Citrisorbicillinol, an undescribed hybrid sorbicillinoid with osteogenic activity from Penicillium citrinum ZY-2.

Citrisorbicillinol (1), along with six other known compounds (2-7), was isolated from an endphyte Penicillium citrinum ZY-2 of Plantago asiatica L. Citrisorbicillinol (1) was characterized as a skeletally unprecedented hybrid sorbicillinoid, and its unique framework is likely formed by intermolecular [4 + 2] cycloaddition between intermediates derived from citrinin and sorbicillinoid biosynthetic gene clusters. Compounds 1 and 2 demonstrated to promote osteoblastic differentiation in MC3T3-E1 cells, and to be osteogenic in the prednisolone induced osteoporotic zebrafish. Compounds 3-7 exhibited moderate cytotoxicity against four human cancer cell lines.

Anatomical and functional remodeling of left ventricle in patients with primary aldosteronism and concomitant albuminuria.

Background: Primary aldosteronism (PA) is the leading cause of secondary hypertension globally and is associated with adverse cardiovascular outcomes. However, the cardiac impact of concomitant albuminuria remains unknown. Objective: To compare anatomical and functional remodeling of left ventricle (LV) in PA patients with or without albuminuria. Design: Prospective cohort study. Methods: The cohort was separated into two arms according to the presence or absence of albuminuria (>30 mg/g of morning spot urine). Propensity score matching with age, sex, systolic blood pressure, and diabetes mellitus was performed. Multivariate analysis was conducted with adjustments for age, sex, body mass index, systolic blood pressure, duration of hypertension, smoking, diabetes mellitus, number of antihypertensive agents, and aldosterone level. A local-linear model with bandwidth of 2.07 was used to study correlations. Results: A total of 519 individuals with PA were enrolled in the study, of whom 152 had albuminuria. After matching, the albuminuria group had a higher creatinine level, at baseline. With regard to LV remodeling, albuminuria was independently associated with a significantly higher interventricular septum (1.22 > 1.17 cm, p = 0.030), LV posterior wall thickness (1.16 > 1.10 cm, p = 0.011), LV mass index (125 > 116 g/m2, p = 0.023), and medial E/e' ratio (13.61 > 12.30, p = 0.032), and a lower medial early diastolic peak velocity (5.70 < 6.36 cm/s, p = 0.016). Multivariate analysis further revealed that albuminuria was an independent risk factor for elevated LV mass index (p < 0.001) and medial E/e' ratio (p = 0.010). Non-parametric kernel regression also demonstrated that the level of albuminuria was positively correlated with LV mass index. The remodeling of LV mass and diastolic function under the presence of albuminuria distinctly improved after PA treatment. Conclusion: The presence of concomitant albuminuria in patients with PA was associated with pronounced LV hypertrophy and compromised LV diastolic function. These alterations were reversible after treatment for PA. Plain language summary: Cardiac Impact of Primary Aldosteronism and Albuminuria Primary aldosteronism and albuminuria has been, respectively, demonstrated to bring about left ventricular remodeling, but the aggregative effect was unknown. We constructed a prospective single-center cohort study in Taiwan. We proposed the presence of concomitant albuminuria was associated with left ventricular hypertrophy and compromised diastolic function. Intriguingly, management of primary aldosteronism was able to restore these alterations. Our study delineated the cardiorenal crosstalk in the setting of secondary hypertension and the role of albuminuria for left ventricular remodeling. Future interrogations toward the underlying pathophysiology as well as therapeutics will facilitate the improvement of holistic care for such population.

Aldosterone Suppresses Endothelial Mitochondria through Mineralocorticoid Receptor/Mitochondrial Reactive Oxygen Species Pathway.

