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1.
Medicine (Baltimore) ; 99(50): e22418, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327224

RESUMO

Hypertension (HT) has recently been defined as a systolic blood pressure (BP) of ≥130 mm Hg and/or a diastolic BP of ≥80 mm Hg. It is important to further understand the pathophysiology of essential HT as its proportion is larger among most of the diagnosed HT cases. The apelin and apelin receptor (APLNR) are known to play roles in regulating BP, but the putative associations of single nucleotide polymorphisms in the APLNR gene with the risk of development of essential HT have not yet been fully investigated. Herein, we conducted a meta-analysis to investigate the relationship between single nucleotide polymorphisms in the APLNR gene and the risk of essential HT.We conducted a search in the PubMed and Web of Science databases for eligible studies. The pooled odds ratios (ORs) with their 95% confidence intervals (CI) were calculated using random-effects models when heterogeneity was expected across the studies. Otherwise, fixed-effect models were used.Regarding the SNP rs7119375, 5 studies were analyzed, which included a total of 3567 essential HT patients and 3256 healthy controls. Four of the 5 studies were from China and 1 was from Mexico. The meta-analysis showed the existence of a significant association between the AA genotype of rs7119375 and the risk of developing essential HT in the Chinese population, as determined using additive and recessive models (OR, 2.11; 95% CI, 1.12-3.96; I = 86% for AA vs GG. OR, 1.53; 95% CI, 1.21-1.94; I = 28% for AA vs AG. OR, 1.88; 95% CI, 1.13-3.12; I = 79% for AA vs AG + GG).Our study showed, for the first time, the existence of an association between rs7119375 and the risk of development of essential HT in the Chinese population, although the sample size was small and there was considerable population heterogeneity. The apelin/APLNR system could be a novel therapeutic target for the treatment of essential HT, and more studies are warranted to further investigate the association.


Assuntos
Receptores de Apelina/genética , Hipertensão Essencial/genética , Polimorfismo de Nucleotídeo Único/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/fisiopatologia , Feminino , Genótipo , Humanos , Masculino , México/epidemiologia , Fatores de Risco
2.
Medicine (Baltimore) ; 99(46): e23164, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181690

RESUMO

BACKGROUND: Recently, many studies have been conducted to investigate the relationship between the A46G polymorphism in the ß2-adrenergic receptor (ADRB2) gene and essential hypertension risk in the Chinese population. However, the results of previous studies were conflicting. OBJECTIVES: The present study aimed to investigate the association between the ADRB2 A46G polymorphism and the risk of essential hypertension in the Chinese population. METHODS: We performed a systematic search of possible relevant studies on PubMed, Embase, Ovid, Web of Science, China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc databases up to January 3, 2020. Two authors independently extracted information from included articles and assessed the quality of each study by the use of the Newcastle-Ottawa Scale. According to the extent of interstudy heterogeneity, either a random-effect model or a fixed-effect model was used to calculate the combined odds ratio (OR) and 95% confidence interval (CI). RESULTS: Finally, 16 studies containing 3390 cases and 2528 controls were included in our meta-analysis. Significant associations were found between the ADRB2 A46G polymorphism and essential hypertension risk in the Chinese population under four genetic models: allele genetic model (OR: 1.14, 95% CI: 1.06-1.23, P = .001, Pheterogeneity = .09), homozygote genetic model (OR: 1.29, 95% CI: 1.11-1.51, P = .001, Pheterogeneity = .25), dominant genetic model (OR: 1.17, 95% CI: 1.05-1.32, P = .005, Pheterogeneity = .04), and recessive genetic model (OR: 1.21, 95% CI: 1.05-1.38, P = .007, Pheterogeneity = .72). CONCLUSION: The ADRB2 A46G polymorphism may increase the risk of essential hypertension in the Chinese population.


