RESUMEN
OBJECTIVES: The mean platelet volume (MPV) and red cell distribution width (RDW) have recently arisen interest because of their association with an increased cardiovascular risk. The aim of our study was, therefore, to determine whether an association exists between MPV, RDW and lipoprotein sub-fractions, and to show the impact of statin therapy on these new possible biomarkers of atherosclerotic risk. DESIGN AND METHODS: A cohort of 40 patients with hypercholesterolaemia (29 females, mean age 62.9±9 years), without previous hypolipidaemic treatment were enrolled. The patients were treated with atorvastatin 40 mg/day for 12 weeks. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density cholesterol (HDL-C), triglycerides (TG), LDL-C sub-fractions [large LDL-C 1-2 and small dense (sd)-LDL-C 3-7], apolipoproteins (apoA1, apoB), apoB/apoA1 ratio, atherogenic index of plasma (AIP), haematological parameters (including MPV, RDW) and safety parameters (renal, hepatic) were measured before and after 12 weeks of atorvastatin treatment. RESULTS: At baseline, a strong correlation between HDL-C, TG, sd-LDL-C, apoB, apoB/apoA1, and AIP with MPV (r=-0.55, p<0.001; r=0.57, p<0.001; r=0.73, p<0.001; r=0.41, p<0.05; r=0.52, p<0.001; r=0.61, p<0.001, respectively) and RDW (r=-0.49, p<0.001; r=0.62, p<0.001; r=0.67, p<0.001; r=0.41, p<0.05; r=0.43, p<0.05; r=0.65, p<0.001, respectively) was found. After 12 weeks of treatment with atorvastatin, MPV and RDW values underwent significant modification only in those patients displaying the strongest lipid-lowering effect. CONCLUSIONS: Values of MPV and RDW seem to reflect a pro-atherogenic lipoprotein profile mainly represented by the presence of sd-LDL-C.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Atorvastatina/uso terapéutico , Dislipidemias/tratamiento farmacológico , Índices de Eritrocitos/efectos de los fármacos , Volúmen Plaquetario Medio , Anciano , Apolipoproteína A-I/sangre , Apolipoproteína B-100/sangre , Aterosclerosis/sangre , Dislipidemias/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.
Asunto(s)
Aciltransferasas/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Citocininas/metabolismo , Lípidos de la Membrana/biosíntesis , Morfogénesis , Aciltransferasas/genética , Arabidopsis/genética , Arabidopsis/efectos de la radiación , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Citocininas/farmacología , Oscuridad , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Meristema/efectos de los fármacos , Meristema/genética , Meristema/crecimiento & desarrollo , Meristema/efectos de la radiación , Morfogénesis/efectos de los fármacos , Morfogénesis/efectos de la radiación , Mutación , Fenotipo , Plantones/efectos de los fármacos , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/efectos de la radiaciónRESUMEN
Treatment with statins to achieve target low-density lipoprotein cholesterol (LDL-C) levels is still associated with residual risk. Lipoprotein subfraction evaluation can provide additional information regarding atherogenicity in these individuals. Patients (n = 40) with hypercholesterolemia (29 females, mean age 63 years), without previous hypolipemic treatment, were treated with atorvastatin 40 mg/d for 3 months. Atorvastatin significantly reduced total cholesterol (6.7 ± 1.0 vs 4.6 ± 1.3 mmol/L, P < .001), LDL-C (4.3 ± 1.0 vs 2.6 ± 0.9 mmol/L, P < .001), triglycerides (1.8 ± 0.9 vs 1.5 ± 1.00 mmol/L, P < .05), small-dense LDL (sdLDL) fraction 3 to 7 (0.22 ± 0.37 vs 0.09 ± 0.16 mmol/L, P < .001), and apolipoprotein B (apoB; 1.0 ± 0.2 vs 0.74 ± 0.2 g/L, P < .001). There was a negative correlation of atherogenic index of plasma (AIP) with buoyant LDL-1 and LDL-2 (r = -.35; P < .05) and positive with sdLDL-3 to sdLDL-7 (r = .52, P < .001). Administration of atorvastatin 40 mg/d in patients with hypercholesterolemia caused a shift in sdLDL subfractions to large, buoyant subfractions. The AIP better correlated with sdLDL than apoB levels.