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Albert K. Groen - One of the best experts on this subject based on the ideXlab platform.
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reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Radjesh J Bisoendial, Jan Albert Kuivenhoven, Erik S.g. Stroes, John J. P. Kastelein, Folkert Kuipers, Frans Stellaard, Kees G Hovingh, Albert K. GroenAbstract:BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
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the role of the abca1 transporter and cholesterol efflux in familial Hypoalphalipoproteinemia
Journal of Lipid Research, 2003Co-Authors: Kees G Hovingh, Radjesh J Bisoendial, John J. P. Kastelein, Michael R. Hayden, Michel J A Van Wijland, Alison J Brownlie, Albert K. GroenAbstract:Defects in the gene encoding for the ATP binding cassette (ABC) transporter A1 (ABCA1) were shown to be one of the genetic causes for familial Hypoalphalipoproteinemia (FHA). We investigated the role of ABCA1-mediated cholesterol efflux in Dutch subjects suffering from FHA. Eighty-eight subjects (mean HDL cholesterol levels 0.63 +/- 0.21 mmol/l) were enrolled. Fibroblasts were cultured and loaded with [3H]cholesterol. ABCA1 and non-ABCA1-mediated efflux was studied by using apolipoprotein A-I (apoA-I), HDL, and methyl-beta-cyclodextrin as acceptors. Efflux to apoA-I was decreased in four patients (4/88, 4.5%), and in all cases, a mutation in the ABCA1 gene was found. In the remaining 84 subjects, no correlation between efflux and apoA-I or HDL cholesterol was found. Efflux to both HDL and cyclodextrin, in contrast, did correlate with HDL cholesterol plasma levels (r = 0.34, P = 0.01; and r = 0.27, P = 0.008, respectively). The prevalence of defects in ABCA1-dependent cholesterol efflux in Dutch FHA patients is low. The significant correlation between plasma HDL cholesterol levels and methyl-beta-cyclodextrin-mediated efflux in the FHA patients with normal ABCA1 function suggests that non-ABCA1-mediated efflux might also be important for plasma HDL cholesterol levels in these individuals.
Karim El Harchaoui - One of the best experts on this subject based on the ideXlab platform.
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reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Radjesh J Bisoendial, Jan Albert Kuivenhoven, Erik S.g. Stroes, John J. P. Kastelein, Folkert Kuipers, Frans Stellaard, Kees G Hovingh, Albert K. GroenAbstract:BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
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Reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
2009Co-Authors: Karim El Harchaoui, Franssen Remco, Hovingh G. Kees, Bisoendial, Radjesh J., Stellaard Frans, Kuipers Folkert, Kastelein, John J. P., Kuivenhoven, Jan Albert, Stroes, Erik S. G., Groen, Albert K.Abstract:Background: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. Results: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9 +/- 6.3 mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0 +/- 2.4 mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r = 0.53; p = 0.01). Conclusions: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels. (c) 2009 Elsevier Ireland Ltd. All rights reserve
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Consequences of cholesteryl ester transfer protein inhibition in patients with familial Hypoalphalipoproteinemia.
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Radjesh J Bisoendial, Karim El Harchaoui, Jan Albert Kuivenhoven, John J. P. Kastelein, Sotirios Tsimikas, Aeilko E. Zwinderman, G. Kees Hovingh, Johannes H.m. Levels, Erik S.g. StroesAbstract:To the Editor: A large proportion of clinical events cannot be prevented during statin therapy, which calls for novel drug targets to further improve cardiovascular outcome. In particular, HDL-increasing strategies hold great promise. The impact of decreased HDL-C on cardiovascular disease (CVD)-related morbidity and mortality has been sharply delineated in individuals affected by familial Hypoalphalipoproteinemia (FHA).1 HDL exerts multiple antiatherogenic actions beyond its role in reverse cholesterol transport, comprising antiinflammatory, antioxidative, and direct vascular effects.2 Whereas current strategies to raise HDL-C are limited, novel CETP-inhibitors are capable of mediating significant HDL-C elevation.3,4 Therefore, we evaluated the effects of CETP inhibition on lipid metabolism and markers of oxidation in subjects with FHA. Subjects were recruited from a Dutch population-based study to identify genes that control HDL-C levels,1 meeting the following criteria: (1) plasma HDL-C level below 10th percentile for age and sex; (2) absence of secondary lipid disorders; and (3) high likelihood of inherited low HDL (defined as HDL-C below 10th percentile in at least one first-degree family member). Nineteen FHA patients (13 men and 6 women; mean±SD age: 42.9±13.9 years), all free of overt macrovascular disease, were enrolled in the study. In 9 of these subjects the underlying defect was defined: heterozygosity for an apolipoprotein A-I (L178P) mutation,1 whereas in the remainder this genetic defect was excluded. The study protocol was approved …
Radjesh J Bisoendial - One of the best experts on this subject based on the ideXlab platform.