Assuntos
Hipertensão Essencial , Receptores Adrenérgicos beta 2/genética , Grupo com Ancestrais do Continente Asiático/genética , Hipertensão Essencial/etnologia , Hipertensão Essencial/genética , Predisposição Genética para Doença/etnologia , Humanos , Polimorfismo de Nucleotídeo Único
3.
DNA Cell Biol ; 39(11): 2095-2101, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33016778

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is known as the counter-regulator of the renin-angiotensin system, it cleaves angiotensin II to render Ag 1-7, a potent vasodilator with multiple roles in cardiovascular protection. A few studies have pinpointed ACE2 polymorphisms and their relationship with heart function and hypertension in a sex-dependent manner. These observations still lack replication mostly for admixed populations. This study aimed to report minor allele frequencies of four ACE2 intron variants, rs2285666, rs2048683, rs2106809, and rs4240157, derived from previous research using the GSA, v1.0, microarray in 1231 hypertensive and nonhypertensive patients. Logistic and multiple linear regression models were developed to identify potential associations with hypertension status and systolic and diastolic blood pressure (SBP and DBP). Allele frequency differences were identified for ACE2 rs2048683 and rs4240157 in populations with European ancestry and people of the Americas. Regression analyses identified a significant association of ACE2 rs2048683 and rs4240157 with SBP/DBP in males or females. Our observations confirm sex differences in ACE2 genetic associations with SBP and DBP and contribute to the collection of genetic variation in ACE2 for admixed populations.


Assuntos
Pressão Sanguínea/genética , Hipertensão Essencial/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Hipertensão Essencial/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
4.
Medicine (Baltimore) ; 99(23): e20552, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502021

RESUMO

BACKGROUND: To assess the association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension (EH) in a Chinese Han population. METHOD: Peripheral blood samples were extracted from 422 EH patients and 280 normotensive (NT) patients in a Chinese Han population. A whole blood genomic DNA extraction kit was used to extract genomic DNA from the blood samples. Polymerase chain reaction restriction fragment length polymorphism was used to detect the rs402007 polymorphism of a disintegrin and metalloproteinase with thrombospondin type motifs 1 gene and the rs9619311 polymorphism of the tissue inhibitor of metalloproteinase-3 gene. The distributions of the genotypes and alleles between the 2 study groups (EH and NT) were compared. The main risk factors for EH were determined by using logistic regression analysis. The effects of gene-gene and gene-smoking interactions on EH were analyzed using multifactor dimensional reduction. RESULTS: The frequencies of the rs402007 GC + CC genotype and the C allele were significantly different between the EH and NT groups (0.68 vs 0.57, χ = 8.99, P = .003, odds ratio [OR] = 1.19; 0.45 vs 0.32, χ = 22.16, P < .001, OR = 1.38). The frequencies of the rs9619311 TC + CC genotype and the C allele were also significantly different between the 2 groups (0.33 vs 0.25, χ = 4.51, P = .04, OR = 1.44; 0.18 vs 0.13, χ = 7.03, P = .01, OR = 1.50). Logistic regression analysis suggests that the rs402007 and rs9619311 polymorphisms are independent risk factors for EH (OR = 2.37, 1.86; P < .001, respectively). The multifactor dimensionality redundant analysis results showed that the interaction among rs402007, rs9619311, and smoking was statistically significant (P = .001). CONCLUSIONS: A disintegrin and metalloproteinase with thrombospondin type motifs 1 rs402007 and tissue inhibitor of metalloproteinase-3 rs9619311 polymorphisms are associated with EH in a Chinese Han population, and there was a positive interaction among rs402007, rs9619311, and smoking.


Assuntos
Proteína ADAMTS1/genética , Hipertensão Essencial/genética , Grupos Étnicos/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fumar/epidemiologia , Inibidor Tecidual de Metaloproteinase-3/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Hipertensão Essencial/epidemiologia , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
5.
Altern Ther Health Med ; 26(S2): 54-55, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32412919

RESUMO

By April 28th 2020, the global number of people that were viciously infected with the newfound novel corona virus (COVID-19) stood at a staggering 3 077 133 cases, as per the confirmed data released by the WHO. It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases. Thus, there might be severe myocarditis, that may result in acute heart failure and cardiac complexities in the elderly subjects.


