ABSTRACT
Objective: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport and atherosclerosis. The aim of this study was to evaluate the effects of HL -514C/T polymorphism on sub-clinical and established carotid atherosclerotic in hyperalphalipoproteinemic and control individuals. Methods: One hundred and sixty nine asymptomatic individuals (aged 47 ± 16 years), 71 hyperalphalipopro-teinemic (Hyper-A, HDL-C = 68mg/dL) and 98 controls (CTL, HDL-C< 68mg/dL) were selected by clinical and laboratory evaluations. Lipids and lipoproteins were measured by enzymatic methods. HL activity was measured in post-heparin plasma by a radiometric assay and HL-514C/T genotypes were analyzed by PCR. Carotid intima-media thickness (cIMT) was measured by Doppler ultrasonography. Results: No differences in HL -514C/T genotype frequencies were observed between the groups. HL -514C/T polymorphism did not contribute to variations in cIMT or atherosclerotic lesion frequencies in Hyper-A and controls. Furthermore, no interactions between HL-514C/T polymorphism and cIMT or atherosclerotic lesions were found. Conclusions: In hyperalphalipoproteinemic individuals the -514C/T polymorphism is not associated with significant variations in HDL-Cholesterol concentrations. Besides, it has no repercussions on carotid atherosclerosis, although hepatic lipase activity is significantly reduced. No financial conflicts of interest exist.
Objetivo: La Lipasa Hepática (HL) está implicada en el metabolismo de las lipoproteínas distintas y desempeña un papel en el transporte inverso del colesterol y la aterosclerosis. El objetivo de este estudio fue evaluar los efectos del polimorfismo HL-514 C/T en la aterosclerosis carotídea subclínica en los individuos e hiperalfalipoproteinémicos y controles establecidos. Métodos: Ciento sesenta y nueve sujetos asintomáticos (edad 47 ± 16 años), 71 hiperalfalipoproteinémicos (Hyper-A, HDL-C = 68mg/dL) y 98 controles (CTL, HDL-C <68mg/dL) fueron seleccionados por evaluaciones clínicas y de laboratorio. Lípidos y lipoproteínas se midieron por métodos enzimáticos. La actividad de la HL se midió en plasma después de la heparina por el método radiométrico, y los genotipos HL-514C/T se analizaron por PCR. El Grosor íntimo-medial carotídeo (cIMT) se midió mediante ecografía. Resultados: No hubo diferencias en las frecuencias de los genotipos HL-514 C/T se observó entre los grupos. Polimorfismo HL-514 C/T no ha contribuido a los cambios en cIMT o la frecuencia de las lesiones ateroscleróticas en Hyper-A y los controles. Por otra parte, no hay interacción entre el polimorfismo HL-514 C/T y cIMT ni fueron halladas lesiones ateroscleróticas. Conclusiones: El polimorfismo HL -514 C/T no está asociado con cambios significativos en el colesterol HDL en hiperalfalipoproteinémicos particulares y no tiene efecto en la arteriosclerosis carotídea a pesar de que la actividad de la HL ha sido reducida significativamente. Los autores declaran no poseer conflictos de interés.
ABSTRACT
We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios.