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https://www.readbyqxmd.com/read/29655829/renal-effects-and-associated-outcomes-during-angiotensin-neprilysin-inhibition-in-heart-failure
#1
Kevin Damman, Mauro Gori, Brian Claggett, Pardeep S Jhund, Michele Senni, Martin P Lefkowitz, Margaret F Prescott, Victor C Shi, Jean L Rouleau, Karl Swedberg, Michael R Zile, Milton Packer, Akshay S Desai, Scott D Solomon, John J V McMurray
OBJECTIVES: The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction. BACKGROUND: Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system. METHODS: In the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart failure with reduced ejection fraction were randomized to treatment with sacubitril/valsartan or enalapril...
April 5, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29652095/decrease-in-neprilysin-and-vasoconstrictors-and-increase-in-vasodilators-following-bariatric-surgery
#2
Husam Ghanim, Scott Monte, Joseph Caruana, Kelly Green, Sanaa Abuaysheh, Paresh Dandona
Since morbid obesity is associated with congestive cardiac failure and hypertension, and gastric bypass surgery is followed by a reduction in blood pressure and in the risk of congestive cardiac failure, we hypothesized that weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of renin angiotensin system (RAS), catecholamines and endothelin-1 with an increase in the concentrations of vasodilators...
April 13, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29643067/incidence-predictors-and-outcomes-associated-with-hypotensive-episodes-among-heart-failure-patients-receiving-sacubitril-valsartan-or-enalapril-the-paradigm-hf-trial-prospective-comparison-of-angiotensin-receptor-neprilysin-inhibitor-with-angiotensin-converting
#3
Orly Vardeny, Brian Claggett, Jessica Kachadourian, Scott M Pearson, Akshay S Desai, Milton Packer, Jean Rouleau, Michael R Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J V McMurray, Scott D Solomon
BACKGROUND: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients...
April 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29626018/drug-therapies-in-chronic-heart-failure-a-focus-on-reduced-ejection-fraction
#4
Helena Bolam, Geraint Morton, Paul R Kalra
There are multiple evidence-based drug treatments for chronic heart failure (HF), both disease-modifying agents and those for symptom control. The majority of the evidence base supports drugs used in HF with reduced left ventricular ejection fraction. The mainstay of disease modification involves manipulation of neurohormonal activation that occurs in HF. In addition to established angiotensin-converting enzyme inhibitors, beta blockers and mineralocorticoid receptor antagonists (MRAs), newer agents are now available such as the angiotensin receptor neprilysin inhibitors...
March 2018: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/29614686/the-effect-of-chronic-cerebral-hypoperfusion-on-amyloid-%C3%AE-metabolism-in-a-transgenic-mouse-model-of-alzheimer-s-disease-ps1v97l
#5
Heyun Yang, Tingting Hou, Wei Wang, Yumin Luo, Feng Yan, Jianping Jia
Alzheimer's disease (AD) and cerebrovascular disease often coexist. However, it is difficult to determine how chronic cerebral hypoperfusion affects the metabolism of amyloid-β peptides (Aβ) in a living patient with AD. Thus, we developed an animal model of this condition, using transgenic mice (PS1V97L) and right common carotid artery ligation to create chronic cerebral hypoperfusion. The metabolic processes associated with amyloid-β peptide (Aβ) were observed and evaluated in this PS1V97L plus hypoperfusion model...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29607920/nobiletin-reduces-intracellular-and-extracellular-%C3%AE-amyloid-in-ips-cell-derived-alzheimer-s-disease-model-neurons
#6
Junko Kimura, Kosuke Shimizu, Koji Kajima, Akihito Yokosuka, Yoshihiro Mimaki, Naoto Oku, Yasushi Ohizumi
Alzheimer's disease (AD) is the most common cause of dementia, with progressive memory impairment. Recently, neprilysin, a β-amyloid (Aβ)-degrading enzyme has become featured as a drug target for AD. Previously, we identified nobiletin from citrus peels as a natural compound possessing anti-dementia activity. In addition, we demonstrated that nobiletin improved memory in memory-impaired animals and, further, that Aβ levels were markedly decreased in the brains of these animals. We demonstrated in vitro that nobiletin up-regulates neprilysin expression and activity in human neuroblastoma cells...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29603541/augmentation-of-glucagon-like-peptide-1-receptor-signalling-by-neprilysin-inhibition-potential-implications-for-patients-with-heart-failure
#7
REVIEW
Milton Packer
Augmentation of glucagon-like peptide-1 (GLP-1) receptor signalling is an established approach to the treatment of type 2 diabetes. However, endogenous GLP-1 and long-acting GLP-1 receptor analogues are degraded not only by dipeptidyl peptidase-4, but also by neprilysin. This observation raises the possibilities that endogenous GLP-1 contributes to the clinical effects of neprilysin inhibition and that patients concurrently treated with sacubitril/valsartan and incretin-based drugs may experience important drug-drug interactions...
March 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29596012/utility-of-natriuretic-peptides-to-assess-and-manage-patients-with-heart-failure-receiving-angiotensin-receptor-blocker-neprilysin-inhibitor-therapy
#8
Alan S Maisel, Lori B Daniels, Inder S Anand, Peter A McCullough, Sheryl L Chow
Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP...
March 29, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29595329/sacubitril-and-valsartan-protect-from-experimental-myocardial-infarction-by-ameliorating-oxidative-damage-in-wistar-rats
#9
Mohd Imran, Md Quamrul Hassan, Md Sayeed Akhtar, Obaid Rahman, M Akhtar, Abul Kalam Najmi
BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL)...