Assuntos
Fatores Etários , Infecções por Coronavirus/epidemiologia , Hipertensão Essencial/genética , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Fatores Sexuais , Grupo com Ancestrais do Continente Asiático , Betacoronavirus , China , Feminino , Humanos , Masculino , Pandemias , Polimorfismo de Nucleotídeo Único , Fatores de Risco
6.
BMC Med Genet ; 21(1): 105, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414374

RESUMO

BACKGROUND: Nuclear genome or family mitochondrial screening system has become the hot focus of studies into essential hypertension. The role of mitochondrial DNA (mtDNA) in sporadic Chinese patients with hypertension has not been fully understood. The study was to evaluate the associations of mtDNA mutations with maternally inherited essential hypertensive subjects in China. METHODS: From June 2009 to June 2016, a total of 800 gender-matched Chinese patients with maternally inherited essential hypertension (MIEH) and control group were 1:1 enrolled in this case-control study. Genomic DNA was extracted from each person's peripheral blood cells. The main mtDNA locations for MIEH were screened with oligodeoxynucleotides 3777-4679 bp, analyzed and compared with the updated consensus Cambridge Sequence. Pathogenic mtDNA mutations were identified from the mitochondrial map. RESULTS: MIEH subjects presented significantly higher values than those of control group in abdominal circumference (AC), waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and renal function (P < 0.05). MIEH subjects carried more amino acid changes and coding sequence variants (P < 0.01) than control group. The allele frequencies of the eight single nucleotide polymorphisms (SNPs) were significantly different between the two groups, including m.3970 C > T, m.4048G > A, m.4071C > T, m.4086C > T, m. 4164A > G and m.4248 T > C in ND1 gene, and m.4386 T > C and m.4394C > T in tRNAGln gene(P < 0.001). Fifty-five homoplasmic or heteroplasmic mutations were detected in 5 genes: ND1, tRNAIle, tRNAMet, tRNAGln and ND2 gene. The ND1 gene was the main mutation site, where the most mtDNA mutation was m.3970 C > T. CONCLUSIONS: The mtDNA mutations were involved in the process of MIEH. We identified mitochondrial genetic characteristics in MIEH patients in China. The present research serves as a solid foundation for further detailed research on the association between MIEH and mitochondrial dysfunction, and their causal relationship in Chinese and other populations with a similar lifestyle.


Assuntos
DNA Mitocondrial , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/genética , Genes Mitocondriais , Estudos de Associação Genética , Predisposição Genética para Doença , Herança Materna , Mutação , Idoso , Alelos , Estudos de Casos e Controles , Hipertensão Essencial/metabolismo , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Int Heart J ; 61(3): 562-570, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350201

RESUMO

Aldehyde dehydrogenase-2 (ALDH2) rs671 G>A polymorphism can influence the activity of ALDH2 and may be associated with the risk of essential hypertension (EH). Although many previous studies have explored such a relationship, the conclusion is still controversial.The PubMed, Embase, and China National Knowledge Infrastructure databases were searched on the ALDH2 gene and EH. We used the Newcastle-Ottawa Scale to evaluate the quality of the study. Then we calculated the strength of relationship between ALDH2 rs671 mutation and EH by utilizing odds ratios and 95% confidence intervals. Besides, subgroup analysis and sensitivity analysis were performed and the publication bias was assessed.There were 12 studies containing 8153 cases and 10,162 controls. Our meta-analysis showed significant association between ALDH2 rs671 polymorphism and EH in four genetic models (the allele model, the homozygote model, the heterozygote model, and the dominant model), whereas it did not indicate this connection in the recessive model. However, a trend of decreased risk still could be seen. Furthermore, we also found an obvious association between rs671 mutation and the risk of EH in the male group than in the female group in all five genetic models.We concluded that ALDH2 rs671 G>A polymorphism may decrease the risk of EH. Furthermore, susceptibility to EH reduced in males but not in females. As a variant in ALDH2, rs671 G>A could be an attractive candidate for genetic therapy of EH. In addition, more case-control studies should be conducted to strengthen our conclusion and evaluate the gene-gene and gene-environment interactions between the ALDH2 gene and EH.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Hipertensão Essencial/genética , Humanos , Polimorfismo de Nucleotídeo Único
8.
BMC Cardiovasc Disord ; 20(1): 169, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293282

RESUMO

BACKGROUND: To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia. METHODS: A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction. RESULTS: Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07-55.58)] and AGT [OR = 3.53; 95% CI (1.02-12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03-27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21-22.30), р = 0.029]. CONCLUSION: An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.


