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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165627, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785407

RESUMO

Macrophages play an important role in aldosterone-induced myocardial fibrosis, in which the first key steps are macrophage recruitment and infiltration. We hypothesized that IL-6 may be a key mediator of aldosterone-induced macrophage recruitment and infiltration. To test this hypothesis, we designed cell studies with a human monocytic cell line THP-1 that with monocyte/macrophage functions to explore the signaling pathway of aldosterone-induced macrophage infiltration, and further investigated the phenomenon and consequent pathway in aldosterone-infused mice studies. The results showed that aldosterone induced the expression of IL-6 via mineralocorticoid receptors, and enhanced THP-1 cell migration and infiltration. Further experiments using a protease array and siRNA revealed that expressions of MMP-1 and MMP-9 were associated with aldosterone-induced macrophage infiltration. In addition, aldosterone-induced MMP-1 and MMP-9 expressions were mediated via cyclooxygenase-II and prostaglandin E2/EP-2 and EP-4 receptors. In aldosterone-infused mice, mRNA expressions of MMP-1, MMP-9 and COX-2 in peripheral blood monocytic cells were significantly increased. Moreover, the number of mouse macrophage-restricted F4/80 protein-positive cells in the myocardium was significantly higher in the aldosterone-infused mice compared with control mice. The increase in F4/80-positive cells in the myocardium was suppressed in the aldosterone-infused mice with the aldosterone antagonist eplerenone or anti-IL-6 antibody treatment. In conclusion, interleukin-6 played an important role in aldosterone-induced macrophage recruitment and infiltration in the myocardium.

2.
J Investig Med ; 68(2): 371-377, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31630138

RESUMO

Estimated glomerular filtration rate (eGFR) is an important topic in patients with primary aldosteronism (PA). However, the relationship between left ventricular structure and eGFR is unclear. We conducted a prospective, observational, and cross-sectional study to analyze 168 patients with PA and 168 propensity score-matched patients with essential hypertension (EH) as the control group, matched by age, gender, and systolic blood pressure. In the patients with PA, the eGFR was not correlated with left ventricular mass index (LVMI; r=-0.065, p=0.404), while in the patients with EH, the eGFR was negatively correlated with LVMI (r=-0.309, p<0.001). To test whether eGFR had a non-linear relationship with LVMI among the patients with PA, we stratified the patients with PA according to the tertile of eGFR (low, medium, and high tertile). The medium tertile of patients had a significantly lower LVMI than those in the other two tertiles (LVMI: 143.5±41.6, 120.5±40.5, and 133.1±34.3 g/m2, from the lowest to highest tertile of eGFR; analysis of covariance p=0.032). The medium tertile of eGFR is associated with lowest LVMI. Patients with PA with high and low eGFR were associated with higher LVMI. The findings implied that the reasons for an increased LVMI in patients with PA may be different to those in patients with EH.

3.
J Am Heart Assoc ; 8(22): e013263, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31718437

RESUMO

Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone-producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone-producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone-producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e' (P<0.001) and higher E/e' (P=0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age (P<0.001), sex (P<0.001), body mass index (P=0.002), systolic blood pressure (P=0.004), creatinine (P=0.008), and log-transformed aldosterone-renin ratio (P=0.003). After adrenalectomy, the patients with aldosterone-producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e' (P=0.003) and decrease in E/e' (P=0.002). The change in E/e' was independently correlated with baseline E/e' (P<0.001) and change in LV mass index (P=0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

4.
Int J Mol Sci ; 20(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640178

RESUMO

Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.