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reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Radjesh J Bisoendial, Jan Albert Kuivenhoven, Erik S.g. Stroes, John J. P. Kastelein, Folkert Kuipers, Frans Stellaard, Kees G Hovingh, Albert K. GroenAbstract:BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
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Consequences of cholesteryl ester transfer protein inhibition in patients with familial Hypoalphalipoproteinemia.
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Radjesh J Bisoendial, Karim El Harchaoui, Jan Albert Kuivenhoven, John J. P. Kastelein, Sotirios Tsimikas, Aeilko E. Zwinderman, G. Kees Hovingh, Johannes H.m. Levels, Erik S.g. StroesAbstract:To the Editor: A large proportion of clinical events cannot be prevented during statin therapy, which calls for novel drug targets to further improve cardiovascular outcome. In particular, HDL-increasing strategies hold great promise. The impact of decreased HDL-C on cardiovascular disease (CVD)-related morbidity and mortality has been sharply delineated in individuals affected by familial Hypoalphalipoproteinemia (FHA).1 HDL exerts multiple antiatherogenic actions beyond its role in reverse cholesterol transport, comprising antiinflammatory, antioxidative, and direct vascular effects.2 Whereas current strategies to raise HDL-C are limited, novel CETP-inhibitors are capable of mediating significant HDL-C elevation.3,4 Therefore, we evaluated the effects of CETP inhibition on lipid metabolism and markers of oxidation in subjects with FHA. Subjects were recruited from a Dutch population-based study to identify genes that control HDL-C levels,1 meeting the following criteria: (1) plasma HDL-C level below 10th percentile for age and sex; (2) absence of secondary lipid disorders; and (3) high likelihood of inherited low HDL (defined as HDL-C below 10th percentile in at least one first-degree family member). Nineteen FHA patients (13 men and 6 women; mean±SD age: 42.9±13.9 years), all free of overt macrovascular disease, were enrolled in the study. In 9 of these subjects the underlying defect was defined: heterozygosity for an apolipoprotein A-I (L178P) mutation,1 whereas in the remainder this genetic defect was excluded. The study protocol was approved …
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restoration of endothelial function by increasing high density lipoprotein in subjects with isolated low high density lipoprotein
Circulation, 2003Co-Authors: Radjesh J Bisoendial, John J. P. Kastelein, Michael R. Hayden, Kees G Hovingh, Johannes H.m. Levels, Peter Lerch, Irmgard Andresen, Erik S.g. StroesAbstract:Background— Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial Hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial Hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL. Methods and Results— In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium-dependent and -independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthase NG-monomethyl-l-arginine (L-NMMA) were measured. Dose-response curves were repeated after systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.4±0.2 mmol/L; P<0.05), and their forearm blood flow responses to both 5HT (maximum, 49.0±10.4%) a...
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the role of the abca1 transporter and cholesterol efflux in familial Hypoalphalipoproteinemia
Journal of Lipid Research, 2003Co-Authors: Kees G Hovingh, Radjesh J Bisoendial, John J. P. Kastelein, Michael R. Hayden, Michel J A Van Wijland, Alison J Brownlie, Albert K. GroenAbstract:Defects in the gene encoding for the ATP binding cassette (ABC) transporter A1 (ABCA1) were shown to be one of the genetic causes for familial Hypoalphalipoproteinemia (FHA). We investigated the role of ABCA1-mediated cholesterol efflux in Dutch subjects suffering from FHA. Eighty-eight subjects (mean HDL cholesterol levels 0.63 +/- 0.21 mmol/l) were enrolled. Fibroblasts were cultured and loaded with [3H]cholesterol. ABCA1 and non-ABCA1-mediated efflux was studied by using apolipoprotein A-I (apoA-I), HDL, and methyl-beta-cyclodextrin as acceptors. Efflux to apoA-I was decreased in four patients (4/88, 4.5%), and in all cases, a mutation in the ABCA1 gene was found. In the remaining 84 subjects, no correlation between efflux and apoA-I or HDL cholesterol was found. Efflux to both HDL and cyclodextrin, in contrast, did correlate with HDL cholesterol plasma levels (r = 0.34, P = 0.01; and r = 0.27, P = 0.008, respectively). The prevalence of defects in ABCA1-dependent cholesterol efflux in Dutch FHA patients is low. The significant correlation between plasma HDL cholesterol levels and methyl-beta-cyclodextrin-mediated efflux in the FHA patients with normal ABCA1 function suggests that non-ABCA1-mediated efflux might also be important for plasma HDL cholesterol levels in these individuals.