Assuntos
Pressão Arterial/genética , Hipertensão Essencial/genética , Povos Indígenas/genética , Polimorfismo de Nucleotídeo Único , Renina/genética , Adulto , Idoso , Biomarcadores/sangue , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/etnologia , Hipertensão Essencial/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Renina/sangue , Fatores de Risco , Sibéria/epidemiologia
9.
BMC Med Genet ; 21(1): 55, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188413

RESUMO

BACKGROUND: Glutathione S-transferases play a key role in the detoxification of persistent oxidative stress products which are one of several risks factors that may be associated with many types of disease processes such as cancer, diabetes, and hypertension. In the present study, we characterize the null genotypes of GSTM1 and GSTT1 in order to investigate the association between them and the risk of developing essential hypertension. METHODS: We conducted a case-control study in Burkina Faso, including 245 subjects with essential hypertension as case and 269 control subjects with normal blood pressure. Presence of the GSTT1 and GSTM1 was determined using conventional multiplex polymerase chain reaction followed by gel electrophoresis analysis. Biochemical parameters were measured using chemistry analyzer CYANExpert 130. RESULTS: Chi-squared test shows that GSTT1-null (OR = 1.82; p = 0.001) and GSTM1-active/GSTT1-null genotypes (OR = 2.33; p <  0.001) were significantly higher in cases than controls; the differences were not significant for GSTM1-null, GSTM1-null/GSTT1-active and GSTM1-null/GSTT1-null (p > 0.05). Multinomial logistic regression revealed that age ≥ 50 years, central obesity, family history of hypertension, obesity, alcohol intake and GSTT1 deletion were in decreasing order independent risk factors for essential hypertension. Analysis by gender, BMI and alcohol showed that association of GSTT1-null with risk of essential hypertension seems to be significant when BMI < 30 Kg/m2, in non-smokers and in alcohol users (all OR ≥ 1.77; p ≤ 0.008). Concerning GSTT1, GSTM1 and cardiovascular risk markers levels in hypertensive group, we found that subjects with GSTT1-null genotype had higher waist circumference and higher HDL cholesterol level than those with GSTT1-active (all p <  0.005), subjects with GSTM1-null genotype had lower triglyceride than those with GSTM1-active (p = 0.02) and subjects with the double deletion GSTM1-null/GSTT1-null had higher body mass index, higher waist circumference and higher HDL cholesterol than those with GSTM1-active/GSTT1-active genotype (all p = 0.01). CONCLUSION: Our results confirm that GSTT1-null genotype is significantly associated with risk of developing essential hypertension in Burkinabe, especially when BMI < 30 Kg/m2, in non-smokers and in alcohol users, and it showed that the double deletion GSTM1-null/GSTT1-null genotypes may influence body lipids repartition.


Assuntos
Hipertensão Essencial/genética , Glutationa Transferase/genética , Polimorfismo Genético , Deleção de Sequência , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Burkina Faso/epidemiologia , Estudos de Casos e Controles , Hipertensão Essencial/sangue , Hipertensão Essencial/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lipídeos/sangue , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/sangue , Fumar/epidemiologia
10.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054074

RESUMO

Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.