5.
Hypertension ; 74(3): 623-629, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31352825

RESUMO

Primary aldosteronism (PA) is hemodynamically independently associated with arterial wall stiffness as assessed by pulse wave velocity (PWV) compared with essential hypertension. Arterial wave reflection parameters derived from pulse wave analysis, such as forward and backward wave amplitudes (Pf and Pb), are promising vascular markers to predict cardiovascular outcomes in addition to PWV. These vascular parameters have never been studied in patients with PA before. In study part A, we prospectively enrolled 67 patients with PA and 132 patients with essential hypertension. In study part B, another 54 patients with PA were enrolled. Heart-carotid PWV was measured, and carotid pressure waveforms were recorded to calculate Pf, Pb, and augmentation index at baseline (part A and B) and 6 months after treatment (part B). The results showed that the patients with PA had significantly higher Pf (P=0.001), Pb (P=0.01), and PWV (P=0.021) than the patients with essential hypertension. In univariate correlation analysis, both log Pf and Pb were significantly correlated with age, office blood pressure, serum potassium level, log PWV, and the presence of PA. However, only Pb was significantly correlated with log plasma renin activity and log aldosterone to renin ratio. In multivariate analysis, log Pf was significantly correlated with the presence of PA (P=0.001), male sex, age, and mean arterial blood pressure. Pb was significantly correlated with the presence of PA (P=0.031), age, and mean arterial pressure. Six months after treatment, Pf and Pb decreased significantly. In conclusion, the patients with PA had significantly increased wave reflections compared with the patients with essential hypertension. Our results provide clinical evidence of aldosterone-related extensive vascular dysfunction of the arterial system.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/tratamento farmacológico , Hiperaldosteronismo/complicações , Hipertensão/tratamento farmacológico , Adulto , Aldosterona/sangue , Anti-Hipertensivos/farmacologia , Área Sob a Curva , Pressão Arterial/efeitos dos fármacos , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Medição de Risco , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto Jovem
6.
Appl Bionics Biomech ; 2019: 7987496, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178925

RESUMO

X-ray radiography is currently used in dentistry and can be divided into two categories: two-dimensional (2D) radiographic images (e.g., using periapical film, cephalometric film, and panoramic X-ray) and three-dimensional (3D) radiographic images (e.g., using dental cone-beam computed tomography (CBCT)). Among them, 2D periapical film images are most commonly used. However, 2D periapical film compresses 3D image information into a 2D image, which means that depth cannot be identified from the image. Such compressed images lose a considerable amount of information, reducing their clinical applicability. A 2.5D periapical radiography system prototype was developed by our research team. Our previous study indicated that this prototype could be used to capture images at different depths of an object. However, the prototype was limited by its commercially available intraoral periapical sensor, which had a low temporal resolution and could not capture multiple images in a short period of time. Therefore, the total time required for image capture was too long for practical clinical application. The present study developed a high-frame-rate intraoral periapical sensor with a sensor imaging speed of up to 15 Hz. The primary components of the developed intraoral periapical sensor include a scintillator, complementary metal oxide semiconductor chip, component circuit board, and video processing board. The external dimensions of the sensor are 41 × 26 × 6.6 mm3. The performance of the developed high-frame-rate intraoral periapical sensor was verified through qualified and quantified analyses using line pairs. The results showed that the resolution of the developed intraoral periapical sensor could reach 18 lp/mm. The sensor was further installed in our 2.5D periapical radiography system to conduct image capturing. The results indicated that the developed sensor could be used for high-frame-rate imaging to incorporate tomosynthesis to obtain reconstructed slice images of different depths. The developed sensor has the potential for clinical dentistry applications in the future.

