The Endothelial Dysfunction Could Be a Cause of Heart Failure with Preserved Ejection Fraction Development in a Rat Model

Dupas, Thomas; Pelé, Thomas; Dhot, J.; Burban, Mélanie; Persello, Antoine; Aillerie, Virginie; Erraud, Angélique; Tesse, Angela; Stevant, D.; Blangy-Letheule, Angélique; Menguy, Céline; Sauzeau, Vincent; Waard, Michel De; Rozec, Bertrand; Gauthier, Chantal; Lauzier, Benjamin

doi:10.1155/2022/7377877

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Another prevailing theory is that obesity-associated HFpEF is driven by a comorbidity-induced systemic proinflammatory state [ 39 – 41 ]. For example, the microRNA miR-181c is differentially expressed in patients with diabetes and comorbid HFpEF, and overexpression of miR-181c has been associated with proinflammatory conditions [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry

Bae,

Kallenbach,

Nelson

et al. 2024

BMC Endocr Disord

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Background The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. Methods We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0–3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. Results This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. Conclusion Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

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Section: Discussionmentioning

confidence: 99%

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry

Bae,

Kallenbach,

Nelson

et al. 2024

BMC Endocr Disord

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“…Data were obtained by measuring the overall peak amplitude of the generated spectra and normalizing it to the sample's dry weight in arbitrary units (A.U.) [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Vasorelaxant Effect of Moroccan Cannabis sativa Threshing Residues on Rat Mesenteric Arterial Bed is Endothelium and Muscarinic Receptors Dependent

Mahou

Chda

Es‐Safi

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Introduction. Ethanolic fraction of Moroccan Cannabis sativa threshing residues (EFCS) was evaluated for its vasorelaxant activity. The current work aims to identify the active metabolites in the ethanolic fraction of the EFCS and illustrate their mechanism of action. Methods. Free radical scavenging capacity of EFCS was assessed using DPPH method. The EFCS vasodilation activities in phenylephrine-precontracted isolated rat mesenteric arterial beds were investigated in presence of L-NAME (nitric oxide synthase inhibitor), indomethacin (cyclooxygenase inhibitor), potassium channel blockers (namely tetraetylamonium, barium chloride, and glibenclamide), and atropine. Nitric oxide vascular release was measured by electron paramagnetic resonance (EPR) using a spin trap in rat aortic rings. Results. EFCS induced dose-dependent vasorelaxation on mesenteric vascular bed. Incubation of the preparations with L-NAME, ODQ (a soluble guanylyl cyclase inhibitor), or potassium channel blockers reduced the fall of perfusion pressure caused by EFCS. Endothelial denudation or atropine abolished the EFCS’s vasorelaxant effect, suggesting involvement of muscarinic receptors and endothelium-relaxing factors. The extract induced nitric oxide release in aortic rings in a similar manner as acetylcholine suggesting an effect of EFCS on the muscarinic receptor and the conductance arteries. Chemical investigation of EFCS identified potential active components namely apigenin and derivatives of luteolin skeleton and also additional components such as neophytadiene, squalene, and β-sitosterol. In conclusion, the vasorelaxant effect of EFCS on rat mesenteric arterial bed, which is dependent of muscarinic receptor activation, nitric oxide, and EDHF, can account for potential therapeutic use against high blood pressure related cardiovascular diseases.

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“…Second, GHRH-A restored several markers of myocardial inflammation to normal. Endothelial dysfunction has been proposed to link chronic systemic inflammation with myocardial dysfunction and remodeling in HF (41)(42)(43). Schiattarella et al (23) suggested a role of iNOS activation and metabolic inflammation in HFpEF pathogenesis.…”

Section: Effect Of Ghrh-agonist Mr-356 On Inflammationmentioning

confidence: 99%

Efficacy of a Growth Hormone-Releasing Hormone Agonist in a Murine Model of Cardiometabolic Heart Failure with Preserved Ejection Fraction

Kanashiro‐Takeuchi

Takeuchi

Dulce

et al. 2022

Preprint

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Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major unmet medical need owing to its diverse pathophysiology and lack of effective therapies. Potent synthetic, agonists (MR-356 and MR409) of growth hormone-releasing hormone (GHRH) improve the phenotype of models of HF with reduced ejection fraction (HFrEF) and in cardiorenal models of HFpEF. Endogenous GHRH exhibits a broad range of regulatory influences in the cardiovascular (CV) system, aging and plays a role in several cardiometabolic conditions including obesity and diabetes. Whether agonists of GHRH can improve the phenotype of cardiometabolic HFpEF remains untested and unknown. Here we tested the hypothesis that MR-356 can mitigate/reverse the cardiometabolic HFpEF phenotype. C57BL6N mice received a high fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals were randomized to receive daily injections of MR-356 or placebo during a 4-week period. Control animals received no HFD+L-NAME or agonist treatment. Our results showed the unique potential of MR-356 to treat several HFpEF-like features including cardiac hypertrophy, fibrosis, capillary rarefaction, and pulmonary congestion. MR-356 improved cardiac performance by improving diastolic function, global longitudinal strain (GLS), and exercise capacity. Importantly, the increased expression of cardiac pro-brain natriuretic peptide (pro-BNP), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) was restored to normal levels suggesting that MR-356 reduced myocardial stress associated with metabolic inflammation in HFpEF. Thus, agonists of GHRH may be an effective therapeutic strategy for the treatment of cardiometabolic HFpEF phenotype.

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The Endothelial Dysfunction Could Be a Cause of Heart Failure with Preserved Ejection Fraction Development in a Rat Model

Cited by 7 publications

References 36 publications

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry

Vasorelaxant Effect of Moroccan Cannabis sativa Threshing Residues on Rat Mesenteric Arterial Bed is Endothelium and Muscarinic Receptors Dependent

Efficacy of a Growth Hormone-Releasing Hormone Agonist in a Murine Model of Cardiometabolic Heart Failure with Preserved Ejection Fraction

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