Erik S.g. Stroes - One of the best experts on this subject based on the ideXlab platform.
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reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Radjesh J Bisoendial, Jan Albert Kuivenhoven, Erik S.g. Stroes, John J. P. Kastelein, Folkert Kuipers, Frans Stellaard, Kees G Hovingh, Albert K. GroenAbstract:BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
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Consequences of cholesteryl ester transfer protein inhibition in patients with familial Hypoalphalipoproteinemia.
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Radjesh J Bisoendial, Karim El Harchaoui, Jan Albert Kuivenhoven, John J. P. Kastelein, Sotirios Tsimikas, Aeilko E. Zwinderman, G. Kees Hovingh, Johannes H.m. Levels, Erik S.g. StroesAbstract:To the Editor: A large proportion of clinical events cannot be prevented during statin therapy, which calls for novel drug targets to further improve cardiovascular outcome. In particular, HDL-increasing strategies hold great promise. The impact of decreased HDL-C on cardiovascular disease (CVD)-related morbidity and mortality has been sharply delineated in individuals affected by familial Hypoalphalipoproteinemia (FHA).1 HDL exerts multiple antiatherogenic actions beyond its role in reverse cholesterol transport, comprising antiinflammatory, antioxidative, and direct vascular effects.2 Whereas current strategies to raise HDL-C are limited, novel CETP-inhibitors are capable of mediating significant HDL-C elevation.3,4 Therefore, we evaluated the effects of CETP inhibition on lipid metabolism and markers of oxidation in subjects with FHA. Subjects were recruited from a Dutch population-based study to identify genes that control HDL-C levels,1 meeting the following criteria: (1) plasma HDL-C level below 10th percentile for age and sex; (2) absence of secondary lipid disorders; and (3) high likelihood of inherited low HDL (defined as HDL-C below 10th percentile in at least one first-degree family member). Nineteen FHA patients (13 men and 6 women; mean±SD age: 42.9±13.9 years), all free of overt macrovascular disease, were enrolled in the study. In 9 of these subjects the underlying defect was defined: heterozygosity for an apolipoprotein A-I (L178P) mutation,1 whereas in the remainder this genetic defect was excluded. The study protocol was approved …
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restoration of endothelial function by increasing high density lipoprotein in subjects with isolated low high density lipoprotein
Circulation, 2003Co-Authors: Radjesh J Bisoendial, John J. P. Kastelein, Michael R. Hayden, Kees G Hovingh, Johannes H.m. Levels, Peter Lerch, Irmgard Andresen, Erik S.g. StroesAbstract:Background— Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial Hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial Hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL. Methods and Results— In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium-dependent and -independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthase NG-monomethyl-l-arginine (L-NMMA) were measured. Dose-response curves were repeated after systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.4±0.2 mmol/L; P<0.05), and their forearm blood flow responses to both 5HT (maximum, 49.0±10.4%) a...
John J. P. Kastelein - One of the best experts on this subject based on the ideXlab platform.