7.
PLoS One ; 13(12): e0209698, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586444

RESUMO

This study used available or purchased equipment and an image reconstruction system developed by the college of dentistry to establish a basic self-assembled micro-computed tomography (micro-CT) system. Such a system would be suitable for teaching dental radiology to dental students. Specifically, it could help students to understand the principles governing dental cone-beam computed tomography (CBCT) and provide graduate students with a system for scanning small samples (e.g., individual teeth) during the early stages of research. The self-assembled micro-CT system was constructed using a portable dental X-ray tube, an intraoral digital X-ray detector, a high-precision rotation stage, related bracket accessories, and a notebook computer. Reconstructed images and three-dimensional models of the maxillary right third molar were produced using the self-assembled micro-CT system and an advanced commercially available micro-CT system (Skyscan 2211). Subsequently, the reconstructed images and 3D models produced using the two systems were compared by two senior dentists to determine whether considerable visual differences could be observed. Finally, the signal-to-noise ratio (SNR) was used for quantitative analysis and to compare the systems. Although the self-assembled micro-CT system produced image boundaries that were not as sharp as those of Skyscan 2211, the images were nonetheless remarkably similar. In addition, the two micro-CT systems produced 3D models that were almost identical in appearance and root canal shape. Quantitative analysis revealed that Skyscan 2211 had produced a SNR that was superior to that of the self-assembled micro-CT system, with the difference ranging from 36.77% to 136.22%; enamel, which has a higher density, exhibited lower SNR differences, whereas dentin, which has a lower density, exhibited higher SNR differences. The self-assembled micro-CT system with a resolution of 36 µm was created using a portable dental X-ray tube and an intraoral digital X-ray detector. Although the scanning time was relatively long (~30 min to scan images of a tooth), the images were adequate in the preliminary stage of experiments. More importantly, students were afforded the opportunity to observe the process of assembling and disassembling each component of a micro-CT scanner and thereby achieve a more comprehensive understanding of the principles governing micro-CT and dental CBCT.


Assuntos
Educação em Odontologia , Mandíbula/diagnóstico por imagem , Dente/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Humanos , Processamento de Imagem Assistida por Computador , Imagem Tridimensional/métodos , Radiografia Dentária/métodos
8.
Cardiovasc Res ; 114(5): 690-702, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29360942

RESUMO

Aims: An excess of aldosterone results in cardiac remodelling and fibrosis. Interleukin-6 (IL-6) is a key mediator in the fibrotic process; however, the effect of aldosterone on the expression of IL-6 remains unclear. We investigated whether aldosterone induces the expression of IL-6 and thereby contributes to the fibrotic process. Methods and results: In this clinical study, we prospectively enrolled 25 patients with primary aldosteronism (PA) and 26 patients with essential hypertension (EH). The PA patients had higher plasma IL-6 levels, left ventricular mass index, degree of myocardial fibrosis, and more impaired diastolic function than the EH patients. In addition, plasma IL-6 levels were positively correlated with 24-h urinary aldosterone and echocardiographic parameters. In cell studies, we investigated the possible molecular mechanism how aldosterone-induced IL-6 secretion and the further effects of collagen production. Aldosterone significantly induced IL-6 protein and mRNA production in human umbilical vein endothelial cells. Intracellular signalling occurred through the mineralocorticoid receptor/PI3K/Akt/NF-kB pathway. In cardiac fibroblasts, IL-6 trans-signalling played a critical role in aldosterone-induced IL-6-enhanced fibrosis-related factor expression. To further investigate the role of IL-6 trans-signalling in aldosterone-induced cardiac fibrosis, we measured the severity of myocardial fibrosis in aldosterone infusion mice models including an IL-6 chemical inhibitor and Sgp130 Knockin Transgenic Mice. Mice receiving recombinant soluble gp130 and Sgp130 Knockin Transgenic Mice prevented myocardial fibrosis and cardiac hypertrophy by aldosterone infusion. Conclusions: IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.


Assuntos
Aldosterona/metabolismo , Cardiomegalia/metabolismo , Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hiperaldosteronismo/metabolismo , Interleucina-6/metabolismo , Miocárdio/metabolismo , Remodelação Ventricular , Adulto , Aldosterona/farmacologia , Animais , Cardiomegalia/etiologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Colágeno/metabolismo , Receptor gp130 de Citocina/genética , Receptor gp130 de Citocina/metabolismo , Hipertensão Essencial/etiologia , Hipertensão Essencial/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibrose , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hiperaldosteronismo/complicações , Interleucina-6/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Miocárdio/patologia , Estudos Prospectivos , Receptores de Mineralocorticoides/metabolismo , Transdução de Sinais
9.
J Hypertens ; 36(2): 353-360, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28902663