Assuntos
Hipertensão Essencial/etiologia , Adulto , Animais , Metilação de DNA , Epigênese Genética , Hipertensão Essencial/genética , Hipertensão Essencial/metabolismo , Hipertensão Essencial/patologia , Código das Histonas , Humanos , Microbiota , Estresse Oxidativo
11.
Clin Exp Hypertens ; 42(1): 36-42, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30706734

RESUMO

Background: Essential hypertension is a multifactorial disease with high morbidity. The researches on the influence of genes on the disease are still in its infancy, and the mechanism of gene regulation is not clear. MiRNAs are key molecules that regulate the expression control of protein-coding or protein-non-coding RNA. It may be an important biological molecule risk factor for essential hypertension.Methods: A case-control study with 98 EH and 98 non-EH was conducted in our experiment. The candidate miRNAs including miR-10a-5p and miR-497-5p were detected and verified by qRT-PCR.Results: The expression level of miRNA in EH cases was significantly lower than the healthy control (P = 0.005). In addition, the relative expression of miR-10a-5p was closely positive correlated with DBP (r = 0.162, P = 0.023) and SBP (r = 0.223, P = 0.002). After adjusting confound factors, the result of the logistic regression indicated that hypo-expression of miR-10a-5p is a risk factor for EH (OR(95%CI) = 1.676(1.302,2.157), adjusted P < 0.0001). And the ROC analysis shows that the combined line with BMI and miR-10a-5p was a values marker for EH (AUC: 0.728, P < 0.0001).Conclusions: Lower expression of miR-10a-5p, as the key role, is significantly related to the risk of EH and maybe as a potential biomolecule for EH.


Assuntos
Hipertensão Essencial/genética , MicroRNAs/genética , Idoso , Área Sob a Curva , Biomarcadores , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
12.
Circ Res ; 126(4): 439-452, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31852393

RESUMO

RATIONALE: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in the regulation of metabolic and antioxidant functions which are associated with hypertension, and cardiovascular disease risk factors diminish Sirt3 level. OBJECTIVE: We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction in hypertension, but increased Sirt3 protects vascular function and decreases hypertension. METHODS AND RESULTS: To test the therapeutic potential of targeting Sirt3 expression, we developed new transgenic mice with global Sirt3OX (Sirt3 overexpression), which protects from endothelial dysfunction, vascular oxidative stress, and hypertrophy and attenuates Ang II (angiotensin II) and deoxycorticosterone acetate-salt induced hypertension. Global Sirt3 depletion in Sirt3-/- mice results in oxidative stress due to hyperacetylation of mitochondrial superoxide dismutase (SOD2), increases HIF1α (hypoxia-inducible factor-1), reduces endothelial cadherin, stimulates vascular hypertrophy, increases vascular permeability and vascular inflammation (p65, caspase 1, VCAM [vascular cell adhesion molecule-1], ICAM [intercellular adhesion molecule-1], and MCP1 [monocyte chemoattractant protein 1]), increases inflammatory cell infiltration in the kidney, reduces telomerase expression, and accelerates vascular senescence and age-dependent hypertension; conversely, increased Sirt3 expression in Sirt3OX mice prevents these deleterious effects. The clinical relevance of Sirt3 depletion was confirmed in arterioles from human mediastinal fat in patients with essential hypertension showing a 40% decrease in vascular Sirt3, coupled with Sirt3-dependent 3-fold increases in SOD2 acetylation, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity, VCAM, ICAM, and MCP1 levels in hypertensive subjects compared with normotensive subjects. CONCLUSIONS: We suggest that Sirt3 depletion in hypertension promotes endothelial dysfunction, vascular hypertrophy, vascular inflammation, and end-organ damage. Our data support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertension.


Assuntos
Hipertensão Essencial/metabolismo , Coração/fisiopatologia , Inflamação/metabolismo , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo , Sirtuína 3/metabolismo , Angiotensina II , Animais , Acetato de Desoxicorticosterona , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hipertensão Essencial/induzido quimicamente , Hipertensão Essencial/genética , Feminino , Inflamação/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/metabolismo , Proteínas Mitocondriais/genética , Miocárdio/metabolismo , Miocárdio/patologia , Sirtuína 3/genética
13.
Genomics ; 112(1): 764-768, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31102703

