AI Article Synopsis
- PITX2 and Nkx2.5 are crucial for heart development, with PITX2's absence leading to severe heart defects and embryonic death in mice.
- The study identifies the atrial natriuretic factor (ANF) promoter as a target of PITX2, with PITX2C being the only isoform that activates ANF when teamed with Nkx2.5, while PITX2A's activation is inhibited by Nkx2.5.
- Additionally, Nkx2.5 regulates the procollagen lysyl hydroxylase (PLOD1) promoter, indicating that PITX2 and Nkx2.5 work together to control gene expression essential for heart development.
Article Abstract
PITX2 and Nkx2.5 are two of the earliest known transcriptional markers of vertebrate heart development. Pitx2-/- mice present with severe cardiac malformations and embryonic lethality, demonstrating a role for PITX2 in heart development. However, little is known about the downstream targets of PITX2 in cardiogenesis. We report here that the atrial natriuretic factor (ANF) promoter is a target of PITX2. PITX2A, PITX2B, and PITX2C isoforms differentially activate the ANF promoter. However, only PITX2C can synergistically activate the ANF promoter in the presence of Nkx2.5. We further demonstrate that the procollagen lysyl hydroxylase (PLOD1) promoter is regulated by Nkx2.5. Mechanistically, PITX2C and Nkx2.5 synergistically regulate ANF and PLOD1 expression through binding to their respective DNA elements. Surprisingly, PITX2A activation of the ANF and PLOD1 promoters is repressed by co-transfection of Nkx2.5 in the C3H10T1/2 embryonic fibroblast cell line. Pitx2a and Pitx2c are endogenously expressed in C3H10T1/2 cells, and these cells express factors that differentially regulate PITX2 isoform activities. We provide a new mechanism for the regulation of heart development by PITX2 isoforms through the regulation of ANF and PLOD1 gene expression and Nkx2.5 transcriptional activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M210163200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Coronary heart disease (CHD) and depression frequently co-occur, significantly impacting patient outcomes. However, comprehensive health status assessment tools for this complex population are lacking. This study aimed to develop and validate an explainable machine learning model to evaluate overall health status in patients with comorbid CHD and depression.
View Article and Find Full Text PDFDigital Home-Based Self-Monitoring System for People with Heart Failure: Protocol for Development of SmartHeart and Evaluation of Feasibility and Acceptability.
JMIR Res Protoc
January 2025
School of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition, Deakin University, Burwood, Australia.
Background: Heart failure (HF) is a chronic, progressive condition where the heart cannot pump enough blood to meet the body's needs. In addition to the daily challenges that HF poses, acute exacerbations can lead to costly hospitalizations and increased mortality. High health care costs and the burden of HF have led to the emerging application of new technologies to support people living with HF to stay well while living in the community.
View Article and Find Full Text PDFHemodynamic analysis of left ventricular unloading with Impella versus IABP during VA-ECMO.
Acta Bioeng Biomech
June 2024
1Department of Biomedical Engineering, Hefei University of Technology, Hefei, People's Republic of China.
: The utilization of intra-aortic balloon pump (IABP) and Impella has been suggested as means of left ventricular unloading in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients. This study aimed to assess the local hemodynamic alterations in VA-ECMO patients through simulation analyses. : In this study, a 0D-3D multiscale model was developed, wherein resistance conditions were employed to define the flow-pressure relationship.
View Article and Find Full Text PDFEuropean Society of Cardiology quality indicators for the management of acute coronary syndrome.
Eur Heart J Acute Cardiovasc Care
January 2025
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Background: Closing the evidence-practice gap for the treatment of acute coronary syndrome (ACS) is central to improving quality of care. Under the European Society of Cardiology (ESC) framework, we aimed to develop updated quality indicators (QIs) for the evaluation of quality of care and outcomes for patients with ACS.
Methods: A Working Group of experts including members of the ESC Clinical Practice Guidelines Task Force for ACS, Acute CardioVascular Care Association and European Association of Percutaneous Cardiovascular Interventions followed the ESC methodology for QI development.
Clinical derivation and data simulated validation of rule-out and rule-in algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I assay.
Eur Heart J Acute Cardiovasc Care
January 2025
Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
Background: This prospective, two-centre study derived and validated predictive algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I (hs-cTnI) assay in the emergency department (ED).
Methods: Algorithms for predicting 30-day myocardial infarction type 1 and 2 (MI) and death or non-ST-elevation myocardial infarction (NSTEMI, type 1 and 2) at index admission were developed from a derivation cohort of 1896 patients and validated using a synthetic dataset with nearly 1 million patient cases. Performance was compared to the European Society of Cardiology algorithms for hs-cTnT (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!