RESUMEN
This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.
Asunto(s)
Dislipidemias/diagnóstico , Dislipidemias/terapia , República Checa , Humanos , Guías de Práctica Clínica como Asunto , Sociedades MédicasRESUMEN
Hypertension is the most prevalent cardiovascular disease of the adult population and is closely associated with serious cardiovascular events. The burden of hypertension with respect to vascular and other organ damage is greater in women. These sex differences are not fully understood. The unique feature in women is their transition to menopause accompanied by profound hormonal changes that affect the vasculature that are also associated with changes of blood pressure. Results from studies of hormone replacement therapy and its effects on the cardiovascular system are controversial, and the timing of treatment after menopause seems to be important. Therefore, revealing potential sex- and sex hormone-dependent pathophysiological mechanisms of hypertension in experimental studies could provide valuable information for better treatment of hypertension and vascular impairment, especially in postmenopausal women. The experimental rat models subjected to ovariectomy mimicking menopause could be useful tools for studying the mechanisms of blood pressure regulation after menopause and during subsequent therapy.
Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Femenino , Masculino , Ratas , Animales , Menopausia/fisiología , Enfermedades Cardiovasculares/epidemiología , Terapia de Reemplazo de Hormonas , Presión Sanguínea/fisiologíaRESUMEN
Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the classical risk factors for MI are responsible for approximately 50 % of MI cases. Attention has therefore recently been attracted to those genetic variants that are not associated with conventional risk factors. One of them is the marker rs10757274 in the "genefree" zone on chromosome 9, which has been repeatedly recognized as a risk factor for development of MI in Western populations. We analysed the relationship between the rs10757274 variant on chromosome 9 and risk of the acute coronary syndrome (ACS) in Czech population. The rs10757274 (A > G) variant was successfully analysed (CR = 99.4 % for patients and 98.4 % for controls) by PCR-RFLP in consecutively examined 1,046 men and 281 women with ACS (age below 65 years) and in population-based controls - 1,162 men and 1,355 women (aged up to 65 years). ANOVA and χ2 were used for statistical analysis. We confirmed that GG homozygotes are more frequent (codominant model of analysis) among patients with myocardial infarction than in the control group both in men (28.5 % vs. 22.0 %, P = 0.0001, OR 1.73, 95 % CI 1.36-2.19) and women (32.0 % vs. 24.6 %, P = 0.02, OR 1.62, 95 % CI 1.13-2.34). However, rs10757274 polymorphism was not associated with the classical risk factors either in control population or in ACS patients. We conclude that the rs10757274 variant at 9p23.1 is an important genetic risk factor for ACS development in the Czech population.
Asunto(s)
Síndrome Coronario Agudo/genética , Cromosomas Humanos Par 9/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Adulto , Anciano , Estudios de Casos y Controles , República Checa , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Polimorfismo de Nucleótido Simple/genética , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
AIM: The incidence of the metabolic syndrome (MS) in women rises rapidly during the menopause, substantially increasing their cardiovascular risk and mortality. The aim of the study was to analyze menopausal changes in individual MS components and the parameter of insulin resistance (HOMA-IR). METHODS: A random population sample of 909 women aged 45-54 years, resident in Prague 4, was examined in an epidemiological study. After excluding women with gynecological hormone therapy or surgical therapy, the two groups of women were compared: women of reproductive age (REPRO, n = 245) vs. naturally postmenopausal women (POSTm, n = 149). RESULTS: The incidence of MS rose significantly in menopause (REPRO/POSTm 22.9 ± 2.6%/38.3 ± 4.0%; p < 0.001). However, a detailed analysis among the five components defining MS showed that increases were only seen in waist circumference (p < 0.0001) and triglycerides (p < 0.001). There was no increase in the other components or HOMA-IR. A detailed analysis showed an increase in HOMA-IR at levels above the median (REPRO/POSTm: low HOMA-IR 0.9/0.9, not significant; high HOMA-IR 1.8/2.1, p < 0.001) and an increase in the incidence of MS just in these high levels of HOMA-IR and those rising during menopause (REPRO/POSTm: low HOMA-IR 13.8%/18.7%, not significant; high HOMA-IR 30.9%/57.3%, p < 0.0001). In menopause, there was an increase in the clustered incidence (accompanying MS) of each of the five MS components at the expense of isolated incidence (not accompanying MS). CONCLUSION: The acceleration of MS incidence at the onset of menopause may be accompanied by an increase in insulin resistance only in the population at highest risk. Reproductive women entering the menopause with an isolated MS component are at high risk for developing additional risk factors during menopause.
