Aims: Small dense LDL (sdLDL) cholesterol is considered a cardiovascular risk. Our purpose in this study was to evaluate the efficacy of rosuvastatin in reducing sdLDL and large buoyant LDL (lbLDL-C) in hypercholester...Aims: Small dense LDL (sdLDL) cholesterol is considered a cardiovascular risk. Our purpose in this study was to evaluate the efficacy of rosuvastatin in reducing sdLDL and large buoyant LDL (lbLDL-C) in hypercholesterolemia. Methods: Fifty-six patients with a mean baseline LDL-cholesterol (LDL-C) concentration of 173.9 ± 40.5 mg/dL were treated with rosuvastatin 2.5 mg/day for 12 weeks. LDL-C, sdLDL-C, and apolipoprotein (apo) B were assessed and l lbLDL-C was calculated (LDL-C minus sdLDL-C). Results: After 12-week treatment with rosuvastatin 2.5mg, sdLDL-C and lbLDL-C were significantly reduced from 62.1 ± 23.8 mg/dL to 34.0 ± 13.4 mg/dL, p <0.001 and 112.7 ± 34.9 mg/dL to 77.2± 29.2 mg/dL, p < 0.001 respectively, and sdLDL-C/lbLDL-C ratio and apo B also decreased significantly, from 0.36 ± 0.02 to 0.32 ± 0.02, p < 0.005 and 134.2 ± 4.3 to 93.6 ± 3.5 mg/dl, p < 0.001, respectively. In diabetic subjects there was significant correlation between percent reductions in the plasma triglyceride and sdLDL-C/ lbLDL-C ratio (r = 0.58, p < 0.005), but not between the percentage decrease in plasma triglyceride and sdLDL-C. Conclusions: Treatment with rosuvastatin is associated with significant reduction in sdLDL, lbLDL and sdLDL/lbLDL ratio.展开更多
Background: The atherogenic LDL is an impor-tant generative cause for the endothelial dys-function and the configuration of the athero-sclerotic lesions. CRP is a sensitive marker of inflammation on the vascular wall,...Background: The atherogenic LDL is an impor-tant generative cause for the endothelial dys-function and the configuration of the athero-sclerotic lesions. CRP is a sensitive marker of inflammation on the vascular wall, but also seems to participate in the atheromatic process. The correlation between LDL and CRP could form valuable guidelines for the initiation of a treatment with statins for individuals with an increased risk of ischemic incidents. Objectives: The aim of the study was to investigate a pos-sible correlation between LDL and CRP in an important number of apparently healthy indi-viduals. Methods: The study material consisted of the test results of 260 male and 484 female adults with normal LDL levels who were clini-cally healthy. The correlation between the LDL and the CRP values of this group was investi-gated in this group and CRP was compared with the respective values of a group of 60 male and 204 female adults with elevated LDL levels. Re-sults: It was ascertained that there is not a sta-tistically important correlation between LDL and CRP values in all groups (men, women, total) of the population with normal LDL levels. Addi-tionally, the CRP mean values were not statisti-cally different between the individuals with normal and raised LDL. Conclusion: A number of causes are incriminated for the results. More studies are definitely needed for the confirma-tion of the results, particularly if the findings could lead to the formation of guidelines for the application of a treatment in people with normal LDL levels but increased CRP levels.展开更多
Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotei...Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.展开更多
Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. ...Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.展开更多
Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocum...Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.展开更多
ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol...ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity. In the first experiment, 3 groups of 6 early-weaned piglets were fed low-fat diets containing either 1.5% CLA, 1.5% corn oil or 1.5% beef tallow;fat provided 8% of the energy intake. In the second experiment, 4 groups of 6 early-weaned piglets were fed high-fat di- ets containing either 15% beef tallow, 12% beef tal- low plus 3% CLA, 15% corn oil, or 12% corn oil plus 3% CLA; fat provided 29% of energy intake. Cholesterol was balanced across diets in both experi-ments. In pigs fed the low-fat diets, all dietary fats in- creased LDL-C and triacylglycerols and decreased high-density lipoprotein cholesterol ( HDL-C ) and very low-density lipoprotein cholesterol (VLDL-C). LDL-C was the same in pigs fed low-fat tallow or low-fat CLA diets. However, ACAT activity was near- ly 80% higher in pigs fed the low-fat tallow diet than in pigs fed the low-fat CLA diets. All high-fat diets increased LDL-C, HDL-C and triacylglycerols equally with no effect on VLDL-C. There were no unique fat- ty acid effects of the high-fat diets on ACAT activity. We conclude that supplemental fats had differential effects on hepatic ACAT activity and LDL-C, but on- ly in pigs fed low-fat diets.展开更多
