ArticleJournal of the American Heart Association2016
Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.Journal of translational medicine · 2026Article
- AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis.Journal of advanced research · 2025Article
- Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI.Acta diabetologica · 2024Article
- Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.Acta pharmacologica Sinica · 2024Review
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Distribution of cardiomyocyte-selective adeno-associated virus serotype 9 vectors in swine following intracoronary and intravenous infusion.Physiological genomics · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Large animal models of heart failure with preserved ejection fraction.Heart failure reviews · 2022Review
- Mechanism-Driven Modeling to Aid Non-invasive Monitoring of Cardiac FunctionFrontiers in medical technology · 2022Article
- Tadalafil ameliorates bladder overactivity by restoring insulin-activated detrusor relaxation via the bladder mucosal IRS/PI3K/AKT/eNOS pathway in fructose-fed rats.Scientific reports · 2021Article
- Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success.JACC. Basic to translational science · 2020Review
- Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.JACC. Basic to translational science · 2019Article
- Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure.Scientific reports · 2019Article
- Intramyocardial Injections to De-Stiffen the Heart: A Subject-Specific in Silico Approach.Molecular & cellular biomechanics : MCB · 2019Article
- Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection?Heart (British Cardiac Society) · 2018Review
- Chronic interval exercise training prevents BKJournal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin.Cardiovascular diabetology · 2018Review
- Chronic low-intensity exercise attenuates cardiomyocyte contractile dysfunction and impaired adrenergic responsiveness in aortic-banded mini-swine.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- Loss of Female Sex Hormones Exacerbates Cerebrovascular and Cognitive Dysfunction in Aortic Banded Miniswine Through a Neuropeptide Y-CaJournal of the American Heart Association · 2017Article
- Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension.Journal of translational medicine · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. METHODS AND
resultsWe assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals.
conclusionsBoth saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function.
Indexed as
Identifiers
What OpenQuestion holds
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.