Asunto(s)
Resistencia a la Insulina , Menopausia , Síndrome Metabólico/epidemiología , HDL-Colesterol/sangre , República Checa/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Obesidad Abdominal/epidemiología , Triglicéridos/sangre , Circunferencia de la CinturaRESUMEN
The INSIG2 (INSIG2 is primarily involved in the regulation of fatty acid and cholesterol synthesis) gene is suggested to be obesity related. An INSIG2 promoter variant, G-102A, has been detected and was demonstrated to be of potential functional significance. In two cohorts of middle-aged men, the association between this variant and BMI was suggested. We sought to replicate the association between the INSIG2 G-102A variant and BMI in three large Slavonic Caucasian populations. Further, we analysed the possible effect of this variant on BMI changes in a short-time intervention study. One thousand ninety-nine males and 1368 females (population- based Czech MONICA three-year cohort), 908 females from the 3PMFs study, together with 94 overweight (BMI > 27 kg/m2) females who underwent nine weeks of dietary/exercise intervention were genotyped for the INSIG2 G-102A variant using PCR-RFLP analysis. We could not detect any association between the INSIG2 G-102A variant and BMI or WHR with or without adjusting for age and gender in any population. Neither the BMI change nor anthropometric and lipid parameter changes were affected by the INSIG2 G-102A gene variant in intervened overweight females. However, MONICA females (but not males) carrying the common GG genotype had higher plasma levels of HDL cholesterol (GG homozygotes 1.51 ± 0.36 mmol/l vs. A allele carriers 1.45 ± 0.33; P < 0.05) in both surveys. Our results indicated that the G-102A INSIG2 polymorphism has no consistent effect on BMI in general populations, but could influence HDL cholesterol in females.
Asunto(s)
HDL-Colesterol/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Alelos , Índice de Masa Corporal , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Población BlancaRESUMEN
Among unique cardiovascular risk factors in women are complications during pregnancy, including miscarriage. Important risk factor is also genetic background. One of powerful candidate genes for cardiovascular disease of atherosclerotic origin (aCVD) is gene for connexin 37 (Cx37) with strong gene-environment interaction including smoking status, that is also strong risk factor for complications in pregnancy including spontaneous abortion (SA). We analyzed association between SA and Cx37 gene polymorphism (1019C>T; Pro319Ser) in 547 fetuses and its potential interaction with smoking status of mothers. Using genetic analyses from women from general population as controls, ORs for T allele, found in our previous studies to be protective against aCVD, were calculated. T allele carriers (fetuses), had OR 0.91 (95 % CI 0.72-1.14) and no interaction with smoking was observed. In conclusion, no significant association between Cx37 polymorphism and SA was observed and no modifying effect of smoking status on this association was detected.
Asunto(s)
Aborto Espontáneo/genética , Conexinas/genética , Adulto , Biomarcadores , Femenino , Feto , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Recién Nacido , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Embarazo , Factores de Riesgo , Fumar , Adulto Joven , Proteína alfa-4 de Unión ComunicanteRESUMEN
We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Fructosa/administración & dosificación , Glucosa/administración & dosificación , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Glucemia/análisis , Ácidos Grasos no Esterificados/sangre , Fructosa/metabolismo , Glucosa/metabolismo , Humanos , Insulina/sangre , Hígado/fisiopatología , Espectroscopía de Resonancia Magnética , Masculino , Triglicéridos/sangreRESUMEN
At present, the supposed association between venous thromboembolism and atherosclerosis has yet to be proven. However, no data are available from patients with thrombophilias. We evaluated the association between preclinical atherosclerosis and prevalence of thromboembolic events in patients with thrombophilias. Presence of preclinical atherosclerosis in common carotid and femoral arteries measured by ultrasound was assessed by Belcaro score (based mainly on the presence of plaques) and by measurements of intima media thickness in the same location in 109 patients (43 men, mean age 41.5+/-13 years) with established thrombophilias. Other parameters under the study were age, presence of traditional cardiovascular risk factors, anthropometric and clinical data including blood pressure measurements and medication. The differences between patients with (n=47) and without (n=62) thromboembolic events were assessed by paired t-test and chi square tests. In patients with a history of venous thromboembolism, body mass index and the prevalence of antihypertensive treatment (AT) were significantly higher than in patients without history of thromboembolism (BMI: 26.5+/-5.0 vs. 24.4+/-3.7 kg/m2; p=0.04, AT: 25.5 % vs. 8.1 %; p=0.013). No significant differences between groups were found regarding preclinical atherosclerosis. Overweight and hypertension, but not preclinical atherosclerosis, were more prevalent in patients with thrombophilias suffering from thromboembolism.
Asunto(s)
Enfermedades de las Arterias Carótidas/epidemiología , Trombofilia/epidemiología , Tromboembolia Venosa/epidemiología , Adulto , Índice de Masa Corporal , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Sobrepeso/epidemiología , Prevalencia , Factores de Riesgo , UltrasonografíaRESUMEN
The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n = 5), ovariectomized animals (n = 9), ovariectomized animals treated for 12 weeks (n = 10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n = 9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol.
