ArticleCirculation. Heart failure2019
Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts.
Article in Circulation. Heart failure, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04128891 (PRospectIve Study of Sacubitril/ValsarTan on MyocardIal OxygenatioN and Fibrosis in PatiEnts With Heart Failure and Preserved Ejection Fraction), which is not on this map. Cited by 96 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PRospectIve Study of Sacubitril/ValsarTan on MyocardIal OxygenatioN and Fibrosis in PatiEnts With Heart Failure and Preserved Ejection Fraction
Who cites it
96 citing papers in PubMed, 143 citations in OpenAlex.
- Effects of sacubitril/valsartan on hypertensive heart disease: the REVERSE-LVH randomized phase 2 trial.Nature communications · 2025Trial
- Angiotensin Receptor-Neprilysin Inhibitor Is Associated With Improved Cardiac Autonomic Function in Heart Failure.Journal of the American Heart Association · 2024Trial
- The Relationship between Angiotensin-Neprilysin Treatment, Echocardiographic Parameters, and NT-proBNP Levels in HFpEF Patients with Acute Decompensated Heart Failure.Computational and mathematical methods in medicine · 2022Trial
- 3-Dimensional Human iPSC-Derived Cardiac Organoids for Antifibrotic Drug Screening.Circulation research · 2026Article
- Dual Empagliflozin and Sacubitril/Valsartan Therapy Improves Ex Vivo Cardiac Function in a Rat Model of Heart Failure.Biomedicines · 2026Article
- Zinc finger BED-type containing 6 (ZBED6) ameliorates cardiac fibrosis by inhibiting Piezo1 transcription and YAP nuclear translocation.Acta pharmacologica Sinica · 2026Article
- Sacubitril/valsartan as a modulator of pulmonary fibrosis: insights into Lnc-SNHG-16/miR-455 modulation and Notch/Smad-3 pathway inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Sacubitril/Valsartan Fails to Ameliorate Cisplatin-Induced Cognitive Impairment.Drug design, development and therapy · 2026Article
- Reversal of left ventricular hypertrophy with sacubitril/valsartan vs. standard antihypertensive agents in hypertension: a systematic review and network meta-analysis.Frontiers in cardiovascular medicine · 2026Review
- Sacubitril/valsartan mitigates cisplatin-induced liver injury through modulation of oxidative stress, Caspase-3 activity, and RXR-α signaling in experimental rats.Frontiers in pharmacology · 2026Article
- Location and aetiology are determinants of fibroblast activation and heterogeneity in the failing human heart.Genome medicine · 2025Article
- Inflammasomes as Potential Therapeutic Targets to Prevent Chronic Active Viral Myocarditis-Translating Basic Science into Clinical Practice.International journal of molecular sciences · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Endomyocardial fibrosis: recent advances and future therapeutic targets.Nature reviews. Cardiology · 2025Review
- RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats in youth treated with a ARNI versus ARB.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Article
- Increased neprilysin expression is linked to atrial fibrotic remodeling in cardiovascular surgery patients.International journal of cardiology. Heart & vasculature · 2025Article
- Sacubitril/valsartan preserves regional cardiac function following myocardial infarction in rats.ESC heart failure · 2025Article
- Relevance of Targeting Oxidative Stress, Inflammatory, and Pro-Resolution Mechanisms in the Prevention and Management of Postoperative Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2025Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Background Heart failure (HF) is invariably accompanied by development of cardiac fibrosis, a form of scarring that increases muscular tissue rigidity and decreases cardiac contractility. Cardiac fibrosis arises from a pathological attempt to repair tissue damaged during maladaptive remodeling. Treatment options to block or reverse fibrosis have proven elusive. Neprilysin is an endopeptidase that degrades vasoactive peptides, including atrial natriuretic peptide. Thus, neprilysin inhibition reduces hypertension, ultimately limiting maladaptive cardiac remodeling. LCZ696, which consists of an angiotensin receptor blocker (valsartan [VAL]) and a neprilysin inhibitor (sacubitril [SAC]), was shown to be well tolerated and significantly reduced the risk of death and hospitalization in HF patients with reduced ejection fraction. We hypothesized that SAC/VAL directly inhibits fibroblast activation and development of pathological fibrosis. Methods and Results We used a mouse model of left ventricle pressure overload coupled to in vitro studies in primary mouse and human cardiac fibroblasts (CFs) to study the impact of SAC/VAL on CF activation and cardiac fibrosis. SAC/VAL significantly ameliorated pressure overload-induced cardiac fibrosis by blocking CF activation and proliferation, leading to functional improvement. Mechanistically, the beneficial impact of SAC/VAL at least partially stemmed from restoration of PKG (protein kinase G) signaling in HF patient-derived CF, which inhibited Rho activation associated with myofibroblast transition. Conclusions This study reveals that SAC/VAL acts directly on CF to prevent maladaptive cardiac fibrosis and dysfunction during pressure overload-induced hypertrophy and suggests that SAC/VAL should be evaluated as a direct antifibrotic therapeutic for conditions such as HF with preserved ejection fraction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.