Excessive aldosterone secretion causes endothelial dysfunction, vascular inflammation, and vascular fibrosis in patients with primary aldosteronism (PA). Endothelial function is closely related to endothelial mitochondria. However, the effects of elevated aldosterone levels on endothelial mitochondria remain unclear. In this study, we used primary cultured human umbilical vein endothelial cells (HUVECs) to investigate the effects of aldosterone on endothelial mitochondria. Mineralocorticoid receptor (MR) small interfering (si)RNA or glucocorticoid receptor (GR) siRNA were used to confirm the pathway by which aldosterone exerts its effects on the mitochondria of HUVECs. The results showed that excess aldosterone suppressed mitochondrial DNA copy numbers, anti-mitochondrial protein, and SOD2 protein expression in a dose- and time-dependent manner. These effects were attenuated by treatment with MR siRNA, but not with GR siRNA. Furthermore, it was attenuated by treatment with a mitochondria-targeted antioxidant (Mito-TEMPO, associated with mitochondrial reactive oxygen species (ROS) production), but not N-acetyl-L-cysteine (associated with cytosolic ROS production), which suggests that the process was through the mitochondrial ROS pathway, but not the cytosolic ROS pathway. In conclusion, aldosterone excess suppressed endothelial mitochondria through the MR/mitochondrial ROS pathway.

Three new polyketide derivatives of the endophytic fungus Aspergillus cristatus 2H1.

Three new polyketide derivatives, 2-ethoxycarbonyl-endocrocin (1), 6-methoxy-2-ethoxycarbonyl-endocrocin (2) and pannorin C (3), along with sixteen known compounds (4-19) were isolated from a plant endophytic fungus Aspergillus cristatus 2H1. Their structures were elucidated by 1D/2D NMR and HR-ESI-MS data analysis. Compound 3 showed weak antibacterial activity against Staphylococcus aureus (MIC 20 µg/ml). Compounds 14 and 15 showed effective cytotoxicity on human melanoma A375 cells (IC50 4.13 µM for 14, 3.39 µM for 15).

Aldosterone suppresses cardiac mitochondria.

Elevated serum aldosterone promotes arterial hypertension, cardiac hypertrophy, and diastolic dysfunction. However, the effect of elevated aldosterone levels on cardiac mitochondria remains unclear. We used primary cultures of mouse cardiomyocytes to determine whether aldosterone has direct effects on cardiomyocyte mitochondria, and aldosterone-infused mice as a preclinical model to evaluate the impact of aldosterone in vivo. We show that aldosterone suppressed mtDNA copy number and SOD2 expression via the mineralocorticoid receptor (MR)-dependent regulation of NADPH oxidase 2 (NOX2) and generation of reactive oxygen species (ROS) in primary mouse cardiomyocytes. Aldosterone suppressed cardiac mitochondria adenosine triphosphate production, which was rescued by N-acetylcysteine. Aldosterone infusion for 4 weeks in mice suppressed the number of cardiac mitochondria, mtDNA copy number, and SOD2 protein expression. MR blockade by eplerenone or the administration of N-acetylcysteine prevented aldosterone-induced cardiac mitochondrial damage in vivo. Similarly, patients with primary aldosteronism had a lower plasma leukocyte mtDNA copy number. Plasma leukocyte mtDNA copy number was positively correlated with 24-hour urinary aldosterone level and left ventricular mass index. In conclusion, aldosterone suppresses cardiac mitochondria in vivo and directly via MR activation of ROS pathways.

Regeneration of Phytochemicals by Structure-Driven Organization of Microbial Biosynthetic Steps.

Medicinal phytochemicals, such as artemisinin and taxol, have impacted the world, and hypericin might do so if its availability issue could be addressed. Hypericin is the hallmark component of Saint John's wort (Hypericum perforatum L.), an approved depression alleviator documented in the US, European, and British pharmacopoeias with its additional effectiveness against diverse cancers and viruses. However, the academia-to-industry transition of hypericin remain hampered by its low in planta abundance, unfeasible bulk chemical synthesis, and unclear biosynthetic mechanism. Here, we present a strategy consisting of the hypericin-structure-centered modification and reorganization of microbial biosynthetic steps in the repurposed cells that have been tamed to enable the designed consecutive reactions to afford hypericin (43.1 mg L-1 ), without acquiring its biosynthetic knowledge in native plants. The study provides a synthetic biology route to hypericin and establishes a platform for biosustainable access to medicinal phytochemicals.

Hemodynamic and Non-Hemodynamic Components of Cardiac Remodeling in Primary Aldosteronism.