RESUMO

CYP24A1, Vitamin D 24-hydroxylase catabolizes 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D to 24-hydroxylated vitamin D products. It is widely known that low Vitamin D can lead to increased renal renin and angiotensin II production, consequently elevating blood pressure or development of essential hypertension (EH). We have conducted an investigation on hypertensives and controls to evaluate the association of the gene variant, CYP24A1 rs2762939 and 25(OH)D in an Indian population with EH. On gender-based stratification, with multivariate logistic analysis after adjustment for covariates, the CYP24A1 rs2762939 CC variant showed a higher risk of EH in males (aOR = 3.141, CI 1.164-8.478, P = .024) while females illustrated an inverse association with EH (aOR = 0.398, CI 0.172-0.092, P = .031). The 25(OH)D levels among the three genotypes of hypertensives substantiate these results. Our results clearly suggest that gender, CYP24A1 rs2762939, and Vitamin D status may play a significant role in disease susceptibility towards EH in Indian population.


Assuntos
Hipertensão Essencial/etiologia , Renina/sangue , Vitamina D3 24-Hidroxilase/genética , Vitamina D/análogos & derivados , Adulto , Idoso , Estudos de Casos e Controles , Hipertensão Essencial/sangue , Hipertensão Essencial/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Caracteres Sexuais , Vitamina D/sangue
14.
Artigo em Inglês | MEDLINE | ID: mdl-31805646

RESUMO

Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like (CAPG) gene, adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (TIMP3), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) CAPG, ADD1, TIMP3, MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.


Assuntos
Metilação de DNA , Hipertensão Essencial/genética , Feminino , Genótipo , Humanos
15.
Bull Exp Biol Med ; 168(1): 79-83, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31768780

RESUMO

The risk of essential arterial hypertension was assessed in carriers of the NOS2 gene variants (rs1800482 (-954G>C), rs3730017 (C>T)). In subjects carrying C allele (rs1800482), the risk for essential arterial hypertension developing was higher by 1.7 times (OR=1.712, 95%CI 1.07-2.74), while the presence of T-allele (rs3730017) had a protective effect (OR=0.304, 95%CI 0.192-0.482). In patients with essential arterial hypertension, the presence of the C allele (rs1800482) was associated with a higher content of NO metabolites in the blood plasma. A positive correlation was found between the plasma content of nitrites and nitrates and the level of transcripts of VCAM1, ICAM1 genes in peripheral blood leukocytes. We found the influence of the C allele carriership on the expression VCAM1 and ICAM1 genes in patients with essential hypertension. It was hypothesized that this polymorphic site in the NOS2 gene can be involved in the development of endothelial dysfunction and essential arterial hypertension through modulation of NO level under condition of inflammation.


Assuntos
Hipertensão Essencial/genética , Predisposição Genética para Doença/genética , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade
16.
Int J Mol Sci ; 20(17)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450834

RESUMO

The aim of this study was to investigate the hemodynamic effects of SKA-31, an activator of the small (KCa2.x) and intermediate (KCa3.1) conductance calcium-activated potassium channels, and to evaluate its influence on endothelium-derived hyperpolarization (EDH)-KCa2.3/KCa3.1 type relaxation in isolated endothelium-intact small mesenteric arteries (sMAs) from spontaneously hypertensive rats (SHRs). Functional in vivo and in vitro experiments were performed on SHRs or their normotensive controls, Wistar-Kyoto rats (WKY). SKA-31 (1, 3 and 10 mg/kg) caused a brief decrease in blood pressure and bradycardia in both SHR and WKY rats. In phenylephrine-pre-constricted sMAs of SHRs, SKA-31 (0.01-10 µM)-mediated relaxation was reduced and SKA-31 potentiated acetylcholine-evoked endothelium-dependent relaxation. Endothelium denudation and inhibition of nitric oxide synthase (eNOS) and cyclooxygenase (COX) by the respective inhibitors l-NAME or indomethacin, attenuated SKA-31-mediated vasorelaxation. The inhibition of KCa3.1, KCa2.3, KIR and Na+/K+-ATPase by TRAM-34, UCL1684, Ba2+ and ouabain, respectively, reduced the potency and efficacy of the EDH-response evoked by SKA-31. The mRNA expression of eNOS, prostacyclin synthase, KCa2.3, KCa3.1 and KIR were decreased, while Na+/K+-ATPase expression was increased. Collectively, SKA-31 promoted hypotension and vasodilatation, potentiated agonist-stimulated vasodilation, and maintained KCa2.3/KCa3.1-EDH-response in sMAs of SHR with downstream signaling that involved KIR and Na+/K+-ATPase channels. In view of the importance of the dysfunction of endothelium-mediated vasodilatation in the mechanism of hypertension, application of activators of KCa2.3/KCa3.1 channels such as SKA-31 seem to be a promising avenue in pharmacotherapy of hypertension.


