RESUMO
Considering the limited information about the role of hereditary predisposition to the development of uveal melanoma, we have performed an analysis of the frequencies of BARD1 (rs1048108, rs2229571, rs2070094) and BRIP1 (rs4986764) gene polymorphisms in patients with uveal melanoma and benign choroidal nevus in comparison with healthy volunteers (control). It has been found that the minor alleles of BRIP1 rs4986764 and BARD1 rs2070094 polymorphisms, as well as the homozygosity of T allele at the BARD1 rs1048108 locus are common genetic markers for the predisposition to uveal melanoma and benign choroidal nevus, while the homozygous genotype GG for the BARD1 rs2229571 polymorphism is a specific marker for the predisposition to uveal melanoma and progressive choroidal nevus. We have also found that the heterozygous genotype at BARD1 rs1048108 polymorphic locus is a specific marker for protection against uveal melanoma and progressive choroidal nevus. Thus, our results indicate the advisability of studying polymorphisms of the BARD1 gene (rs1048108, rs2229571, and rs2070094) and the BRIP1 gene (rs4986764) in patients with uveal melanoma and progressive choroidal nevus. The obtained findings can be used for forming risk groups, prevention of uveal melanoma, and differential diagnosis of intraocular neoplasms.
Assuntos
Neoplasias da Coroide , Nevo , Neoplasias Uveais , Humanos , Estudos de Casos e Controles , Neoplasias Uveais/genética , Proteína BRCA1/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
OBJECTIVE: To study the relationship between vitamin D deficiency, VDR gene polymorphism rs10735810 (A > G), and a missed abortion in the first trimester of gestation; to determine the predictors of its risk. RESEARCH METHODS: 178 women aged between 18 and 41 were surveyed. The main group consisted of patients with miscarriage (n = 101), verified at the hospital stage (O02.0; O02.1), which were stratified by I group (n = 58, patients with the first miscarriage) and II groups (n = 43, patients with repeated miscarriage). The control group (n = 77) consisted of women with a successful pregnancy (Z34.0), which subsequently ended in delivery at term with a live fetus. Patients were surveyed and data was extracted from primary medical records. The level of 25(OH)D in the blood serum was investigated by mass spectrometry (n = 99). Genotyping for the vitamin D receptor gene polymorphism rs10735810 (VDR A > G) was performed for 177 patients. Statistical data analysis was performed via Statistica 10 and SAS JMP 11 application packages, using single-factor prediction for quantitative and binary factors, ROC analysis, and CHAID decision tree construction. RESULTS OF THE STUDY: WE found that patients with miscarriage in the first trimester of gestation (n = 60) more frequently than those in the control group (n = 39) had vitamin D insufficiency (93.3% versus 76.9%, p = .0183) including its deficiency, occurring at 25(OH)D of blood <20 ng/ml (71.7% versus 51.3%, p = .0392). This pattern was found in patients with the first miscarriage, where significant differences in the frequency of vitamin D deficiency were also detected in comparison with the control group (80.0% versus 51.3%, p = .0026). No direct correlation was found between the frequency of miscarriages in the first trimester and the variant of the polymorphism of the vitamin D receptor gene (VDR A > G [rs10735810]); the GG genotype in patients with repeated miscarriages was even less frequent compared to the control group (14.0% versus 23.7%, p = .3344). However, the decision tree has identified four risk classes and has determined that the highest risk of missed abortion in the cohort studied is formed by three predicates: smoking, serum level 25(OH)D < 6.5 ng/ml and VDR AA and GG genotypes. CONCLUSION: The data obtained show that vitamin D insufficiency plays a pathogenetically significant role in early reproductive losses associated with miscarriages, both first and recurrent.