Asunto(s)
Enfermedades de la Aorta/prevención & control , Aterosclerosis/prevención & control , LDL-Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Ovariectomía , Simvastatina/farmacología , Animales , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/patología , Aorta Torácica/efectos de los fármacos , Aorta Torácica/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/patología , Biomarcadores/sangre , HDL-Colesterol/sangre , Cricetinae , Modelos Animales de Enfermedad , Esquema de Medicación , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Lipoproteínas LDL/sangre , Mesocricetus , Simvastatina/administración & dosificación , Factores de Tiempo , Triglicéridos/sangreRESUMEN
Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Glucemia/metabolismo , Colesterol 7-alfa-Hidroxilasa/metabolismo , Ritmo Circadiano/fisiología , Insulina/sangre , Adulto , Anticolesterolemiantes/administración & dosificación , Ácido Quenodesoxicólico/administración & dosificación , Colestenonas/sangre , Colesterol/sangre , Resina de Colestiramina/administración & dosificación , Activación Enzimática , Ácidos Grasos no Esterificados/sangre , Fármacos Gastrointestinales/administración & dosificación , Humanos , Masculino , Valores de Referencia , Triglicéridos/sangreRESUMEN
The apoprotein E gene ranks among the most discussed candidate genes for cardiovascular disease. We studied whether the association between apoprotein E gene polymorphism and manifestation of acute coronary syndrome is modulated by the presence/absence of traditional cardiovascular risk factors. The population under study were 1066 patients (men under 65 years) admitted between 2006- 2009 to five coronary care units in Prague (GENetic DEtermination of Myocardial Infarction in Prague) and the control population (1066 age-matched men selected from the Czech population sample). The frequency of disadvantage genotype E4+ was significantly higher (P < 0.01) in acute coronary syndrome patients (22.38 %) than in controls (16.76 %). When the acute coronary syndrome group was step by step limited to non-smokers, non-diabetics and normotensive individuals, the odds ratio displayed a gradual increase from 1.35 (for the entire group) through 1.48 (non-smokers), 1.53 (non-smokers+non-diabetics) to 1.71 (non-smokers+non-diabetics+normotensives). The effect of the apoprotein E gene on the individual risk of acute coronary syndrome is nonhomogenous within the patient groups. This association of apoprotein E gene with acute coronary syndrome is strongly modified by the presence/absence of traditional cardiovascular factors of atherosclerosis in a high-risk Czech population.
Asunto(s)
Apolipoproteínas E/genética , Enfermedad Coronaria/genética , Adulto , Anciano , Checoslovaquia , Femenino , Genotipo , Humanos , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The antiviral activities of analogs of the double-stranded complex of polyinosinic and polycytidylic acids [poly(I).poly(C)], which is a potent interferon inducer, have been studied. Structural changes that modify the polymer backbone substantially, such as loops or 2' --> 5' phosphodiester bonds, lead to decreased antiviral activity. Unexpectedly, however, the complex of polyinosinic acid and poly(1-vinylcytosine), which is only a much more distantly related analog of poly(I) . poly(C), shows high activity. It is postulated that the high activity is related to the reduction of the charge/mass ratio and to the existence of this complex in an aggregated state; these are two factors that generally enhance the uptake of compo unds by cells.
Asunto(s)
Antivirales/farmacología , Polinucleótidos/farmacología , Virus de la Estomatitis Vesicular Indiana/efectos de los fármacos , Técnicas de Cultivo , Fibroblastos , Interferones/biosíntesis , Poli I-C/farmacología , Polinucleótidos/síntesis química , Polivinilos/farmacología , Cultivo de VirusRESUMEN
Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis.
Asunto(s)
Aterosclerosis/inmunología , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/inmunología , Mediadores de Inflamación/sangre , Inflamación/inmunología , Adulto , Factores de Edad , Aterosclerosis/genética , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inflamación/genética , Interleucina-6/sangre , Masculino , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 (APOA5) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 --> Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded.
Asunto(s)
Apolipoproteínas A/genética , Infarto del Miocardio/genética , Polimorfismo Genético , Triglicéridos/sangre , Animales , Apolipoproteína A-V , Apolipoproteínas/genética , Apolipoproteínas A/sangre , Modelos Animales de Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/genética , Masculino , Ratones , Ratones Noqueados , Infarto del Miocardio/sangre , Infarto del Miocardio/prevención & control , Fenotipo , Ratas , Medición de RiesgoRESUMEN
Coronary artery disease is a serious health problem worldwide caused by interactions between genetic and environmental risk factors. One of the candidate genes is the gene for apolipoprotein E. We present a case report of two young smoking and obese carriers (man 45 years and woman 32 years old) of the apolipoprotein E (p.Arg136Cys) mutation, but with no severe dyslipidaemias detected among 1,671 survivors (1,483 men, 188 women, aged 21-75 years) of acute coronary syndrome screened for genetic and traditional cardiovascular risk factors. Between acute coronary syndrome survivors, the mutation has not yet been described. Even though this mutation raises suspicion to be a risk factor for cardiovascular disease (based on previous publications), its frequency was very low and similar to the control population (12 detected carriers of the mutation within the 9,386 screened individuals). Therefore, whether this rare mutation is causal for the development of myocardial infarction needs to be further evaluated.
