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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.
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
5.
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
6.
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.

7.
J Investig Med ; 64(7): 1194-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27430242

RESUMO

UNLABELLED: The purpose of this study was to assess the effects of 12 weeks of atorvastatin treatment on myocardial fibrosis in patients with hypertension with atherosclerosis. 15 statin-naïve participants (11 males; mean age 67±10 years) with atherosclerosis were given atorvastatin (40 mg/day) for 12 weeks and underwent echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS). Serum galectin-3 and fibrosis markers including aminoterminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also analyzed. After 12 weeks of atorvastatin (40 mg/day) treatment, serum total cholesterol and low-density lipoprotein cholesterol decreased significantly (204±31 to 140±24 mg/dL and 133±26 to 69±17 ng/mL, respectively, both p<0.001). In myocardial fibrosis analysis, CVIBS increased significantly (6.6±1.9 to 8.5±2.7 dB, p=0.024). In addition, the circulating fibrosis markers serum PIIINP and TIMP-1 decreased significantly (9.5±2.7 to 6.4±1.4 ng/mL, p=0.012 and 299±65 to 250±45 ng/mL, p=0.024, respectively). 12 weeks of medium dose atorvastatin treatment resulted in a significant reduction in myocardial fibrosis as evaluated by morphofunctional parameters and plasma markers of tissue fibrosis. TRIAL REGISTRATION NUMBER: NTC00172419; results.


Assuntos
Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Atorvastatina/uso terapêutico , Biomarcadores/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Miocárdio/patologia , Idoso , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Eletrocardiografia , Feminino , Fibrose , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Masculino
8.
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
9.
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
10.
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
11.
J Clin Endocrinol Metab ; 100(11): 4339-47, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26401591

RESUMO

CONTEXT: The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA). OBJECTIVE: Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. DESIGN: We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells. SETTING: This study took place in an academic clinical research center. PARTICIPANTS: Participants included 35 patients with PA and 30 patients with EH. INTERVENTIONS: Adrenalectomy was undertaken in patients with aldosterone-producing adenoma. RESULTS: The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2. CONCLUSIONS: Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.


Assuntos
Aldosterona/farmacologia , Hiperaldosteronismo/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adrenalectomia , Adulto , Pressão Sanguínea , Células Cultivadas , Feminino , Humanos , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Nitratos/farmacologia , Estudos Prospectivos , Interferência de RNA , RNA Mensageiro/biossíntese , Receptores de Mineralocorticoides/efeitos dos fármacos , Receptores de Mineralocorticoides/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Resultado do Tratamento
12.
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
13.
J Hypertens ; 33(9): 1922-30; discussion 1930, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103125

RESUMO

OBJECTIVE: To test if collagen markers are associated with aldosterone-induced diastolic dysfunction. BACKGROUND: Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction. METHODS: We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group. RESULTS: The baseline plasma TIMP-1 level (88.4 ±â€Š38.7 vs. 63.6 ±â€Š32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ±â€Š2.9 vs. 9.0 ±â€Š2.1; P < 0.001) were significantly higher in the APA group. The baseline plasma TIMP-1 level significantly correlated with the E/E' ratio, LVMI, interventricular septum, and left atrial diameter. The plasma MMP-2 level did not correlate with the left ventricular structure parameters, except for interventricular septum thickness. After adrenalectomy, LVMI and E/E' ratio improved significantly. The postadrenalectomy plasma TIMP-1 levels, but not MMP-2 levels, also decreased. The change of plasma TIMP-1 levels was negatively associated with the postadrenalectomy E/E' ratio after adjustment for age, sex, BMI, and mean blood pressure (ß-coefficient = - 3.6, P = 0.004). CONCLUSION: Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction.