Assuntos
Aborto Habitual/etiologia , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Aborto Habitual/sangue , Aborto Habitual/genética , Adolescente , Adulto , Feminino , Humanos , Gravidez , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
Loss of cardiomyocytes due to apoptotic or necrotic death is an important component of the pathogenesis of heart failure. Initiation of apoptosis by the mitochondrial pathway depends on the balance between proapoptotic and antiapoptotic factors, in particular, Bax and Bcl-2. Cardiomyocyte apoptosis in essential hypertension is studied in sufficient details. At the same time, apoptotic processes in the myocardium in diabetes mellitus alone and in combination with essential hypertension remain poorly understood. Here we studied the expression of Bax and Bcl-2 in the left ventricular cardiomyocytes of 38-week-old male Wistar-Kyoto rats and 38- and 57-week-old SHR rats with essential hypertension, diabetes mellitus, and a combination of these pathologies. Insulin-dependent diabetes mellitus was modelled by a single parenteral administration of streptozotocin in a dose 65 mg/kg. Expression of Bax and Bcl-2 was assessed by the immunohistochemical method. In essential hypertension and diabetes mellitus, the apoptotic processes in the ventricular myocardium were enhanced, as is seen from the increase in the content of the proapoptotic factor Bax and a decrease in the expression of the antiapoptotic factor Bcl-2. However, in case of combined pathology, Bax content increased less markedly, while the expression of antiapoptotic Bcl-2 was significantly increased.
Assuntos
Diabetes Mellitus Tipo 1 , Hipertensão , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , EstreptozocinaRESUMO
Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.
Assuntos
Doença da Artéria Coronariana , Oclusão de Enxerto Vascular/genética , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Endotelina-1/genética , Enzimas Conversoras de Endotelina/genética , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Masculino , Neovascularização Patológica/epidemiologia , Neovascularização Patológica/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/genética , Receptor de Endotelina A/genética , Stents/efeitos adversosRESUMO
About 30% of male infertility is associated with genetic abnormalities. Genetic polymorphisms increase the level of individual susceptibility to adverse environmental factors and affect human reproductive function. AIM: To study associations of glutathione S-transferase GSTP1(Ile/Val) gene polymorphisms (A313G; rs1695) with the risk of pathospermia in men of the Moscow region. MATERIALS AND METHODS: We examined 138 men in the Moscow region (n=70 - proven pathospermia, n=68 - fertile men). We obtained genomic DNA from blood leukocytes and studied the gene polymorphisms of glutathione-S-transferase GSTP1 (Ile/Val) (A313G; rs1695) in real time. RESULTS: In the analysis of the distribution frequencies of polymorphisms GSTP1 (Ile/Val) (A>G rs1695), we revealed the predominance of the AA genotype in fertile men and the predominance of the GG genotype (homozygous minor allele) in men with pathospermia. However, we found no significant difference in these parameters between the compared groups of patients (p=0.344). For GSTP1 (Ile/Val) polymorphism (A313G, rs1695), significant differences in the distribution of genotype frequencies in the subgroup of men with teratospermia (2=7.00; p=0.03) were revealed. The frequency of allele G in the subgroup of men with teratospermia is statistically significantly different from the frequencies of alleles in the control group: 52% versus 30% (2=10,004; p=0.0015). In subgroups of men with azoospermia and asthenospermia, we did not find significant differences in the distribution of genotypes of GSTP1 polymorphism (rs1695) (p>0.05). DISCUSSION: Glutathione-S-transferase (GSTP1) is a multifunctional protein that protects sperm cells from the damaging effects of reactive oxygen species and xenobiotics. The Association of GSTP1 polymorphism (Ile/Val) (A313G, rs1695) with teratospermia explains the main stages of the pathogenesis of male infertility in this category of patients. CONCLUSION: Gene polymorphism GSTP1 (A313G, rs1695) can be considered a genetic marker of susceptibility to pathospermia in men.
