Targeting interleukin-1β protects from aortic aneurysms induced by disrupted transforming growth factor β signaling

Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations

Celiac vagus nerve stimulation recapitulates angiotensin II-induced splenic noradrenergic activation, driving egress of CD8 effector cells

Angiotensin II (AngII) is a peptide hormone that affects the cardiovascular system, not only through typical effects on the vasculature, kidneys, and heart, but also through less understood roles mediated by the brain and the immune system. Here, we address the hard-wired neural connections within the autonomic nervous system that modulate splenic immunity. Chronic AngII infusion triggers burst firing of the vagus nerve celiac efferent, an effect correlated with noradrenergic activation in the spleen and T cell egress. Bioelectronic stimulation of the celiac vagus nerve, in the absence of other challenges and independently from afferent signals to the brain, evokes the noradrenergic splenic pathway to promote release of a growth factor mediating neuroimmune crosstalk, placental growth factor (PlGF), and egress of CD8 effector T cells. Our findings also indicate that the neuroimmune interface mediated by PlGF and necessary for transducing the neural signal into an effective immune response is dependent on α-adrenergic receptor signaling

TIMP3 interplays with apelin to regulate cardiovascular metabolism in hypercholesterolemic mice

Tissue inhibitor of metalloproteinase 3 (TIMP3) is an extracellular matrix (ECM) bound protein, which has been shown to be downregulated in human subjects and experimental models with cardiometabolic disorders, including type 2 diabetes mellitus, hypertension and atherosclerosis. The aim of this study was to investigate the effects of TIMP3 on cardiac energy homeostasis during increased metabolic stress conditions

Postpartum ovarian vein thrombosis after cesarean delivery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Postpartum ovarian vein thrombosis is an uncommon complication; incidence varies between 0.002% and 0.05%. It most often occurs during the 2–15 days following delivery.</p> <p>Case presentation</p> <p>A 22-year-old pregnant woman at term presented to hospital with uterine contractions, abdominal pain, nausea and vomiting. After delivery an ovarian vein thrombosis was diagnosed.</p> <p>Conclusion</p> <p>Low-molecular weight heparin with broad-spectrum antibiotics are the accepted therapy in non-complicated cases of postpartum ovarian vein thrombosis.</p

The GAPS Programme at TNG : LIV. A He I survey of close-in giant planets hosted by M-K dwarf stars with GIANO-B

Context. Atmospheric escape plays a fundamental role in shaping the properties of exoplanets. The metastable near-infrared (nIR) helium triplet at 1083.3 nm (He I) is a powerful proxy of extended and evaporating atmospheres. Aims: We used the GIARPS (GIANO-B + HARPS-N) observing mode of the Telescopio Nazionale Galileo to search for He I absorption in the upper atmospheres of five close-in giant planets hosted by the K and M dwarf stars of our sample, namely WASP-69 b, WASP-107 b, HAT-P-11 b, GJ 436 b, and GJ 3470 b. Methods: We focused our analysis on the nIR He I triplet, performing high-resolution transmission spectroscopy by comparing the in-transit and out-of-transit observations. In instances where nightly variability in the He I absorption signal was identified, we investigated the potential influence of stellar magnetic activity on the planetary absorption signal by searching for variations in the Hα transmission spectrum. Results: We spectrally resolve the He I triplet and confirm the published detections for WASP-69 b (3.91 ± 0.22%, 17.6σ), WASP-107 b (8.17−0.76+0.80%, 10.5σ), HAT-P-11 b (1.36 ± 0.17%, 8.0σ), and GJ 3470 b (1.75−0.36+0.39%, 4.7σ). We do not find evidence of extra absorption for GJ 436 b. We observe night-to-night variations in the He I absorption signal for WASP-69 b, associated with variability in Hα, which likely indicates the influence of pseudo-signals related to stellar activity. Additionally, we find that the He I signal of GJ 3470 b originates from a single transit observation, thereby corroborating the discrepancies found in the existing literature. An inspection of the Hα line reveals an absorption signal during the same transit event. Conclusions: By combining our findings with previous analyses of GIANO-B He I measurements of planets orbiting K dwarfs, we explore potential trends with planetary and stellar parameters that are thought to affect the absorption of metastable He I. Our analysis is unable to identify clear patterns, thus emphasising the necessity for additional measurements and the exploration of potential additional parameters that may be important in controlling He I absorption in planetary upper atmospheres

Primary aldosteronism: A Japanese perspective

Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 10% of all hypertension. Far from being benign, hypertension due to PA is associated with high cardiovascular morbidity and mortality. However, PA is still underdiagnosed in general practice. Recent reports strongly recommend that identifying patients with PA is cost-beneficial based on improved cardiovascular outcomes afforded by specific surgical and medical treatment. This review provides an update of PA including controversial aspects of diagnosis and treatment

Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism

Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], P<0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], P<0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; P<0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; P=0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS