Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP

Chapman, M. John; Orsoni, Alexina; Robillard, Paul; Thérond, Patrice; Giral, Philippe

doi:10.1016/j.jacl.2018.02.001

Cited by 13 publications

(44 citation statements)

References 76 publications

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“…Statins, known to lower cholesterol and LDLc levels, possess other effects, such as endothelial function improvement and antioxidant and anti-inflammatory properties. According to the literature, the effects of statin on HDL subfractions are especially related with subfraction composition [42–44]; concerning the effect of statins on the size of LDL subfractions, data is controversial [42, 45]. Nonetheless, in our study, the number of diabetic, overweight, and obese patients on statin therapy was higher than in the other groups analyzed.…”

Section: Discussioncontrasting

confidence: 48%

The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index

Coimbra

Reis

Nunes

et al. 2019

Oxidative Medicine and Cellular Longevity

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Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM (n=17) and with DM+HT (n=70), as compared to patients without DM or HT (n=69) or only with HT (n=38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients (n=45), as compared to normoponderal patients (n=81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.

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Section: Discussioncontrasting

confidence: 48%

The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index

Coimbra

Reis

Nunes

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Thus, it was implied that CETP variants may not contribute to the statin action to increase LDL receptor activity in our patients. Chapman et al 19 indicated that statins not only reduced the elevated levels of atherogenic apoB-containing lipoproteins by lipolysis and hepatic removal by increasing LDL receptor activity but also attenuated CETP activity after decreased CETP expression. Although statin treatment reduces CETP activity by up to 30%, considerable interindividual variation is observed 39,40 partly due to genetic variants within CETP.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17] The interaction between CETP and response to statin therapy may be relevant to mixed dyslipidemia. 18,19 CETP activity has a strong genetic component, and CETP gene variants can contribute to ASCVD risk. [20][21][22][23] Numerous studies have investigated the association between CETP polymorphisms and metabolic abnormalities such as obesity, hypertension, and insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Association of CETP Gene Variants with Atherogenic Dyslipidemia Among Thai Patients Treated with Statin

Srisawasdi¹,

Rodcharoen²,

Vanavanan³

et al. 2021

PGPM

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“…Recent evidence demonstrated a slight increase in CETP activity with long-term pitavastatin treatment [47]. In addition, fenofibrate treatment upregulates the expression of CETP [48].…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits

Flores-Castillo

Luna-Luna

Carreón‐Torres

et al. 2019

IJMS

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Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography–mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs.

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Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP

Cited by 13 publications

References 76 publications

The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index

The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index

Association of CETP Gene Variants with Atherogenic Dyslipidemia Among Thai Patients Treated with Statin

Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits

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