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Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy ( = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to , whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of in CMs, caused by infection with an adenovirus encoding (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; = 10-16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 () under PE stimulation ( = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches.
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http://dx.doi.org/10.3390/ijms25010401 | DOI Listing |
BMC Public Health
December 2024
Center for Regenerative and Reconstructive Medicine, Med-X Institute of Western China Science and Technology Innovation Harbour, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
Although many studies have reported the relationship between female hormone intake and cardiovascular disease (CVD) development, their association has not been fully elucidated and defined, based on data from the Third National Health and Nutrition Examination Survey intending to assess the health and nutritional status of non-institutionalized children and adults in the United States. This study examined the relationship between female hormone intake and coronary artery disease (CVD) development in 38,745 women, averaging 38.10 ± 12.
View Article and Find Full Text PDFBackground: Oral treatment with the exogenous ketone body 3-hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4 hours. Treatment with (R)-1,3-butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.
Methods And Results: This was a randomized, single-blind, placebo-controlled, crossover study.
J Am Heart Assoc
December 2024
Smith Center for Outcomes Research in Cardiology, Division of Cardiovascular Medicine, Department of Medicine Beth Israel Deaconess Medical Center Boston MA USA.
Background: Transcatheter edge-to-edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient-centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1- and 2-year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.
View Article and Find Full Text PDFBackground: This real-world evidence study compared risks of cardiovascular events in hospital settings among patients with chronic kidney disease (CKD) with and without hyperkalemia.
Methods And Results: Adults with CKD stages 3b/4 with and without hyperkalemia were identified from Optum's deidentified Market Clarity Data (January 2016-August 2022). Patients with hyperkalemia were exact and propensity score matched to patients without hyperkalemia.
J Am Heart Assoc
December 2024
Arbor Research Collaborative for Health Ann Arbor MI USA.
Background: People with kidney failure have a high risk of cardiovascular morbidity/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial.
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