Assuntos
Benzotiazóis/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Hipertensão Essencial/genética , Hipertensão Essencial/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/agonistas , Canais de Potássio Ativados por Cálcio de Condutância Baixa/agonistas , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Hipertensão Essencial/fisiopatologia , Ratos , Ratos Endogâmicos SHR
17.
Int J Med Sci ; 16(6): 793-799, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337952

RESUMO

Background: Essential hypertension (EH) is a chronic disease of universal high prevalence and a well-established independent risk factor for cardiovascular and cerebrovascular events. The regulation of blood pressure is crucial for improving life quality and prognoses in patients with EH. Therefore, it is of important clinical significance to develop prediction models to recognize individuals with high risk for EH. Methods: In total, 965 subjects were recruited. Clinical parameters and genetic information, namely EH related SNPs were collected for each individual. Traditional statistic methods such as t-test, chi-square test and multi-variable logistic regression were applied to analyze baseline information. A machine learning method, mainly support vector machine (SVM), was adopted for the development of the present prediction models for EH. Results: Two models were constructed for prediction of systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. The model for SBP consists of 6 environmental factors (age, BMI, waist circumference, exercise [times per week], parental history of hypertension [either or both]) and 1 SNP (rs7305099); model for DBP consists of 6 environmental factors (weight, drinking, exercise [times per week], TG, parental history of hypertension [either and both]) and 3 SNPs (rs5193, rs7305099, rs3889728). AUC are 0.673 and 0.817 for SBP and DBP model, respectively. Conclusions: The present study identified environmental and genetic risk factors for EH in northern Han Chinese population and constructed prediction models for SBP and DBP.


Assuntos
Hipertensão Essencial/diagnóstico , Predisposição Genética para Doença , Modelos Biológicos , Adolescente , Adulto , Fatores Etários , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Pressão Sanguínea/genética , Índice de Massa Corporal , Estudos Transversais , Hipertensão Essencial/epidemiologia , Hipertensão Essencial/genética , Feminino , Frequência do Gene , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Diabetes Metab Syndr ; 13(2): 1317-1320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336484

RESUMO

BACKGROUND: Essential hypertension is an important risk factor for the development of cardiovascular disease. Important candidate genes such as NOS3 gene have been widely studied and reported to be associated with essential hypertension (HTN) in human populations. AIM: We aim in this study to analyze the relationship between NOS3 -786T/C, a common genetic variant and HTN in a sample of the Algerian population of the Oran city. METHODS: A case-control study has been performed in 154 subjects including 77 hypertensives and 77 normotensives. The recruitment of these subjects was done in local Health Centers of the city of Oran, West Algeria. HTN was defined as elevated systolic blood pressure SBD≥140  mmHg and or sustained diastolic blood pressure DBP≥90  mmHg, measured using an Omron® Automatic BP Monitor - M-3W machine. Consents were obtained from all participants. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to genotype the NOS -786T/C variant. RESULTS: The distribution of the allelic frequencies did not differ between cases and controls (OR = 1.48; 95%CI [0.94-2.32], P = 0.09). However, after adjustment with the age, sex, and body mass index, we observed significant association between NOS -786C allele and HTN status (OR = 2.08; 95%CI [1.18-3.66], P = 0.01). CONCLUSION: Our results indicate that the C allele of the NOS3 gene is associated with increased risk of essential hypertension in this sample of the Algerian population of the Oran city. Further validation in larger samples is needed to confirm this finding.


