Introduction: The present study examined the effect of C-type natriuretic peptide (CNP) and biomechanical signals on anabolic and catabolic activities in chondrocyte/agarose constructs.
Methods: Natriuretic peptide (Npr) 2 and 3 expression were compared in non-diseased (grade 0/1) and diseased (grade IV) human cartilage by immunofluoresence microscopy and western blotting. In separate experiments, constructs were cultured under free-swelling conditions or subjected to dynamic compression with CNP, interleukin-1β (IL-1β), the Npr2 antagonist P19 or the Npr3 agonist cANF⁴⁻²³. Nitric oxide (NO) production, prostaglandin E₂ (PGE₂) release, glycosaminoglycan (GAG) synthesis and CNP concentration were quantified using biochemical assays. Gene expression of Npr2, Npr3, CNP, aggrecan and collagen type II were assessed by real-time qPCR. Two-way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse the data.
Results: The present study demonstrates increased expression of natriuretic peptide receptors in diseased or older cartilage (age 70) when compared to non-diseased tissue (age 60) which showed minimal expression. There was strong parallelism in the actions of CNP on cGMP induction resulting in enhanced GAG synthesis and reduction of NO and PGE₂ release induced by IL-1β. Inhibition of Npr2 with P19 maintained catabolic activities whilst specific agonism of Npr3 with cANF⁴⁻²³ had the opposite effect and reduced NO and PGE₂ release. Co-stimulation with CNP and dynamic compression enhanced anabolic activities and inhibited catabolic effects induced by IL-1β. The presence of CNP and the Npr2 antagonist abolished the anabolic response to mechanical loading and prevented loading-induced inhibition of NO and PGE₂ release. In contrast, the presence of the Npr3 agonist had the opposite effect and increased GAG synthesis and cGMP levels in response to mechanical loading and reduced NO and PGE₂ release comparable to control samples. In addition, CNP concentration and natriuretic peptide receptor expression were increased with dynamic compression.
Conclusions: Mechanical loading mediates endogenous CNP release leading to increased natriuretic peptide signalling. The loading-induced CNP/Npr2/cGMP signalling route mediates anabolic events and prevents catabolic activities induced by IL-1β. The CNP pathway therefore represents a potentially chondroprotective intervention for patients with OA, particularly when combined with physiotherapeutic approaches to stimulate biomechanical signals.
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http://dx.doi.org/10.1186/ar4253 | DOI Listing |
Int J Gen Med
December 2024
Department of Cardiology, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161000, People's Republic of China.
Objective: To retrospectively compare the efficacy of Sacubitril/Valsartan and Benazepril in the treatment of heart failure in patients following acute myocardial infarction.
Methods: A retrospective analysis of clinical data was conducted for 103 patients with heart failure following acute myocardial infarction admitted to our hospital from January 2021 to January 2024. All patients met complete inclusion and exclusion criteria.
ESC Heart Fail
December 2024
Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio, USA.
Aims: The interstitial space is the major compartment in which the excess fluid is located, forming peripheral congestion in acute decompensated heart failure (ADHF). The lymphatic system is responsible for the constant drainage of the compartment. In ADHF, the inefficiency of this system causes extravascular fluid accumulation, underscoring the crucial role of lymphatic system failure in ADHF's pathophysiology.
View Article and Find Full Text PDFESC Heart Fail
December 2024
Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.
Aims: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).
View Article and Find Full Text PDFBMC Cardiovasc Disord
December 2024
Department of cardiovascular medicine, Chengdu Seventh People's Hospital, No.1188 Shuangxing Avenue, Chengdu city, 610200, Sichuan Province, China.
Background: Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge, especially in older patients with HT. This study aimed to identify the factors influencing HFpEF occurrence in elderly patients with HT.
Methods: Elderly patients with HT were categorized into two groups: no HFpEF group and HFpEF group based on HFpEF diagnosis.
Objective: To validate the use of brain-type natriuretic peptide (BNP) for detecting and monitoring cardiac dysfunction in captive chimpanzees (Pan troglodytes).
Methods: We analyzed cross-sectional (N = 175) and longitudinal (N = 76) BNP, echocardiogram, ECG, and pathology data from living and deceased captive chimpanzees to examine age and sex effects and to assess the usefulness of BNP for detecting cardiovascular disease and predicting mortality. The study period was from July 2010 through October 2024.
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