RESUMEN
The review is devoted to hypercholesterolemia which is one of the leading risk factors for IHD. By its origin it can be primary and secondary. Three major mechanisms of primary hypercholesterolemia in humans are discussed. They are: low activity of LDL receptors, reduced affinity of LAL for receptors and overproduction of lipoproteins containing apo B. Depending on mechanism nonidentical molecular defects leading to cholesterol imbalance in cells or in circulating lipoproteins are occurred. The understanding of the nature and mechanisms of hypercholesterolemia development is of great clinical value, because having determined molecular defect and using drugs combinations the majority of patients are a success to have their lipids normal. Only in the case of homozygous familial hypercholesterolemia medicamentous treatment becomes secondary and the principal therapeutic methods are plasmapheresis or selective LDL apheresis. Gene therapy as a method of homozygous familial hypercholesterolemia correction is in forthcoming future.
Asunto(s)
Hiperlipoproteinemia Tipo II/genética , Apolipoproteínas B/genética , Apolipoproteínas E/genética , Terapia Genética , Humanos , Hiperlipoproteinemia Tipo II/terapia , Mutación , Receptores de LDL/fisiología , Factores de RiesgoRESUMEN
Several men were examined for association between restriction fragment length polymorphism (RELP) Xba I (exon 26) number of tandem repeats in 3'-hypervariable region of the apolipoprotein-B gene and serum levels of cholesterol and triglyceride. These two types of polymorphism were studied. An association of the Xba I site and alleles containing more repeats in the 3'-hypervariable region with higher cholesterol and triglyceride was observed. 32 patients with CHD aged 24-56 years were examined. All the patients are males with clinical picture of CHD (stable angina pectoris of II-III functional classes) and dyslipoproteinemia of II a, II b and IV types by D. S. Fredrickson. Xba-I polymorphism of apo-B gene was detected by DNA polymerase reaction method. The following Xba-I genotypes were distinguished: X1X1 (absence of Xba I site); X1X2 (heterozygosity on Xba I site) and X2X2 (homozygosity on Xba-I site). Lipantil (fenofibratte) was prescribed in a dose of 300 mg daily after meals (100 mg three times a day). Data obtained show that DNA polymorphism of apo-B gene not only influences plasma lipids concentration but also determines effectiveness of hypolipidemic therapy. Hypolipidemic effect of lipantil depends on Xba-I site presents in apo-B gene and is significantly expressed in homozygous patients with X1X1 genotype.
Asunto(s)
Apolipoproteínas B/genética , Fenofibrato/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Hipolipemiantes/uso terapéutico , Adulto , Anciano , Angina de Pecho/sangre , Angina de Pecho/tratamiento farmacológico , Angina de Pecho/genética , Secuencia de Bases , Cartilla de ADN , Genotipo , Humanos , Hiperlipidemias/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Isquemia Miocárdica/sangre , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/genética , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
With a purpose to study the state of platelet haemostasis and vasoactive prostanoids system 78 patients with ischemic heart disease aged 28 to 59 years were examined. Among them there were 22 patients with "isolated" hypo-alpha-cholesterolemia and 14 patients who had hypo-alpha-cholesterolemia combined with hypertriglyceridemia (HTG). The data obtained show that hypo-alpha-cholesterolemia is accompanied by platelet disorders aggravation and characterized by activated platelet percentage growth. There is a reverse relationship between alpha-cholesterol plasma level and activated platelet percentage (r = -0.52). There is a direct relationship between high-density lipoprotein cholesterol plasma level and concentration of stable prostacyclin metabolite (6-keto-PGF1 alpha) in plasma (r = 0.64). Hypo-alpha-cholesterolemia in combination with HTG is characterized by more significant disorders in prostacyclin-thromboxane system consisting in an increase of plasma thromboxane system consisting in an increase of plasma thromboxane A2 concentration (p < 0.001) and a decrease of 6-keto-PGF1 alpha plasma level (p < 0.05). An inverse apolipoprotein A-1 plasma level (r = -0.48) has been revealed in the group of patients who had hypo-alpha-cholesterolemia combined with HTG.
Asunto(s)
Plaquetas/fisiología , HDL-Colesterol/sangre , Hemostasis , Hipolipoproteinemias/sangre , Isquemia Miocárdica/sangre , Prostaglandinas/sangre , Adulto , Degranulación de la Célula , Humanos , Hipertrigliceridemia/sangre , Lípidos/sangre , Persona de Mediana Edad , Activación Plaquetaria , Agregación PlaquetariaRESUMEN
The paper presents a clinical and genealogical characterization of 50 probands suffering from coronary heart disease concurrent with various lipid metabolic disturbances and 211 first-degree relatives whose data have been obtained from the probands' histories while making up their pedigrees. The prevalence of atherosclerosis among the first-degree relatives has been demonstrated to be related to the nature of lipid metabolic disturbances in a proband. Some dyslipoproteinemias in the proband have been characterized by early onset of coronary heart disease, stroke, and their grave course in close relatives.
Asunto(s)
Colesterol/sangre , Enfermedad Coronaria/etiología , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo IV/complicaciones , Hipolipoproteinemias/complicaciones , Lipoproteínas HDL/sangre , Adulto , Anciano , Enfermedad Coronaria/sangre , Enfermedad Coronaria/genética , Susceptibilidad a Enfermedades , Femenino , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo IV/genética , Hipolipoproteinemias/genética , Lipoproteínas HDL/deficiencia , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Recent data and concepts on the structure and functioning of apolipoprotein genes as well as on the role of hereditary factors in pathogenesis of atherosclerosis are reviewed. The most important variants of inherited disorders in the system of apolipoproteins promoting the development of atherosclerosis are considered. Special attention is paid to the RFLP of apolipoprotein genes which serves as a peculiar genetic background, increasing probability of the atherosclerosis development in certain individuals.
Asunto(s)
Apolipoproteínas/genética , Arteriosclerosis/genética , Apolipoproteínas/biosíntesis , Arteriosclerosis/metabolismo , Reordenamiento Génico/genética , Humanos , Mutación/genética , Polimorfismo Genético/genética , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
In an 8-month-old baby, one-stage correction of an atrial septal defect, multiple right and left atrial aneurysms and non-paroxysmal ectopic right atrial tachycardia was performed. An ectopic focus of atrial tachycardia was localized by a pre- and intraoperative electrophysiological study. Postoperatively, the patient's clinical status improved significantly.