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Restoration of Endothelial Function by Increasing High-Density Lipoprotein in Subjects With Isolated Low
2015Co-Authors: High-density Lipoprotein, John J. P. KasteleinAbstract:Background—Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial Hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial hypoalphalipopro-teinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL. Methods and Results—In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium-dependent and-independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (L-NMMA) were measured. Dose-response curves were repeated after systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.40.2 mmol/L; P0.05), and their forearm blood flow responses to both 5HT (maximum, 49.010.4%) and L-NMMA (maximum, 22.822.9%) were blunted compared with control subjects (both P0.005). Infusion of apoA-I/PC disks increased plasma HDL to 1.30.4 mmol/L in ABCA1 heterozygotes, which resulted in complete restoration of vasomotor responses to both 5HT and L-NMMA (both P0.001). Endothelium-independent vasodilation remained unaltered throughout the protocol. Conclusions—In ABCA1 heterozygotes, isolated low HDL is associated with endothelial dysfunction, attested to b
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reduced fecal sterol excretion in subjects with familial Hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Radjesh J Bisoendial, Jan Albert Kuivenhoven, Erik S.g. Stroes, John J. P. Kastelein, Folkert Kuipers, Frans Stellaard, Kees G Hovingh, Albert K. GroenAbstract:BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal sterol excretion was studied in 12 subjects with familial Hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral sterol excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral sterol excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal sterol excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
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Consequences of cholesteryl ester transfer protein inhibition in patients with familial Hypoalphalipoproteinemia.
Arteriosclerosis thrombosis and vascular biology, 2005Co-Authors: Radjesh J Bisoendial, Karim El Harchaoui, Jan Albert Kuivenhoven, John J. P. Kastelein, Sotirios Tsimikas, Aeilko E. Zwinderman, G. Kees Hovingh, Johannes H.m. Levels, Erik S.g. StroesAbstract:To the Editor: A large proportion of clinical events cannot be prevented during statin therapy, which calls for novel drug targets to further improve cardiovascular outcome. In particular, HDL-increasing strategies hold great promise. The impact of decreased HDL-C on cardiovascular disease (CVD)-related morbidity and mortality has been sharply delineated in individuals affected by familial Hypoalphalipoproteinemia (FHA).1 HDL exerts multiple antiatherogenic actions beyond its role in reverse cholesterol transport, comprising antiinflammatory, antioxidative, and direct vascular effects.2 Whereas current strategies to raise HDL-C are limited, novel CETP-inhibitors are capable of mediating significant HDL-C elevation.3,4 Therefore, we evaluated the effects of CETP inhibition on lipid metabolism and markers of oxidation in subjects with FHA. Subjects were recruited from a Dutch population-based study to identify genes that control HDL-C levels,1 meeting the following criteria: (1) plasma HDL-C level below 10th percentile for age and sex; (2) absence of secondary lipid disorders; and (3) high likelihood of inherited low HDL (defined as HDL-C below 10th percentile in at least one first-degree family member). Nineteen FHA patients (13 men and 6 women; mean±SD age: 42.9±13.9 years), all free of overt macrovascular disease, were enrolled in the study. In 9 of these subjects the underlying defect was defined: heterozygosity for an apolipoprotein A-I (L178P) mutation,1 whereas in the remainder this genetic defect was excluded. The study protocol was approved …
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efflux and atherosclerosis the clinical and biochemical impact of variations in the abca1 gene
Arteriosclerosis Thrombosis and Vascular Biology, 2003Co-Authors: Roshni R. Singaraja, John J. P. Kastelein, Henk Visscher, Liam R. Brunham, Michael R. HaydenAbstract:Approximately 50 mutations and many single nucleotide polymorphisms have been described in the ABCA1 gene, with mutations leading to Tangier disease and familial Hypoalphalipoproteinemia. Homozygotes and heterozygotes for mutations in ABCA1 display a wide range of phenotypes. Identification of ABCA1 as the molecular defect in these diseases has allowed for ascertainment based on genetic status and determination of genotype-phenotype correlations and has permitted us to identify mutations conferring a range of severity of cellular, biochemical, and clinical phenotypes. In this study we review how genetic variation at the ABCA1 locus affects its role in the maintenance of lipid homeostasis and the natural progression of atherosclerosis.
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restoration of endothelial function by increasing high density lipoprotein in subjects with isolated low high density lipoprotein
Circulation, 2003Co-Authors: Radjesh J Bisoendial, John J. P. Kastelein, Michael R. Hayden, Kees G Hovingh, Johannes H.m. Levels, Peter Lerch, Irmgard Andresen, Erik S.g. StroesAbstract:Background— Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial Hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial Hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL. Methods and Results— In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium-dependent and -independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthase NG-monomethyl-l-arginine (L-NMMA) were measured. Dose-response curves were repeated after systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.4±0.2 mmol/L; P<0.05), and their forearm blood flow responses to both 5HT (maximum, 49.0±10.4%) a...