Self-avoidance allows sister dendrites from the same neuron to form non-redundant coverage of the sensory territory and is important for neural circuitry functions. Here, we report an unexpected, ...cell-autonomous role of the Wnt-secretory factor MIG-14/Wntless in mediating dendrite self-avoidance in the C. elegans multidendritic PVD neurons. Similar findings in Drosophila suggest that this novel function of Wntless is conserved. The mig-14 mutant shows defects in dendrite self-avoidance, and ectopic MIG-14 expression triggers dendrite repulsion. Functions of dendrite self-avoidance and Wnt secretion could be mapped to distinct MIG-14 domains, indicating that these two functions of MIG-14 are genetically separable, consistent with lack of self-avoidance defects in the Wnt mutants. We further demonstrate that MIG-14 engages Wiskott-Aldrich syndrome protein (WASP)-dependent actin assembly to regulate dendrite self-avoidance. Our work expands the repertoire of self-avoidance molecules and uncovers a previously unknown, Wnt-independent function of MIG-14/Wntless.
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•Wntless controls dendrite self-avoidance in C. elegans and Drosophila•Self-avoidance and Wnt signaling are mediated by distinct Wntless protein domains•Wntless displays interaction in trans and is sufficient for dendrite repulsion•Wntless promotes self-avoidance through F-actin cytoskeleton
Dendrites from the same neuron display self-avoidance. Liao et al. identify Wntless, a protein that controls Wnt secretion, as a novel self-avoidance molecule. They show that Wntless acts through F-actin rather than Wnt signaling to promote dendrite repulsion.
Primary aldosteronism (PA) is a common cause of secondary hypertension and is associated with worse cardiovascular outcomes. The elevated aldosterone in PA leads to left ventricular (LV) remodeling ...and dysfunction. In recent decades, clinical studies have demonstrated worse LV remodeling including increased LV mass and cardiac fibrosis in patients with PA compared to patients with essential hypertension. Several mechanisms may explain the process of aldosterone-induced LV remodeling, including directly profibrotic and hypertrophic effects of aldosterone on myocardium, increased reactive oxygen species and profibrotic molecules, dysregulation of extracellular matrix metabolism, endothelium dysfunction and circulatory macrophages activation. LV remodeling causes LV diastolic and systolic dysfunction, which may consequently lead to clinical complications such as heart failure, atrial fibrillation, ischemic heart disease, and other vascular events. Adequate treatment with adrenalectomy or medical therapy can improve LV remodeling and dysfunction in PA patients. In this review, we discuss the mechanisms of aldosterone-induced LV remodeling and provide an up-to-date review of clinical research about LV remodeling-related heart structural changes, cardiac dysfunction, and their clinical impacts on patients with PA.
Endothelial Dysfunction in Primary Aldosteronism Chen, Zheng-Wei; Tsai, Cheng-Hsuan; Pan, Chien-Ting ...
International journal of molecular sciences,
10/2019, Letnik:
20, Številka:
20
Journal Article
Recenzirano
Odprti dostop
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.
Abstract
Context
Primary aldosteronism (PA) patients have a higher degree of arterial stiffness, which can be reversed after adrenalectomy.
Objective
We aimed to compare the reversal of arterial ...stiffness between surgically and medically treated PA patients and to identify the predictors of effective medical treatment.
Methods
We prospectively enrolled 445 PA patients and collected data on baseline clinical characteristics, biochemistry, blood pressure, and pulse wave velocity (PWV) before treatment and 12 months after treatment. In the mineralocorticoid receptor antagonist (MRA)-treated patients, the relationship between the change in PWV after 1 year (ΔPWV) and posttreatment renin activity was explored using the restricted cubic spline (RCS) method.
Results
Of the 445 enrolled PA patients, 255 received adrenalectomy (group 1) and 190 received MRAs. In the RCS model, posttreatment plasma renin activity (PRA) 1.5 ng/mL/h was the best cutoff value. Therefore, we divided the MRA-treated patients into 2 groups: those with suppressed PRA (< 1.5 ng/mL/h, group 2), and those with unsuppressed PRA (≥ 1.5 ng/mL/h, group 3). Only group 1 and group 3 patients had a statistically significant improvement in PWV after treatment (both P < .001), whereas no significant improvement was noted in group 2 after treatment (P = .151). In analysis of variance and post hoc analysis, group 2 had a significantly lower ΔPWV than group 1 (P = .007) and group 3 (P = .031). Multivariable regression analysis of the MRA-treated PA patients identified log-transformed posttreatment PRA, age, and baseline PWV as independent factors correlated with ΔPWV.
