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Natriuretic peptide receptor

Raffaele Altara, Fouad A Zouein, Rita Dias Brandão, Saeed N Bajestani, Alessandro Cataliotti, George W Booz
Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences...
2018: Frontiers in Cardiovascular Medicine
Marcello Panagia, Howard H Chen, Dominique Croteau, Yin-Ching Iris Chen, Chongzhao Ran, Ivan Luptak, Lee Josephson, Wilson S Colucci, David E Sosnovik
BACKGROUND: Substrate utilization in tissues with high energetic requirements could play an important role in cardiometabolic disease. Current techniques to assess energetics are limited by high cost, low throughput, and the inability to resolve multiple readouts simultaneously. Consequently, we aimed to develop a multiplexed optical imaging platform to simultaneously assess energetics in multiple organs in a high throughput fashion. METHODS AND RESULTS: The detection of 18F-Fluordeoxyglucose uptake via Cerenkov luminescence and free fatty acid uptake with a fluorescent C16 free fatty acid was tested...
March 2018: Circulation. Cardiovascular Imaging
Sven Persoon, Michael Paulus, Stephan Hirt, Carsten Jungbauer, Alexander Dietl, Andreas Luchner, Christof Schmid, Lars S Maier, Christoph Birner
Implantation of left ventricular assist devices (LVADs) as bridge to transplant in end-stage heart failure allows for analyzing reverse remodeling processes of the supported heart. Whether this therapy influences the cGMP-PKG signaling pathway, which is currently under thorough investigation for developing new heart failure therapeutics, is unknown. In fourteen end-stage heart failure patients (8 with dilated cardiomyopathy, DCM; 6 with ischemic cardiomyopathy, ICM) tissue specimens of left ventricles were collected at LVAD implantation and afterwards at receiver heart explantation, respectively...
March 15, 2018: Heart and Vessels
Andrew R Kompa, Jiayu Lu, Thomas J Weller, Darren J Kelly, Henry Krum, Thomas G von Lueder, Bing H Wang
BACKGROUND: Angiotensin receptor neprilysin inhibitor (ARNi) enhances beneficial natriuretic peptides by inhibiting their breakdown through neprilysin. Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce. ARNi may be superior to ACEi in attenuating adverse cardiac remodeling and dysfunction post-myocardial infarction (MI)...
May 1, 2018: International Journal of Cardiology
Kotaro Nochioka, Yasuhiko Sakata, Hiroaki Shimokawa
Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system play crucial roles in heart failure with reduced ejection fraction (HFrEF). Clinical trials provide strong evidence of prognostic benefits for combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and β-blocker in the treatment of HFrEF. Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and an alternative for patients who are intolerant to ACEI. Prognostic evidence for triple therapy which combined angiotensin receptor blocker (ARB) and ACEI in addition to β-blocker therapy, is still controversial in HFrEF...
March 15, 2018: Advances in Experimental Medicine and Biology
M P De Cesaro, J T Dos Santos, J G Ferst, J E Nóbrega, Pra Rosa, M T Rovani, G F Ilha, R C Bohrer, R Ferreira, B G Gasperin, V Bordignon, Pbd Gonçalves
Natriuretic peptides (NPs) are known to regulate reproductive events in polyovulatory species, but their function and regulation in monovulatory species remain to be fully characterized. Using a well-established in vivo model, we found that bovine granulosa cells from follicles near the deviation stage express mRNA for the three NP receptors (NPR1, NPR2 and NPR3), but not for NP precursors (NPPA, NPPB and NPPC). The abundance of NPR3 mRNA was higher in dominant compared to subordinate follicles at the expected time of follicular deviation...
March 14, 2018: Reproduction in Domestic Animals, Zuchthygiene
Xiao Wang, Huarong Wang, Wei Liu, Zhiyuan Zhang, Yanhao Zhang, Wenqiang Zhang, Zijiang Chen, Guoliang Xia, Chao Wang
Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9%-18% of reproductive-age women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation...
March 13, 2018: Clinical Science (1979-)
Milton Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
March 12, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Yang Gu, Donna Thompson, Jie Xu, David F Lewis, John A Morgan, Danielle B Cooper, Charles E McCathran, Yuping Wang
OBJECTIVE: Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signaling is present in maternal vascular system in preeclampsia. STUDY DESIGN: Maternal venous blood was obtained from 197 pregnant women (84 normotensive, 16 complicated with chronic hypertension (CHT), 11 mild and 86 severe preeclampsia)...
January 2018: Pregnancy Hypertension
Qingyi Ma, Lubo Zhang
Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups...
March 5, 2018: Experimental Neurology
R Stinkens, B W van der Kolk, J Jordan, T Jax, S Engeli, T Heise, J W Jocken, M May, C Schindler, B Havekes, N Schaper, D Albrecht, S Kaiser, N Hartmann, M Letzkus, T H Langenickel, G H Goossens, E E Blaak
Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients...
March 2, 2018: Scientific Reports
Kanza Benomar, Stéphanie Espiard, Camille Loyer, Arnaud Jannin, Marie-Christine Vantyghem
Natriuretic peptides are a group of hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C type (CNP), urodilatin and guanilyn. ANP (half-life: 2-4 min), is secreted by the atrium, BNP (half-life: 20 min) by the ventricle, CNP by the vascular endothelium, urodilatin by the kidney and guanylin by the intestine. These natriuretic peptides prevent water and salt retention through renal action, vasodilatation and hormonal inhibition of aldosterone, vasopressin and cortisol. These peptides also have a recently demonstrated metabolic effect through an increase of lipolysis, thermogenesis, beta cell proliferation and muscular sensitivity to insulin...