Assuntos
Biomarcadores/análise , Hipertensão Essencial/epidemiologia , Hipertensão Essencial/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Adulto , Argélia/epidemiologia , Estudos de Casos e Controles , Hipertensão Essencial/patologia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
19.
BMC Med Genet ; 20(1): 121, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277597

RESUMO

BACKGROUND: The mitochondrial genotype 5178 cytosine/adenine (5178 C > A) within the NADH dehydrogenase subunit-2 gene (ND2) was proved to associate with longevity and predispose resistance to adult-onset diseases. This study aimed to confirm the interactive effects between ND 25178 C > A and clinical risk factors on the susceptibility of essential hypertension in Chinese general population. MATERIALS AND METHODS: The relationship between the ND2 5178 C > A variation and the risk of hypertension was investigated in 817 hypertensives and 821 matched normotensives. The interactive effects between ND2 5178 C > A and clinical risk factors were evaluated. RESULTS: The ND2 5178 A allele was more frequent in normotensives than in hypertensives (32.64% vs. 24.24%; adjusted OR: 0.62, 95% CI: 0.49-0.79, P = 1.3 × 10- 4). After stratification, the significant association between ND2 5178 C > A and hypertension was found only in current smokers (OR: 0.44, 95% CI: 0.31-0.62), but not in non-current smokers (p <  0.01 for interaction). Smoking status (OR: 1.51, 95% CI: 1.11-2.06) and high triglycerides (OR: 1.57, 95% CI: 1.10-2.24) were found independently associated with hypertension only in carriers of 5178 C allele but not in carriers of 5178 A allele. CONCLUSIONS: In conclusion, ND2 5178 A allele could confer a lower risk for essential hypertension in Chinese by the interaction with smoking status. The higher risk of hypertension imposed by smoking and high TG may be altered by ND2 5178 A allele.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipertensão Essencial/genética , Predisposição Genética para Doença/genética , Mitocôndrias/genética , NADH Desidrogenase/genética , Adulto , Alelos , Pressão Sanguínea , Feminino , Estudos de Associação Genética , Variação Genética , Genótipo , Humanos , Longevidade/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos
20.
Hypertension ; 74(2): 359-367, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31230554

RESUMO

Patients affected by primary aldosteronism (PA) display an increased risk of cardiovascular events compared with essential hypertension (EH). Endothelial dysfunction favors initiation and progression of atherosclerosis and circulating extracellular vesicles (EVs), reflecting endothelial cell activity, could represent one of the mediators of endothelial dysfunction in these patients. The aim of this study was to characterize circulating EVs from patients diagnosed with PA and to explore their functional significance. Serum EVs were isolated from 12 patients with PA and 12 with EH, matched by sex, age, and blood pressure, and compared with 8 normotensive controls. At nanoparticle tracking analysis, EVs concentration was 2.2× higher in patients with PA ( P=0.033) compared with EH and a significant correlation between EV number and serum aldosterone and potassium levels was identified. Fluorescence-activated cell sorting analysis demonstrated that patients with PA presented a higher absolute number of endothelial-derived EVs compared with both patients with EH and normotensive controls. Through EV mRNA profiling, 15 up-regulated and 4 down-regulated genes in patients with PA compared with EH were identified; moreover, EDN1 was expressed only in patients with PA. Microarray platform was validated by quantative real-time polymerase chain reaction on 4 genes ( CASP1, EDN1, F2R, and HMOX1) involved in apoptosis, inflammation, and endothelial dysfunction. After unilateral adrenalectomy, EVs number and expression of CASP1 and EDN1 significantly decreased in patients with PA ( P<0.05). Additionally, the incubation with PA-derived EVs reduced angiogenesis and induced apoptosis in vitro. Circulating EVs might not only represent a marker of endothelial dysfunction but also contribute themselves to vascular dysfunction in patients with PA.


Assuntos
Hipertensão Essencial/fisiopatologia , Vesículas Extracelulares/genética , Regulação da Expressão Gênica/genética , Hiperaldosteronismo/genética , Neovascularização Patológica/genética , Adulto , Apoptose/genética , Estudos de Casos e Controles , Células Cultivadas , Hipertensão Essencial/genética , Feminino , Humanos , Hiperaldosteronismo/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência
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