Conclusion
The reversal of arterial stiffness was found in PA patients receiving adrenalectomy and in medically treated PA patients with unsuppressed PRA.
Percutaneous angioplasty with the stent was deployed from the left distal superficial femoral artery (SFA) to left external iliac artery (EIA) at first.Relevant Test Results Prior to Catheterization ...Vascular echo study showed the poor waveform and poor flow over the right common femoral artery (CFA) and left SFA. Total occlusion was found at the whole right common femoral artery (CFA) with distal collateral branches to superficial femoral artery (SFA) and deep femoral artery (DFA).Interventional Management Procedural Step We accessed bidirectionally via right brachial artery with 6 Fr sheath and right SFA with 4 Fr sheath, but we failed to cross antegrade Fielder FC with CXI 2.6 FR 150 cm through right CIA using JR 4. Final angiography showed revascularized right CFA and improved the flow of EIA and CIA without any complication.Conclusions Successful retrograde wiring via right EIA access for right CIA stenosis with subsequent successful bidirectional wiring and revascularization to right CFA total occlusion.
Sludge adsorbent (SA) and commercial activated carbon fibers (ACFC and ACFT) were applied to Orange II and Chrysophenine (CH) adsorption (BET surface area: ACFC
>
ACFT
>
SA). ACFT was primarily in ...the micropore range, while SA was ∼500
Å (macropore) and 80
Å (mesopore). The ACFC pore volume was high in both the mesopore and micropore regions. Measurement of the oxygen surface functional groups of the adsorbents using Boehm's titration method showed a similar distribution on the carbon fibers (mainly in the carbonyl group), while SA was mainly in the carboxyl, lactone and phenolic groups. The SA, ACFC and ACFT adsorption capacities of Orange II (30–80
mg/l) ranged from 83 to 270, 209–438, and 25–185
mg/g at temperatures ranging from 10 to 60
°C, respectively. CH concentration ranged from 30 to 80
mg/l, corresponding to SA and ACFC adsorption capacities of 39–191 and 48–374
mg/g over the defined temperature range, from 10 to 60
°C. CH adsorption on ACFT was low. The adsorption capacity of Orange II on ACFT was lower than on SA at 10
oC, but at higher temperatures the Orange II molecules were transported into the ACFT, producing an adsorption capacity similar to that of SA. Mass transfer increased with temperature, overcoming the adsorption energy barrier. Overall, SA and ACFC were more effective than ACFT.
Primary aldosteronism (PA) is the most common form of endocrine hypertension, characterized by excess aldosterone production that leads to an increased risk of cardiovascular events and target organ ...damage. Both adrenalectomy and medical treatment have shown efficacy in improving clinical outcomes and comorbidities associated with PA, including a specific subtype of PA with autonomous cortisol secretion (ACS). Understanding the comorbidities of PA and establishing appropriate follow-up protocols after treatment are crucial for physicians to enhance morbidity and mortality outcomes in patients with PA. Additionally, the screening for hypercortisolism prior to surgery is essential, as the prognosis of patients with coexisting PA and ACS differs from those with PA alone. In this review, we comprehensively summarize the comorbidities of PA, encompassing cardiovascular, renal, and metabolic complications. We also discuss various post-treatment outcomes and provide insights into the strategy for glucocorticoid replacement in patients with overt or subclinical hypercortisolism. This clinical practice guideline aims to equip medical professionals with up-to-date information on managing concurrent hypercortisolism, assessing treatment outcomes, and addressing comorbidities in patients with PA, thereby improving follow-up care.
Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was ...developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.
Spontaneous intracerebral hemorrhage (sICH) has a high mortality rate. Research has demonstrated that the occurrence of sICH is related to air pollution. This study used big data analysis to explore ...the impact of air pollution on the risk of sICH in patients of differing age and geographic location. 39,053 cases were included in this study; 14,041 in the Taipei region (Taipei City and New Taipei City), 5537 in Taoyuan City, 7654 in Taichung City, 4739 in Tainan City, and 7082 in Kaohsiung City. The results of correlation analysis indicated that there were two pollutants groups, the CO and NO₂ group and the PM
and PM
group. Furthermore, variations in the correlations of sICH with air pollutants were identified in different age groups. The co-factors of the influence of air pollutants in the different age groups were explored using regression analysis. This study integrated Taiwan National Health Insurance data and air pollution data to explore the risk factors of sICH using big data analytics. We found that PM
and PM
are very important risk factors for sICH, and age is an important modulating factor that allows air pollutants to influence the incidence of sICH.
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