Assuntos
Glutationa Transferase , Infertilidade Masculina , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Infertilidade Masculina/genética , Masculino , Moscou/epidemiologia , Polimorfismo Genético , Fatores de RiscoRESUMO
In cardiomyocytes, high molecular ATP-dependent HSP70 and HSP90 play an important role in protecting the myocardium from abnormal proteins that appear, in particular, due to activation of oxidative stress. Molecular chaperone HSP60 is of particular importance for cardiomyocytes as it is responsible for assembly of mitochondrial matrix proteins. We studied the peculiarities of expression of HSP60 in left ventricular cardiomyocytes in hypertension, insulin-dependent diabetes mellitus, and their combination. The experiment was performed on 38-week-old male Wistar-Kyoto and SHR (spontaneously hypertensive) rats aged 38-57 weeks. Insulin-dependent diabetes mellitus was modeled by a single parenteral administration of 65 mg/kg streptozotocin. Expression of HSP60 in left ventricular cardiomyocytes was evaluated by immunohistochemical methods. It was found that hypertension, diabetes mellitus, and their combination are associated with a significant decrease in the content of HSP60 in left ventricular cardiomyocytes in comparison with the control. This finding can be considered as a pathogenetic mechanism of myocardial damage induced by hypertension and diabetes mellitus.
Assuntos
Chaperonina 60/genética , Diabetes Mellitus Experimental/genética , Ventrículos do Coração/metabolismo , Hipertensão/genética , Proteínas Mitocondriais/genética , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Glicemia/metabolismo , Chaperonina 60/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Regulação da Expressão Gênica , Ventrículos do Coração/patologia , Hipertensão/complicações , Hipertensão/patologia , Imuno-Histoquímica , Insulina/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/patologia , Estresse Oxidativo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , EstreptozocinaRESUMO
A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.
Assuntos
Aborto Habitual/genética , DNA (Citosina-5-)-Metiltransferases/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Regiões Promotoras Genéticas/genética , Fatores de Risco , DNA Metiltransferase 3BRESUMO
The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Angiotensinogênio/genética , Hipertensão Induzida pela Gravidez/genética , Integrina beta3/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia , Adulto , Feminino , Humanos , Polimorfismo Genético/genética , Gravidez , Estudos ProspectivosRESUMO
Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.
Assuntos
Predisposição Genética para Doença , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Cálculos Renais/genética , Genótipo , Humanos , Hiperoxalúria Primária/terapia , Rim/fisiopatologia , Biologia Molecular , FenótipoRESUMO
Primary hyperoxaluria is a group of rare inherited diseases characterized by impaired oxalate metabolism with the early manifestation of urolithiasis and the development of the chronic kidney disease. The mutations in the AGXT, GRHPR, HOGA1 genes are attributable for different types of primary hyperoxaluria leading to the dysfunction of specific enzymes involved in the oxalate metabolism. The article summary the current data on the epidemiology, genetic and biochemical aspects of pathogenesis of the primary hyperoxaluria types 1-3. The variety of clinical signs and disease severity depend on the type of hyperoxaluria.
Assuntos
Hiperoxalúria Primária , Urolitíase , Humanos , Hiperoxalúria Primária/epidemiologia , Hiperoxalúria Primária/genética , Mutação , Urolitíase/epidemiologia , Urolitíase/genéticaRESUMO
Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.
Assuntos
Cálcio/urina , Hipertensão/urina , Potássio/urina , Sódio/urina , Animais , Biomarcadores/urina , Pressão Sanguínea , Hipertensão/fisiopatologia , Masculino , Ratos Endogâmicos SHRRESUMO
In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensification of cardiomyocyte autophagia, which attained maximum on postligation day 1.
Assuntos
Isquemia Miocárdica/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/fisiologia , Masculino , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Coelhos , Função Ventricular Esquerda/fisiologiaRESUMO
The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.
Assuntos
Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , Miocárdio/patologia , Coelhos , Pressão VentricularRESUMO
Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT, and ITGB3 genes were analyzed in patients with arterial hypertension coupled with metabolic syndrome (N=15) and compared with population data and corresponding parameters in patients with isolated hypertension (N=15). Increased frequency of genotype ID of ACE gene (hypertension predictor) was confirmed for both groups. In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in case of hypertension combined with metabolic syndrome, the frequency of genotypes A1166C and C1166C of the gene AGTR1 was higher in comparison with population data. Comparison of mutant allele frequencies in the two groups showed that at the 90% significance level allele T of the AGT gene was more frequent in hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the AGTR1 gene was more frequent in the group with isolated hypertension.