Dysregulation of low-density lipoprotein(LDL)cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease.Endogenous molecules targeting LDL clearance play crucial roles...Dysregulation of low-density lipoprotein(LDL)cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease.Endogenous molecules targeting LDL clearance play crucial roles in the progression of liver steatosis.Human cathelicidin LL-37 can form complexes with lipoproteins,but whether these complexes regulate lipoprotein-driven cholesterol metabolism is not clear.Here,we find that cathelicidin LL-37 binds to LDL via apolipoprotein(Apo)B-100 domains,enhancing the solubility of Apo B-100 and inhibiting the modifications and aggregation of LDL.LL-37-LDL interaction promotes LDL uptake through LDL receptor(LDLR)both in hepatocytes and macrophages.This interaction also promotes LDL cholesterol clearance by facilitating cholesterol excretion and cholesterol efflux.In Apoe^(-/-)mice with hypercholesterolemia,the murine homolog cathelicidin Cramp similarly accelerates cholesterol clearance by activating cholesterol excretion and preventing hepatic lipid accumulation.This study identifies LL-37 as an endogenous regulator of LDL that promotes LDL cholesterol clearance.展开更多
文摘Aims: Small dense LDL (sdLDL) cholesterol is considered a cardiovascular risk. Our purpose in this study was to evaluate the efficacy of rosuvastatin in reducing sdLDL and large buoyant LDL (lbLDL-C) in hypercholesterolemia. Methods: Fifty-six patients with a mean baseline LDL-cholesterol (LDL-C) concentration of 173.9 ± 40.5 mg/dL were treated with rosuvastatin 2.5 mg/day for 12 weeks. LDL-C, sdLDL-C, and apolipoprotein (apo) B were assessed and l lbLDL-C was calculated (LDL-C minus sdLDL-C). Results: After 12-week treatment with rosuvastatin 2.5mg, sdLDL-C and lbLDL-C were significantly reduced from 62.1 ± 23.8 mg/dL to 34.0 ± 13.4 mg/dL, p <0.001 and 112.7 ± 34.9 mg/dL to 77.2± 29.2 mg/dL, p < 0.001 respectively, and sdLDL-C/lbLDL-C ratio and apo B also decreased significantly, from 0.36 ± 0.02 to 0.32 ± 0.02, p < 0.005 and 134.2 ± 4.3 to 93.6 ± 3.5 mg/dl, p < 0.001, respectively. In diabetic subjects there was significant correlation between percent reductions in the plasma triglyceride and sdLDL-C/ lbLDL-C ratio (r = 0.58, p < 0.005), but not between the percentage decrease in plasma triglyceride and sdLDL-C. Conclusions: Treatment with rosuvastatin is associated with significant reduction in sdLDL, lbLDL and sdLDL/lbLDL ratio.
文摘Background: The atherogenic LDL is an impor-tant generative cause for the endothelial dys-function and the configuration of the athero-sclerotic lesions. CRP is a sensitive marker of inflammation on the vascular wall, but also seems to participate in the atheromatic process. The correlation between LDL and CRP could form valuable guidelines for the initiation of a treatment with statins for individuals with an increased risk of ischemic incidents. Objectives: The aim of the study was to investigate a pos-sible correlation between LDL and CRP in an important number of apparently healthy indi-viduals. Methods: The study material consisted of the test results of 260 male and 484 female adults with normal LDL levels who were clini-cally healthy. The correlation between the LDL and the CRP values of this group was investi-gated in this group and CRP was compared with the respective values of a group of 60 male and 204 female adults with elevated LDL levels. Re-sults: It was ascertained that there is not a sta-tistically important correlation between LDL and CRP values in all groups (men, women, total) of the population with normal LDL levels. Addi-tionally, the CRP mean values were not statisti-cally different between the individuals with normal and raised LDL. Conclusion: A number of causes are incriminated for the results. More studies are definitely needed for the confirma-tion of the results, particularly if the findings could lead to the formation of guidelines for the application of a treatment in people with normal LDL levels but increased CRP levels.