February 26, 2018: La Presse Médicale
Milton Packer
Among patients with heart failure and a preserved ejection (HFpEF), obesity is associated with a distinct phenotype that is characterized by adiposity-driven plasma volume expansion and cardiac overfilling, which is coupled with an impairment of ventricular distensibility. These pathophysiological abnormalities may be related to the increased actions of specific adipocyte-derived signalling molecules (aldosterone, neprilysin and leptin) that work in concert with increased renal sympathetic nerve traffic and activated beta2 -adrenergic receptors to promote sodium retention, microvascular rarefaction, cardiac fibrosis and systemic inflammation...
March 1, 2018: European Journal of Heart Failure
Philip Tröster, Julia Haseleu, Jonas Petersen, Oliver Drees, Achim Schmidtko, Frederick Schwaller, Gary R Lewin, Gohar Ter-Avetisyan, York Winter, Stefanie Peters, Susanne Feil, Robert Feil, Fritz G Rathjen, Hannes Schmidt
A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI ( Npr2 fl / fl ;Wnt1 Cre and cGKI KO / fl ;Wnt1 Cre ) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice...
2018: Frontiers in Molecular Neuroscience
Rebecca Sullivan, Rebecca McGirr, Shirley Hu, Alice Tan, Derek Wu, Carlie Charron, Tyler Lalonde, Edith Arany, Subrata Chakrabarti, Leonard Luyt, Savita Dhanvantari
Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5 after birth...
February 1, 2018: Journal of the Endocrine Society
Arianna Colini Baldeschi, Eugenia Pittaluga, Federica Andreola, Simona Rossi, Mauro Cozzolino, Giuseppe Nicotera, Gianluca Sferrazza, Pasquale Pierimarchi, Annalucia Serafino
In the last decades increasing evidence indicated a crucial role of the Wnt/β-catenin signaling in development of midbrain dopaminergic (mDA) neurons. Recently dysregulation of this pathway has been proposed as a novel pathomechanism leading to Parkinson's disease (PD) and some of the molecules participating to the signaling have been evaluated as potential therapeutic targets for PD. Atrial natriuretic peptide (ANP) is a cardiac-derived hormone having a critical role in cardiovascular homeostasis. ANP and its receptors (NPRs) are widely expressed in mammalian central nervous system (CNS) where they could be implicated in the regulation of neural development, synaptic transmission and information processing, as well as in neuroprotection...
2018: Frontiers in Aging Neuroscience
Speranza Rubattu, Sebastiano Sciarretta, Simona Marchitti, Franca Bianchi, Maurizio Forte, Massimo Volpe
Atrial natriuretic peptide (ANP) is a cardiac hormone which plays important functions to maintain cardio-renal homeostasis. The peptide structure is highly conserved among species. However, a few gene variants are known to fall within the human ANP gene. The variant rs5065 (T2238C) exerts the most substantial effects. The T to C transition at the 2238 position of the gene (13-23% allele frequency in the general population) leads to the production of a 30-, instead of 28-, amino-acid-long α-carboxy-terminal peptide...
February 11, 2018: International Journal of Molecular Sciences
Tong Zhang, Xiaomei Fan, Ruilan Li, Chunqiang Zhang, Jiaxin Zhang
In vitro produced mammalian embryos suffer from developmental failure, with a large proportion showing embryonic retardation, degradation, or apoptosis. This failure is due, in part, to incomplete oocyte cytoplasmic maturation. C-type natriuretic peptide (CNP) has been reported to act as a meiotic inhibitor. Here we explored the potential effects of CNP pre-treatment sheep oocytes on nuclear maturation, changes in mitochondrial behavior and developmental competence of in vitro fertilized embryos. Sheep cumulus-oocyte complexes (COCs) were aspirated from abattoir-derived ovaries...
February 8, 2018: Biochemical and Biophysical Research Communications
Gianluigi Savarese, Nicola Orsini, Camilla Hage, Ola Vedin, Francesco Cosentino, Giuseppe M C Rosano, Ulf Dahlström, Lars H Lund
OBJECTIVES: The purpose of this study was to assess the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiovascular (CV) versus non-CV events and between NT-proBNP and potential treatment effects in heart failure (HF) with preserved, mid-range, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF, respectively) and clinically relevant subgroups. BACKGROUND: Optimizing patient eligibility criteria in HF trials requires biomarkers that enrich for CV but not for non-CV events and select patients most likely to respond to the tested intervention...
February 1, 2018: JACC. Heart Failure
Jianghui Meng, Masaki Moriyama, Micha Feld, Joerg Buddenkotte, Timo Buhl, Attila Szöllösi, Jingming Zhang, Paul Miller, Andre Ghetti, Michael Fischer, Peter W Reeh, Chunxu Shan, Jiafu Wang, Martin Steinhoff
BACKGROUND: T helper type 2 cell-released interleukin 31 (IL-31) is a critical mediator in atopic dermatitis (AD), a prevalent and debilitating chronic skin disorder. Brain-derived natriuretic peptide (BNP) has been described as a central itch mediator. The importance of BNP in peripheral (skin-derived) itch and its functional link to IL-31 within the neuro-immune axis of the skin is unknown. OBJECTIVE: To investigate the function of BNP in the peripheral sensory system and skin in IL-31-induced itch and neuro-epidermal communication in AD...
February 7, 2018: Journal of Allergy and Clinical Immunology
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