Assuntos
Hipertensão/genética , Síndrome Metabólica/genética , Polimorfismo Genético/genética , Idoso , Angiotensinogênio/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Integrina beta3/genética , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Sistema Renina-Angiotensina/genéticaRESUMO
We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy deficit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Hipertensão/metabolismo , Fosfocreatina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Piridinas/farmacologia , Proteína X Associada a bcl-2/genética , Animais , Apoptose/efeitos dos fármacos , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Picolinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Endogâmicos SHR , Proteína X Associada a bcl-2/metabolismoRESUMO
In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP significantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a significant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can reflect triggering of the adaptive response followed by its exhaustion.
Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Frequência Cardíaca/fisiologia , Hipertensão/fisiopatologia , Animais , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
The specific features of circadian rhythm of BP were investigated in freely moving male SHR rats using telemetry monitoring technique. BP was recorded in the abdominal aorta according to 24-h/4-month schedule. The data were obtained from 22, 26, 30, 34, and 38-week-old animals. Normotensive Wistar rats (22 weeks) served as the control. It was found that the mean 24-h, daytime, and nighttime systolic and diastolic BP in hypertensive rats significantly surpassed the control throughout the observation period and practically did not change during prolonged hypertension. Some prognostically negative changes in the circadian rhythm of the basic hemodynamics system parameters appeared with time. For instance, the maximum 24-h systolic BP significantly increased in comparison with the initial level.
Assuntos
Aorta Abdominal/fisiopatologia , Ritmo Circadiano , Hipertensão/fisiopatologia , Animais , Pressão Sanguínea , Diástole , Progressão da Doença , Frequência Cardíaca , Hemodinâmica , Masculino , Atividade Motora , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Sístole , TelemetriaRESUMO
Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits with renovascular arterial hypertension and spontaneously hypertensive rats were measured after 10-day administration of a macroergic compound phosphocreatine. Treatment with phosphocreatine prevented activation of caspase-3, but had no effect on caspase-8 during secondary and genetically determined arterial hypertension. Our results indicate that the intrinsic mechanism of the induction of the caspase cascade in myocardial cells dominates over the extrinsic pathway during both types of arterial hypertension. Energy deficit is one of the inducing factors of these processes.
Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Ventrículos do Coração/química , Hipertensão Renovascular/metabolismo , Miocárdio/metabolismo , Fosfocreatina/farmacologia , Animais , Cardiotônicos/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Hipertensão Renovascular/tratamento farmacológico , Hipertensão Renovascular/genética , Hipertensão Renovascular/fisiopatologia , Masculino , Fosfocreatina/metabolismo , Coelhos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Cardiomyocyte apoptosis and hypertrophy have been studied in the left and right ventricular myocardium of spontaneously hypertensive rats without treatment and after 10-day administration of the ETA-receptor antagonist BQ-123. It is established that BQ-123 prevents the activation of cardiomyocyte apoptosis and significantly decreases the extent of hypertrophy development in the left ventricular myocardium, but does not influence the same mechanisms in the right ventricular myocardium.
Assuntos
Anti-Hipertensivos/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Antagonistas do Receptor de Endotelina A , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor de Endotelina A/metabolismoRESUMO
Focal left ventricular ischemia was modeled in male Chinchilla rabbits. Activities of caspase-3 and caspase-8 in the left and right ventricular myocardium and myocardial contractility were studied after 1, 3, and 5 days. Caspase-3 activity increased significantly in the left ventricular peri-infarction zone and right ventricular myocardium, while caspase-8 activity did not differ from the control. Left ventricular contractility decreased significantly and the hemodynamic load of the right ventricle sharply increased. These results attest to induction of the internal (mitochondrial) pathway of apoptosis in myocardial cells most likely caused by left ventricular hypoxia and right ventricular overload.