Asunto(s)
Apolipoproteínas E/genética , Predisposición Genética a la Enfermedad , Infarto del Miocardio/genética , Adulto , Anciano , Enfermedades Cardiovasculares/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de RiesgoRESUMEN
An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy.
Asunto(s)
Trasplante de Corazón/instrumentación , Trasplante de Corazón/métodos , Corazón Auxiliar , Miocardio/patología , Trasplante Heterotópico/instrumentación , Trasplante Heterotópico/métodos , Animales , Atrofia/patología , Atrofia/cirugía , Corazón/diagnóstico por imagen , Masculino , Ratas , Ratas Endogámicas LewRESUMEN
Advanced atherosclerotic changes can often resist even to very aggressive treatment. Although basic mechanisms of its origin and development are known, some important steps in this process are still waiting for more detailed explanation. Therefore, in addition to already proved aggressive lowering of LDL cholesterol, appropriate timing of atherosclerosis treatment is of the essence. Revealing different stages of atherosclerotic process, less or more sensitive to treatment is of primary importance; however, its detection is complicated by several facts including not exactly identifiable periods of quiescence and progression of atherosclerotic process. One of populations, study of which could add valuable information regarding this problem, are women in menopausal transition. Previously unsuccessful therapy with hormone replacement therapy is restudied with focus on the time of/after menopause. Now, it is supposed to be favorable in women soon, approximately less than 8 years, after menopause. In addition, the same principle - optimal timing of the intervention of traditional cardiovascular risk factors, especially lipids, could be also of importance. Therefore, menopausal transition could be optimal period for the intervention in women at risk. However, this approach is to be proved by evidence from controlled prospective studies focused on lifestyle and/or pharmacological intervention.
Asunto(s)
Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Terapia de Reemplazo de Hormonas/métodos , Menopausia/metabolismo , Posmenopausia/metabolismo , Animales , Aterosclerosis/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/prevención & control , Esquema de Medicación , Femenino , Terapia de Reemplazo de Hormonas/tendencias , Humanos , Menopausia/efectos de los fármacos , Posmenopausia/efectos de los fármacos , Factores de Riesgo , Factores de TiempoRESUMEN
Apolipoprotein A-V plays an important role in the determination of plasma triglyceride (TG) concentration. We aimed to determine whether polymorphisms -1131T>C (rs662799) and 56C>G (rs3135506) of the APOA5 gene have an impact on the course of postprandial lipemia induced by a fat load and a fat load with added glucose. Thirty healthy male volunteers, seven heterozygous for the -1131C variant and three for the 56G variant (HT) carriers, and 20 wild-type (WT) carriers underwent two 8-hour tests of postprandial lipemia - one after an experimental breakfast consisting of 75 g of fat and second after a breakfast consisting of 75 g of fat and 25 g of glucose. HT carriers had a higher postprandial response after fat load than WT carriers (AUC TG: 14.01+/-4.27 vs. 9.84+/-3.32 mmol*h/l, respectively, p=0.016). Glucose added to the test meal suppressed such a difference. Heterozygous carriers of the variants of APOA5 (-1131C and 56G) display more pronounced postprandial lipemia after pure fat load than WT carriers. This statistically significant difference disappears when glucose is added to a fat load, suggesting that meal composition modulates the effect of these polymorphisms on the magnitude of postprandial lipemia.
Asunto(s)
Apolipoproteína A-V/genética , Grasas de la Dieta/administración & dosificación , Variación Genética/genética , Glucosa/administración & dosificación , Periodo Posprandial/fisiología , Triglicéridos/sangre , Adulto , Azúcares de la Dieta/administración & dosificación , Heterocigoto , Humanos , MasculinoRESUMEN
Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80+/-1.11 vs. 5.76+/-1.06 mmol/l in Czechs; 5.32+/-1.32 vs. 5.71+/-1.08 mmol/l in Lithuanians; 4.88+/-1.05 vs. 5.38+/-1.13 mmol/l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles.
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Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/epidemiología , Colesterol/sangre , Síndrome Coronario Agudo/diagnóstico , Anciano , República Checa/epidemiología , Humanos , Kazajstán/epidemiología , Lituania/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.