RESUMO

BACKGROUND: Primary aldosteronism is associated with a higher incidence of left ventricular (LV) hypertrophy and diastolic dysfunction than essential hypertension. However, systolic function via endocardial measurements is similar between patients with primary aldosteronism and essential hypertension. Speckle-tracking echocardiography is a sensitive tool which can detect subclinical impairments in systolic function. The aim of this study was to investigate aldosterone-induced subclinical impairments in systolic function. METHODS: We prospectively enrolled patients with primary aldosteronism and essential hypertension and analyzed their clinical data, biochemical data, and echocardiographic parameters, including myocardial strain [global longitudinal strain (GLS)]. RESULTS: Thirty-six patients with primary aldosteronism and 31 patients with essential hypertension were enrolled for analysis. The patients with primary aldosteronism had significantly lower serum potassium levels, lower plasma renin activity, higher aldosterone-to-renin ratio (ARR), and higher 24-h urinary aldosterone levels than patients with essential hypertension. With regards to echocardiographic parameters, the patients with primary aldosteronism had a thicker ventricular wall and higher LV mass index than those with essential hypertension. Most importantly, we found significant degradation of GLS in the patients with primary aldosteronism compared with those with essential hypertension (-17.84 ±â€Š2.36 vs. -20.13 ±â€Š2.32, P < 0.001). In correlation analysis, GLS was significantly correlated with serum potassium level, LV mass index, log-transformed plasma renin activity, log-transformed ARR, and log-transformed 24-h urinary aldosterone levels (all P < 0.05). Multivariate linear regression analysis further identified log-transformed ARR (ß = 0.771, 95% confidence interval: 0.011-1.530, P = 0.047), and log-transformed 24-h urinary aldosterone level (ß = 1.765, 95% confidence interval: 0.01-3.529, P = 0.050) as independent factors correlated with GLS. CONCLUSION: Patients with primary aldosteronism have a lower magnitude of GLS than patients with essential hypertension, suggesting that aldosterone induces a subclinical decline in LV systolic function.


Assuntos
Aldosterona/sangue , Hipertensão Essencial/fisiopatologia , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Aldosterona/urina , Ecocardiografia/métodos , Hipertensão Essencial/sangue , Hipertensão Essencial/diagnóstico por imagem , Feminino , Coração/fisiopatologia , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hipertensão , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miocárdio , Potássio/sangue , Estudos Prospectivos , Renina/sangue , Sístole , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
10.
Oncotarget ; 8(42): 73187-73197, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069862

RESUMO

Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa (low, median, and high tertile). PA patients with medium tertile of UNa had significant lower LVMI than the other two groups (LVMI: 144.1 ± 42.9, 121.1 ± 33.4, and 136.7 ± 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of variance p=0.006, post-hoc p <0.05). Multifactor analysis of variance confirmed this finding after adjustment for clinical parameters. Post-hoc analyses revealed that the high UNa tertile was associated with higher left ventricular end-diastolic volume compared with medium UNa tertile; while the low UNa tertile was associated with higher mean wall thickness compared with medium UNa tertile. The findings imply the reasons for increased LVMI may be different in patients with the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour UNa is associated with lowest LVMI in patients with PA.

11.
J Investig Med ; 64(6): 1109-13, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27190071

RESUMO

UNLABELLED: Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy. TRIAL REGISTRATION NUMBER: 200611031R; Results.


Assuntos
Aldosterona/metabolismo , Galectina 3/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Adrenalectomia , Eletrocardiografia , Feminino , Fibrose , Seguimentos , Galectina 3/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
12.
Sci Rep ; 6: 23838, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27032984

RESUMO

Extra-corporeal membranous oxygenation (ECMO) has been applied in patients with cardiopulmonary failure. One critical drawback of peripheral ECMO is an increase in left ventricular (LV) afterload which could be counterbalanced by the combination of intra-aortic balloon counter-pulsation (IABP) therapy. We hypothesized that an add-on therapy with IABP could improve outcomes in patients receiving ECMO support. We included patients (>18 years old) from 2002 to 2013 requiring ECMO support due to cardiogenic shock in a medical center. A total of 529 patients (227 ECMO alone and 302 combined IABP plus ECMO) were included. The mortality rates at 2 weeks (48.5 vs. 47.7%) after ECMO implantation were not different between the two groups (ECMO vs. combined group). After adjustment for propensity score and potential confounders, the odds ratios of outcomes within 14 days (combined group vs. ECMO) for poor LV systolic function, high preload, multi-organ failure and mortality were not different. The results remained similar for subgroup analysis. Compared with ECMO alone, combined IABP and ECMO treatment did not improve outcomes in patients with circulatory failure.