Assuntos
Neoplasias do Córtex Suprarrenal/sangue , Adenoma Adrenocortical/sangue , Ventrículos do Coração/diagnóstico por imagem , Hiperaldosteronismo/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/complicações , Adenoma Adrenocortical/cirurgia , Adulto , Aldosterona/sangue , Diástole , Ecocardiografia Doppler , Hipertensão Essencial , Feminino , Humanos , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/cirurgia , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Hipertensão/patologia , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Resultado do Tratamento
14.
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
15.
J Renin Angiotensin Aldosterone Syst ; 16(2): 353-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25143326

RESUMO

INTRODUCTION: Hypokalemia in primary aldosteronism (PA) patients correlates with higher levels of cardiovascular events and altered left ventricular geometry. However, the influence of aldosterone on microvascular endothelial function and the effect of hypokalemia on the vascular structure still remain unclear. OBJECTIVES: We investigated the peripheral arterial functions, including the endothelial function of microvasculature and arterial stiffness in PA and essential hypertension (EH) patients, and the correlation between hypokalemia and peripheral arterial function among PA patients. METHODS: Twenty patients diagnosed as EH and 37 patients with PA were enrolled in this study. Reactive hyperemia index (RHI) and the augmentation index (AI) were obtained by non-invasive peripheral arterial tonometry. RESULTS: Twenty EH patients and a total of 37 PA patients, including 21 patients with normokalemia and 16 patients with hypokalemia, were enrolled and divided into groups 1, 2 and 3 respectively. PA patients had significantly higher AI (p=0.024) but not RHI than EH patients. RHI showed no difference between groups 1, 2 and 3. Group 3 had higher AI than either group 1 or group 2. In the whole study population, serum potassium level, after multivariate regression analysis testing, was the only factor associated with AI (ß= -0.102; p=0.002). In PA patients, serum potassium level was the only significant factor correlated with AI. (r= -0.458; p=0.004) CONCLUSIONS: PA patients had higher arterial stiffness but comparable microvascular endothelial function to EH patients. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in PA patients.


Assuntos
Endotélio Vascular/fisiopatologia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/fisiopatologia , Hipopotassemia/complicações , Hipopotassemia/fisiopatologia , Microvasos/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão
16.
PLoS One ; 9(9): e95254, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25180794

RESUMO

CONTEXT: Patients with primary aldosteronism are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis. OBJECTIVE: To investigate whether aldosterone induces galectin-3 secretion in vitro and in vivo. METHODS AND RESULTS: We investigated the possible molecular mechanism of aldosterone-induced galectin-3 secretion in macrophage cell lines (THP-1 and RAW 264.7 cells). Aldosterone induced galectin-3 secretion through mineralocorticoid receptors via the PI3K/Akt and NF-κB transcription signaling pathways. In addition, aldosterone-induced galectin-3 expression enhanced fibrosis-related factor expression in fibroblasts. We observed that galectin-3 mRNA from peripheral blood mononuclear cells and serum galectin-3 levels were both significantly increased in mice implanted with aldosterone pellets on days 7 and 14. We then conducted a prospective preliminary clinical study to investigate the association between aldosterone and galectin-3. Patients with aldosterone-producing adenoma had a significantly higher plasma galectin-3 level than patients with essential hypertension. One year after adrenalectomy, the plasma galectin-3 level had decreased significantly in the patients with aldosterone-producing adenoma. CONCLUSION: This study demonstrated that aldosterone could induce galectin-3 secretion in vitro and in vivo.


Assuntos
Aldosterona/farmacologia , Galectina 3/metabolismo , Adrenalectomia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose , Galectina 3/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Hiperaldosteronismo/cirurgia , Masculino , Camundongos , Miocárdio/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
17.
Int J Med Sci ; 11(11): 1098-106, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25170292