文摘Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.
基金supported by the Ethics Committee of Sir Run Run Shaw Hospital of Zhejiang University [NO.20200224-33]Key Project of Medical and Health Science and Technology of Zhejiang Province [NO. WKJ-ZJ-1715]+7 种基金Zhejiang Province Traditional Chinese Medicine Science and Technology Project [NO. 2017ZA006]Natural Science Foundation of Zhejiang Province [NO. LQ17H020006]Medical health Science and Technology project of Zhejiang Province [NO. 2017KY207]National Natural Science Foundation of China [82070408]Medical and health project [2021RC014]Hangzhou Medical Health Science and Technology Project [B20200116]“Pioneer” and “Leading Goose” R&D Program of Zhejiang[2023C04013]Administration of Traditional Chinese Medicine of Zhejiang Province [GZY-ZJ-KJ-23001]。
文摘Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.
文摘Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.
基金Supported by USDA/CSREES Competitive Grant 98-35206-6286federal funds from the USDA,ARS under Cooperative Agreement no.58-6250-1-003
文摘ABSTRACT:Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ) can be decreased by conjugated linoleic acid (CLA) by depressing hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity. In the first experiment, 3 groups of 6 early-weaned piglets were fed low-fat diets containing either 1.5% CLA, 1.5% corn oil or 1.5% beef tallow;fat provided 8% of the energy intake. In the second experiment, 4 groups of 6 early-weaned piglets were fed high-fat di- ets containing either 15% beef tallow, 12% beef tal- low plus 3% CLA, 15% corn oil, or 12% corn oil plus 3% CLA; fat provided 29% of energy intake. Cholesterol was balanced across diets in both experi-ments. In pigs fed the low-fat diets, all dietary fats in- creased LDL-C and triacylglycerols and decreased high-density lipoprotein cholesterol ( HDL-C ) and very low-density lipoprotein cholesterol (VLDL-C). LDL-C was the same in pigs fed low-fat tallow or low-fat CLA diets. However, ACAT activity was near- ly 80% higher in pigs fed the low-fat tallow diet than in pigs fed the low-fat CLA diets. All high-fat diets increased LDL-C, HDL-C and triacylglycerols equally with no effect on VLDL-C. There were no unique fat- ty acid effects of the high-fat diets on ACAT activity. We conclude that supplemental fats had differential effects on hepatic ACAT activity and LDL-C, but on- ly in pigs fed low-fat diets.
基金supported by the National Key Research and Development Program of China(2022YFC2105003)the National Natural Science Foundation of China(92469103,31930015,32002311,U2002219)+8 种基金Chinese Academy of Sciences(SAJC202402)Yunnan Provincial Science and Technology Department(202001AT070128,202302AA310035,202003AD150008,202305AH340007)Chongqing Municipal Education Commission(HZ2021020)Kunming Science and Technology Bureau(2022SCP007)Shenzhen New Cornerstone Science Foundation(NCI202238)Yunnan Characteristic Plant Extraction Laboratory(2025YKZY002)Tianfu Jincheng Laboratory Foundation(TFJC2023010007)Key Laboratory of Cardiovascular Disease of Yunnan Province(2018DG008)Canadian Institutes of Health Research Foundation(389035)。
文摘Dysregulation of low-density lipoprotein(LDL)cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease.Endogenous molecules targeting LDL clearance play crucial roles in the progression of liver steatosis.Human cathelicidin LL-37 can form complexes with lipoproteins,but whether these complexes regulate lipoprotein-driven cholesterol metabolism is not clear.Here,we find that cathelicidin LL-37 binds to LDL via apolipoprotein(Apo)B-100 domains,enhancing the solubility of Apo B-100 and inhibiting the modifications and aggregation of LDL.LL-37-LDL interaction promotes LDL uptake through LDL receptor(LDLR)both in hepatocytes and macrophages.This interaction also promotes LDL cholesterol clearance by facilitating cholesterol excretion and cholesterol efflux.In Apoe^(-/-)mice with hypercholesterolemia,the murine homolog cathelicidin Cramp similarly accelerates cholesterol clearance by activating cholesterol excretion and preventing hepatic lipid accumulation.This study identifies LL-37 as an endogenous regulator of LDL that promotes LDL cholesterol clearance.