ABSTRACT
ResumenLas lipoproteínas ricas en triglicéridos (TRL) comprenden los quilomicrones, las VLDL y sus remanentes. Las TRL son altamente heterogéneas, difiriendo en el tamaño, densidad, composición y riesgo cardiovascular asociado. La evidencia acumulada demuestra una fuerte correlación entre el riesgo de enfermedad cardiovascular (ECV) y el nivel de TAG en ayunas y no en ayunas (posprandial). Se han propuesto dos mecanismos por los cuales las TRL pueden incrementar la ateroesclerosis: los remanentes de TRL y las VLDL son capaces de penetrar la íntima arterial, pueden ser internalizados por los macrófagos y convertirlos en células espumosas. Segundo: durante la lipólisis de las TRL se liberan un número de lípidos inflamatorios que alteran la biología del endotelio. Los TAG no son directamente aterogénicos, pero representan un importante biomarcador de ECV a causa de su asociación con una alta concentración de partículas pequeñas y densas de LDL, niveles reducidos de colesterol HDL y con apo C-III, una proteína proinflamatoria y proaterogénica.
AbstractTriglyceride-rich lipoproteins (TRL) comprise chylomicrons, VLDL and their remnants. TRL are highly heterogeneous, differing in size, density, composition, and associated cardiovascular risk. Accumulating evidence demonstrates a strong correlation between the risk of cardiovascular disease (CVD) and both non-fasting (postprandial) and fasting plasma TAG level. Two mechanisms by which TRL might increase atherosclerosis are proposed: TRL remnants and VLDL are able to penetrate the arterial intima, can be internalized by macrophages and convert these cells into foam cells. Second: during lipolysis of TRL a number of inflammatory lipids are released that alter endothelial biology. TAG are not directly atherogenic but represent an important biomarker of CVD because of their association with a high concentration of small dense LDL particles, reduced HDL cholesterol levels, and with apo C-III, a proinflammatory and proatherogenic protein.
Subject(s)
Triglycerides , Atherosclerosis , Dyslipidemias , Apolipoprotein C-III , LipoproteinsABSTRACT
AIM:To investigate the effects of high plasma triglyceride (TG) caused by apolipoprotein C Ⅲ( ApoC Ⅲ) transgene on the occurrence and development of abdominal aortic aneurysm ( AAA) .METHODS:The animal models of hypercholesterolemia and hypercholesterolemia combined with hypertriglyceridemia were established by feeding high-fat diet to LDLR-/-and ApoC Ⅲ+LDLR-/-mice, respectively.AAA was induced in these mice by pancreatic elastase. By evaluating the incidence of AAA, relative maximal abdominal aortic diameter, disruption of the elastic lamellar structure and expression of matrix metalloproteinases ( MMPs) in the aorta walls of the AAA, the occurrence and development of AAA were compared in LDLR-/-and ApoC Ⅲ+LDLR-/-mice fed with either chow diet or high-fat diet.In addition, an in vitro TNF-α-induced aneurysmal microenvironment model on vascular smooth muscle cells ( VSMC) was used to study the impact of triglyceride-rich lipoproteins ( TRLs) from mice with normal or high contents of ApoCⅢon elastin protein expres-sion.RESULTS:Feeding the high-fat diet aggravated the severity of AAA in the LDLR-/-mice.ApoC Ⅲ+LDLR-/-mice fed with high-fat diet had less severe AAA than LDLR-/-mice fed with high-fat diet.TRLs inhibited degradation of VSMC elas-tin protein induced by TNF-α, and in vitro TRLs from the mice with high content of ApoC Ⅲ, compared to those with nor-mal content of ApoC Ⅲ, had better inhibitory effect on the degradation of elastin.CONCLUSION:High plasma TG caused by ApoC Ⅲtransgene alleviates AAA of the LDLR-/-mice induced by elastase and high-fat diet.The effect is probably attrib-uted to the hypertriglyceridemia caused by ApoC Ⅲtransgene.