March 29, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29563991/tongluo-xingnao-effervescent-tablet-reverses-memory-deficit-and-reduces-plaque-load-in-appswe-ps1de9-mice
#10
Wenjun Fu, Yuan Dai, Tao Ma, Jiangping Wei, Huan Chen, Shijun Xu
Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β (Aβ)-induced neurodegeneration is hypothesized to be the primary pathological mechanism of AD. Tongluo Xingnao effervescent tablets (TXET), based on the traditional Chinese formula Qionggui Tang, have been used to treat AD and other types of dementia in China for decades. In the present study, the effects of TXET on cognition deficit, amyloid-β production, amyloid precursor protein procession and β-secretase expression were investigated in the APPswe/PS1dE9 mouse model of AD...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29561187/increased-urinary-angiotensin-converting-enzyme-2-ace2-and-neprilysin-nep-in-type-2-diabetic-patients
#11
Sridevi Gutta, Nadja Grobe, Meenasri Kumbaji, Hassan Osman, Mohammad Saklayen, Gengxin Li, Khalid M Elased
ACE2 and NEP are metalloproteases which are highly expressed in the renal proximal tubules. ACE2 and NEP generate renoprotective angiotensin (1-7) from angiotensin II (Ang II) and Ang I, respectively, and therefore could have a major role in chronic kidney disease (CKD). Recent data demonstrated increased urinary ACE2 in diabetic patients with CKD and kidney transplants. We tested the hypothesis that urinary ACE2, NEP and ADAM17 are increased and could be risk predictors of CKD in diabetic patients. Urinary and plasma ACE2, NEP, and ADAM17 were investigated in twenty healthy nondiabetics (ND), and forty diabetic patients with normoalbuminuria (Dnormo), microalbuminuria (Dmicro) and macroalbuminuria (Dmacro) using ELISA, Western blot, fluorogenic and novel mass spectrometric-based enzyme assays...
March 21, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29553871/neprilysin-deficiency-is-associated-with-expansion-of-islet-%C3%AE-cell-mass-in-high-fat-fed-mice
#12
Jacqueline H Parilla, Rebecca L Hull, Sakeneh Zraika
Neprilysin (NEP) is an endopeptidase known to modulate nervous, cardiovascular, and immune systems via inactivation of regulatory peptides. In addition, it may also contribute to impaired glucose homeostasis as observed in type 2 diabetes (T2D). Specifically, we and others have shown that NEP is upregulated under conditions associated with T2D, whereas NEP deficiency and/or inhibition improves glucose homeostasis via enhanced glucose tolerance, insulin sensitivity, and pancreatic β-cell function. Whether increased β-cell mass also occurs with lack of NEP activity is unknown...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29546540/cardiac-unloading-by-lvad-support-differentially-influences-components-of-the-cgmp-pkg-signaling-pathway-in-ischemic-and-dilated-cardiomyopathy
#13
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
https://www.readbyqxmd.com/read/29544929/angiotensin-receptor-neprilysin-inhibition-provides-superior-cardioprotection-compared-to-angiotensin-converting-enzyme-inhibition-after-experimental-myocardial-infarction
#14
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
https://www.readbyqxmd.com/read/29542073/combination-therapy-of-renin-angiotensin-system-inhibitors-and-%C3%AE-blockers-in-patients-with-heart-failure
#15
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
https://www.readbyqxmd.com/read/29532764/entresto-a-new-panacea-for-heart-failure
#16
Peter H Khalil, Ghazal Kabbach, Debabrata Mukherjee, Sarmad Said
Heart Failure (HF) is one of the main health care burdens in the United States and in the world. Many drugs are approved and used in practice for management of this condition; including beta blockers, diuretics, aldosterone antagonists, angiotensin converting enzyme inhibitors (ACEI's), and angiotensin receptor blockers (ARBs). Recently, the Food and Drug Administration (FDA) approved a drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection Fraction (HFrEF) patients instead of ACEI's and ARBs...
March 13, 2018: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29529959/impact-of-prolonged-utilization-of-neprilysin-inhibition-on-the-cognitive-function-of-heart-failure-patients
#17
Niel N Shah, Muhammad U Dogar, Parin N Shah, Sameera Ishtiaq, Shawn Mathew, Pratik Shah, Alia Ishtiaq, Timothy J Vittorio
No abstract text is available yet for this article.
March 1, 2018: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/29525327/obesity-related-heart-failure-with-a-preserved-ejection-fraction-the-mechanistic-rationale-for-combining-inhibitors-of-aldosterone-neprilysin-and-sodium-glucose-cotransporter-2
#18
REVIEW
Milton Packer, Dalane W Kitzman
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired...
March 7, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29502102/combined-angiotensin-receptor-neprilysin-inhibitors-improve-cardiac-and-vascular-function-via-increased-no-bioavailability-in-heart-failure
#19
Rishi K Trivedi, David J Polhemus, Zhen Li, Daniel Yoo, Hiroshi Koiwaya, Amy Scarborough, Traci T Goodchild, David J Lefer
BACKGROUND: There is a paucity of data about the mechanisms by which sacubitril/valsartan (also known as LCZ696) improves outcomes in patients with heart failure. Specifically, the effects of sacubitril/valsartan on vascular function and NO bioavailability have not been investigated. We hypothesized that sacubitril/valsartan therapy increases circulating NO levels and improves vascular function in the setting of heart failure. METHODS AND RESULTS: Male spontaneously hypertensive rats underwent myocardial ischemia/reperfusion surgery to induce heart failure and were followed for up to 12 weeks with serial echocardiography...
March 3, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29500454/the-effects-of-angiotensin-receptor-neprilysin-inhibition-by-sacubitril-valsartan-on-adipose-tissue-transcriptome-and-protein-expression-in-obese-hypertensive-patients
#20
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
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