Assuntos
Cuidados Críticos/métodos , Oxigenação por Membrana Extracorpórea , Balão Intra-Aórtico , Choque Cardiogênico/terapia , Adulto , Idoso , Feminino , Humanos , Balão Intra-Aórtico/métodos , Masculino , Pessoa de Meia-Idade , Choque Cardiogênico/mortalidade , Sístole , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia
13.
Hypertension ; 67(6): 1309-20, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27113051

RESUMO

Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity.


Assuntos
Colágeno/metabolismo , Hiperaldosteronismo/fisiopatologia , Metaloproteinase 1 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Aldosterona/metabolismo , Análise de Variância , Animais , Biópsia por Agulha , Western Blotting , Modelos Animais de Doenças , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibrose/genética , Fibrose/patologia , Regulação da Expressão Gênica , Humanos , Hiperaldosteronismo/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , RNA Mensageiro/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transdução de Sinais
14.
Sci Rep ; 6: 20862, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26883298

RESUMO

Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (ΔDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors.


Assuntos
Adenoma/complicações , Adenoma/metabolismo , Aldosterona/biossíntese , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Rigidez Vascular , Adenoma/diagnóstico , Adenoma/cirurgia , Adrenalectomia , Adulto , Índice Tornozelo-Braço , Feminino , Hemodinâmica , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Resultado do Tratamento , Doenças Vasculares/fisiopatologia , Doenças Vasculares/terapia
15.
J Investig Med ; 63(6): 816-20, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26083251

RESUMO

BACKGROUND: Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. METHODS: We prospectively analyzed 30 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. RESULTS: Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (ß = -0.287, P = 0.049), ΔSBP (ß = 0.518, P = 0.01), and Δserum potassium level (ß = -20.471, P = 0.014) were significantly correlated with ΔLVMI. CONCLUSIONS: The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression.


Assuntos
Adrenalectomia , Ventrículos do Coração/patologia , Hiperaldosteronismo/sangue , Hiperaldosteronismo/cirurgia , Potássio/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tamanho do Órgão , Análise de Regressão , Resultado do Tratamento
16.
Int J Med Sci ; 12(5): 369-77, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26005371

RESUMO

BACKGROUND: Glomerular hyperfiltration has been recently noticed as an important issue in primary aldosteronism (PA) patients. However, its effect on the cardiovascular system remains unknown. METHODS: We prospectively analyzed 47 PA patients including 11 PA patients with estimated glomerular filtration rate (eGFR) > 130 ml/min per 1.73 m2 (group 1), and 36 PA patients with eGFR 90-110 ml/min per 1.73 m2 (group 2). Fourteen essential hypertension (EH) patients with eGFR 90-110 ml/min per 1.73 m2 were included as the control group (group 3). Echocardiography including left ventricular mass index (LVMI) measurement and tissue Doppler imaging (TDI) was performed. Predicted left ventricular mass (LVM) was calculated. Inappropriate LVM was defined as an excess of > 35% from the predicted value. RESULTS: The value of LVMI decreased significantly in order from groups 1 to 3 (group 1>2>3). While group 2 had a significantly higher percentage of inappropriate LVM than group 3, the percentage of inappropriate LVM were comparable in groups 1 and 2. Group 1 had a higher mitral E velocity, E/A ratio than that of group 2. In the TDI study, the E/E' ratio also decreased significantly in order from groups 1 to 3 (group 1>2>3). Group 2 had lower E' than that of group 3, although the E' of group 1 and 2 were comparable. CONCLUSIONS: Although PA patients with glomerular hyperfiltration were associated with higher LVMI, higher mitral E velocity, higher E/E' ratio, they had comparable E' with PA patients with normal GFR. This phenomenon may be explained by higher intravascular volume in this patient group.


Assuntos
Taxa de Filtração Glomerular , Ventrículos do Coração/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Adulto , Ecocardiografia , Hipertensão Essencial , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
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