RESUMEN
BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
Asunto(s)
Antioxidantes/farmacología , Apolipoproteína B-48/efectos de los fármacos , Ácido Ascórbico/farmacología , Hiperlipidemias/prevención & control , Lipoproteínas HDL/efectos de los fármacos , Isquemia Miocárdica/prevención & control , Vitamina E/farmacología , Animales , Apolipoproteína B-48/sangre , Cardiotónicos/farmacología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/prevención & control , Citocinas/sangre , Dieta Aterogénica , Suplementos Dietéticos , Ensayo de Inmunoadsorción Enzimática , Femenino , Hiperlipidemias/sangre , Immunoblotting , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas HDL/sangre , Masculino , Ratones Endogámicos C57BL , Isquemia Miocárdica/sangre , Proteínas de Transferencia de Fosfolípidos/sangre , Valores de Referencia , Reproducibilidad de los Resultados , Receptores Depuradores de Clase B/sangre , Receptores Depuradores de Clase B/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
Asunto(s)
Animales , Masculino , Femenino , Ácido Ascórbico/farmacología , Vitamina E/farmacología , Isquemia Miocárdica/prevención & control , Apolipoproteína B-48/efectos de los fármacos , Hiperlipidemias/prevención & control , Lipoproteínas HDL/efectos de los fármacos , Antioxidantes/farmacología , Valores de Referencia , Enfermedad de la Arteria Coronaria/prevención & control , Enfermedad de la Arteria Coronaria/sangre , Ensayo de Inmunoadsorción Enzimática , Cardiotónicos/farmacología , Immunoblotting , Reproducibilidad de los Resultados , Citocinas/sangre , Resultado del Tratamiento , Isquemia Miocárdica/sangre , Suplementos Dietéticos , Proteínas de Transferencia de Fosfolípidos/sangre , Dieta Aterogénica , Receptores Depuradores de Clase B/efectos de los fármacos , Receptores Depuradores de Clase B/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Apolipoproteína B-48/sangre , Hiperlipidemias/sangre , Lipoproteínas HDL/sangre , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: Scavenger receptor class BI (SR-BI), authentic high-density lipoprotein (HDL) receptors expressed in liver, are known to play an important role in HDL-cholesterol (C) metabolism and reverse cholesterol transport. Interestingly, obese rats of WNIN/Ob strain have abnormally elevated levels of serum HDL-C compared with their lean counterparts. Based on the well-established role of SR-B1 in HDL-C metabolism, it was hypothesized that these obese rats may have an underexpression of hepatic SR-B1 receptors. In view of the significant role of vitamin A in energy expenditure and obesity, we also tested whether vitamin A supplementation can correct abnormal HDL-C metabolism. RESEARCH METHODS AND PROCEDURES: To test this hypothesis, 7-month-old male lean and obese rats of WNIN/Ob strain were divided into two groups; each group was subdivided into two subgroups consisting of six lean and six obese rats and received diets containing either 2.6 or 129 mg vitamin A/kg diet for 2 months. RESULTS: At the end, obese rats receiving normal levels of vitamin A diet showed high serum HDL-C and lower hepatic SR-BI expression levels compared with lean counterparts. Furthermore, chronic dietary vitamin A supplementation resulted in overexpression of hepatic SR-BI receptors (protein and gene) with concomitant reduction in serum HDL-C levels in obese rats. DISCUSSION: Thus, our observations highlight the role of vitamin A in reverse cholesterol transport through up-regulation of hepatic SR-BI receptors and, thereby, HDL-C homeostasis in obese rats of WNIN/Ob strain.