Objectives: Patients with primary aldosteronism (PA) have cardiac remodeling due to hemodynamic and non-hemodynamic causes. However, component analysis of cardiac remodeling and reversal in PA patients is lacking. We investigated components of cardiac remodeling and reversal after adrenalectomy in patients with aldosterone-producing adenoma (APA). Methods: This study prospectively enrolled 304 APA patients who received adrenalectomy and 271 with essential hypertension (EH). Clinical, biochemical and echocardiographic data were collected in both groups and 1 year after surgery in the APA patients. The hemodynamic and non-hemodynamic components of left ventricular (LV) remodeling were represented by predicted left ventricular mass index (LVMI) (pLVMI) and inappropriately excessive LVMI (ieLVMI, defined as LVMI-pLVMI). Results: After propensity score matching, 213 APA and 213 EH patients were selected. APA patients had higher hemodynamic (pLVMI) and non-hemodynamic (ieLVMI) components of LV remodeling than EH patients. In multivariate analysis, baseline pLVMI was correlated with systolic blood pressure (SBP) and serum potassium, whereas ieLVMI was correlated with log plasma aldosterone concentration but not blood pressure. Post-operative echocardiography was available in 207 patents and showed significant decreases in both pLVMI and ieLVMI after adrenalectomy. In multivariate analysis, ΔpLVMI was correlated with SBP, ΔSBP, and pre-operative pLVMI, whereas ΔieLVMI was correlated with Δlog aldosterone-to-renin ratio (ARR) and pre-operative ieLVMI. Conclusions: This study concluded that extensive cardiac remodeling in APA patients occurs through hemodynamic and non-hemodynamic causes. Adrenalectomy can improve both hemodynamic and non-hemodynamic components of LV remodeling. Regressions of pLVMI and ieLVMI were correlated with decreases in blood pressure and ARR, respectively.

Interleukin-6 plays a critical role in aldosterone-induced macrophage recruitment and infiltration in the myocardium.

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.

IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.

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.

The relation among aldosterone, galectin-3, and myocardial fibrosis: a prospective clinical pilot follow-up study.

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.

Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

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.

Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research.

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.

Reversible heart rhythm complexity impairment in patients with primary aldosteronism.

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction.

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.

Aldosterone induced galectin-3 secretion in vitro and in vivo: from cells to humans.

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.

Myocardial ultrasound tissue characterization of patients with primary aldosteronism.

Primary aldosteronism (PA), an underdiagnosed cause of hypertension, is associated with more significant cardiac remodeling and myocardial fibrosis than is essential hypertension (EH). The aim of this study was to validate myocardial fibrosis and to evaluate factors associated with the degree of myocardial fibrosis in patients with PA. We prospectively analyzed 62 patients with PA (including 46 patients with aldosterone-producing adenoma and 16 with bilateral hyperplasia) between October 2006 and October 2010, and we enrolled 17 patients with EH as the control group. Echocardiography, including ultrasonic tissue characterization using cyclic variation of integrated backscatter (CVIBS), was performed in individuals in both groups. Among patients with PA, the diastolic blood pressures and plasma aldosterone concentrations were significantly higher than those of patients with EH. Moreover, the serum potassium levels and the plasma renin activities were significantly lower in patients with EH. As observed by echocardiography, patients with PA had greater interventricular septal thickness, greater left ventricular posterior wall thickness, and higher left ventricular mass indexes than did patients with EH. Patients with PA had significantly lower CVIBS values than patients with EH (7.1 ± 2.2 vs. 8.7 ± 1.5 dB; p = .005). In a correlation study that corrected for various clinical parameters, only log-transformed plasma renin activity values correlated significantly with CVIBS values. Ultrasonic tissue characterization with CVIBS is a useful tool for determining the extent of myocardial fibrosis. Patients with PA exhibit a more severe degree of myocardial fibrosis, as detected by CVIBS, than do patients with EH. Moreover, the severity of fibrosis, as detected by CVIBS, correlates with log-transformed plasma renin activity values.

Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism.

OBJECTIVE: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. METHOD: We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. RESULTS: APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone-renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 µg/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 µg/l, P = 0.026). CONCLUSION: Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.

Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma.

CONTEXT: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and is associated with more prominent vascular stiffness and atherosclerosis. However, the effect of adrenalectomy on reversibility of vascular damage is unclear. OBJECTIVE: Our objective was to investigate the vascular changes and possibility of reversibility after adrenalectomy in PA patients. METHODS: We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that received adrenalectomy from October 2006 to December 2008 and 21 patients with essential hypertension (EH) were enrolled as the control group. Carotid intima media thickness (CIMT) measurement by B-mode ultrasound of the right common carotid arteries and pulse wave velocity (PWV) measurement including brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV) were performed in both groups. The follow-up measurements were performed one-year after adrenalectomy in APA group. RESULTS: APA patients had significantly higher diastolic blood pressure, plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR), but lower serum potassium level and plasma renin activity (PRA) than EH patients. APA patients had significantly higher CIMT (0.64±0.13 vs. 0.53±0.10 mm, p=0.006), higher baPWV (1589±296 vs. 1405±187 cm/s, p=0.024) and haPWV (1095±150 vs. 987±114 cm/s, p=0.013) comparing with EH patients. One-year after adrenalectomy, CIMT reduced significantly from 0.64±0.13 mm to 0.59±0.14 mm (p=0.014), and baPWV and haPWV also showed significant reduction (baPWV, 1589±296 to 1463±188 cm/s, p=0.035; haPWV, 1095±150 to 1017±109 cm/s, p=0.019). CONCLUSION: APA patients have higher degree of early atherosclerosis and vascular stiffness. Adrenalectomy not only corrects the high blood pressure and biochemical parameters but also reverse adverse vascular change in APA patients.

Long-term prognosis in ethnic Chinese patients with unprotected left main coronary artery disease.

OBJECTIVE: The aim of this study was to investigate the long-term outcome of unprotected left main coronary artery disease (LMCA) with different therapeutic modalities in Chinese patients. BACKGROUND: Coronary artery bypass graft (CABG) has been considered standard therapy for patients with LMCA disease. Percutaneous coronary intervention (PCI) has recently been alternative choice for unprotected LMCA. Nevertheless, the effects on the long-term outcome of unprotected LMCA by the above-mentioned management in Chinese remains unknown. METHODS: Patients with unprotected LMCA were enrolled at National Taiwan University Hospital from January 1996 to June 2006. Survival outcomes were obtained by the Bureau of National Health Insurance and clinical results were obtained by chart record review and telephone interview. RESULTS: A total of 620 patients with a mean age of 67 +/- 10 years were enrolled and followed up for 1,587 +/- 1,136 days. Of these, 136 were treated with medical therapy, 336 with CABG and 148 with PCI. Clinical outcome of patients receiving medical therapy was the worst. There was no significant difference between the PCI and CABG group in the risk of cardiovascular death. Cox regression analysis showed that cardiovascular mortality was significantly associated with age (P < 0.001), diabetes mellitus (P = 0.004), LVEF (P = 0.001). In high-risk left ventricular dysfunction, the elderly and renal insufficiency patients, the long-term survival was statistically significantly better in the CABG group. CONCLUSION: For Chinese patients with unprotected left main coronary artery disease, a significant higher risk of cardiovascular death was noted in the medical therapy group. Overall the long-term cardiovascular survival was similar in LMCA patients treated with either PCI or CABG, but CABG provided better survival outcome in high-risk subgroup patients.

Intravenous leiomyomatosis with intracardiac extension.

Whereas uterine leiomyoma is a common woman disease, intravenous leiomyomatosis with intracaval and intracardiac complications is a rare condition. The initial presentation is dependent upon the severity of the intracardiac involvement, although complete surgery is the best treatment. The case of a 39-year-old woman is described here, with an initial presentation of dyspnea and right heart failure. Leiomyomatosis originating from the uterus and extending to the inferior vena cava and right atrium was diagnosed from various preoperative studies. The patient was resuscitated because of respiratory failure and severe right heart failure. However, she was operated successfully through a two-stage approach and remained well postoperatively. This case illustrates an intriguing presentation of intravenous leiomyomatosis and a curative surgical intervention even in critical condition.