform.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine Koch
    Abstract:

    Abstract Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (−39% and −13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [3H]cholesteryl esters ([3H]CE) from HDL (fractional catabolic rate in days−1: LCAT-Tg = 3.7 ± 0.34, LCATxCETP-Tg = 6.1 ± 0.16, and controls = 6.4 ± 0.16) as well as the liver uptake of [3H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 ± 2.0 μm2 × 103) compared with LCAT-Tg mice (35.7 ± 2.0 μm2 × 103;p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [3H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine A Koch
    Abstract:

    Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

Beverly Paigen - One of the best experts on this subject based on the ideXlab platform.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine Koch
    Abstract:

    Abstract Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (−39% and −13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [3H]cholesteryl esters ([3H]CE) from HDL (fractional catabolic rate in days−1: LCAT-Tg = 3.7 ± 0.34, LCATxCETP-Tg = 6.1 ± 0.16, and controls = 6.4 ± 0.16) as well as the liver uptake of [3H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 ± 2.0 μm2 × 103) compared with LCAT-Tg mice (35.7 ± 2.0 μm2 × 103;p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [3H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine A Koch
    Abstract:

    Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

Michael Chase - One of the best experts on this subject based on the ideXlab platform.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine Koch
    Abstract:

    Abstract Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (−39% and −13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [3H]cholesteryl esters ([3H]CE) from HDL (fractional catabolic rate in days−1: LCAT-Tg = 3.7 ± 0.34, LCATxCETP-Tg = 6.1 ± 0.16, and controls = 6.4 ± 0.16) as well as the liver uptake of [3H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 ± 2.0 μm2 × 103) compared with LCAT-Tg mice (35.7 ± 2.0 μm2 × 103;p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [3H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.

  • cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin Cholesterol Acyltransferase transgenic mice
    Journal of Biological Chemistry, 1999
    Co-Authors: Robert F Hoyt, Beverly Paigen, Boris Vaisman, Robert D Shamburek, Marcelo Amar, Bernhard Foger, Michael Chase, Jamila Fruchartnajib, Jorge Paiz, Christine A Koch
    Abstract:

    Expression of human lecithin Cholesterol Acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) Cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse Cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high Cholesterol diets, expression of CETP in LCAT-Tg mice reduced total Cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL Cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse Cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse Cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse Cholesterol transport.