RESUMO

BACKGROUND: Galectin-3 (Gal-3) shows the ability of survival prediction in heart failure (HF) patients. However, Gal-3 is strongly associated with serum markers of cardiac extracellular matrix (ECM) turnover. The aim of this study is to compare the impact of Gal-3 and serum markers of cardiac ECM turnover on prognostic prediction of chronic systolic HF patients. METHODS: Serum Gal-3, brain natriuretic peptide (BNP), extracellular matrix including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2, 9 (MMP-2, 9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. Cox regression analysis was used for survival analysis. RESULTS: A total of 105 (81 male) patients were enrolled. During 980±346 days follow-up, 17 patients died and 36 episodes of HF admission happened. Mortality of these patients was significantly associated with the log PIIINP (ß= 15.380; P=0.042), log TIMP-1(ß= 44.530; P=0.003), log MMP-2 (ß= 554.336; P<0.001), log BNP (ß= 28.273; P=0.034). Log Gal-3 (ß= 7.484; P=0.066) is borderline associated with mortality. Mortality or first HF admission of these patients was significantly associated with the log TIMP-1(ß= 16.496; P=0.006), log MMP-2 (ß= 221.864; P<0.001), log BNP (ß= 5.999; P=0.034). Log Gal-3 (ß= 4.486; P=0.095) only showed borderline significance. In several models adjusting clinical parameters, log MMP-2 was significantly associated with clinical outcome. In contrast, log Gal-3 was not. CONCLUSION: The prognostic strength of MMP-2 to clinical outcome prediction in HF patients is stronger than Gal-3.


Assuntos
Galectina 3/sangue , Insuficiência Cardíaca Sistólica/sangue , Insuficiência Cardíaca Sistólica/patologia , Idoso , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Pró-Colágeno/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue
18.
Clin Biochem ; 47(13-14): 1329-32, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24892901

RESUMO

OBJECTIVE: To investigate the association between aldosterone and cardiac diastolic dysfunction. DESIGN AND METHODS: We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. RESULTS: PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. CONCLUSIONS: Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function.


Assuntos
Aldosterona/urina , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/urina , Hipertensão/fisiopatologia , Hipertensão/urina , Função Ventricular Esquerda/fisiologia , Adulto , Aldosterona/sangue , Ecocardiografia/métodos , Hipertensão Essencial , Feminino , Humanos , Hiperaldosteronismo/sangue , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/urina
19.
Clin Biochem ; 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23376327

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

20.
ScientificWorldJournal ; 2013: 294594, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24459427

RESUMO

OBJECTIVE: Primary aldosteronism (PA) is associated with inappropriate left ventricular hypertrophy (LVH) in relation to a given gender and body size. There is no ideal parameter to predict the presence of LVH or inappropriate LVH in patients with PA. We investigate the performance of 24-hour urinary aldosterone level, plasma renin activity and aldosterone-to-renin ratio on this task. METHODS: We performed echocardiography in 106 patients with PA and 31 subjects with essential hypertension (EH) in a tertiary teaching hospital. Plasma renin activity, aldosterone concentration, and 24-hour urinary aldosterone level were measured. RESULTS: Only 24-hour urinary aldosterone was correlated with left ventricular mass index (LVMI) and excess LVMI among these parameters. The multivariate analysis revealed the urinary aldosterone level as an independent predictor for LVMI and excess LVMI. Analyzing the ability of urinary aldosterone, plasma aldosterone concentration, and plasma aldosterone-to-renin ratio to identify the presence of LVH (ROC AUC = 0.701, 0.568, 0.656, resp.) and the presence of inappropriate LV mass index (defined as measured LVMI in predicting LVMI ratio >135%) (ROC area under curve = 0.61, 0.43, 0.493, resp.) revealed the better performance of 24-hour urinary aldosterone. CONCLUSIONS: In conclusion, 24-hour urinary aldosterone level performed better to predict the presence of LVH and inappropriate LVMI in patients with PA.


Assuntos
Aldosterona/urina , Tamanho Corporal , Hiperaldosteronismo/urina , Hipertrofia Ventricular Esquerda/urina , Caracteres Sexuais , Idoso , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Renina/sangue , Fatores Sexuais
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