AI Article Synopsis
- Cardiac aging leads to changes like stiffening and fibrosis, which increase heart disease risk.
- The RAGE receptor plays a significant role in these age-related cardiac changes, and RAGE knockout mice exhibit accelerated heart dimension changes and fibrosis as they age.
- The study analyzed heart gene expression at different ages in RAGE knockout and wild-type mice, revealing specific gene alterations linked to immune responses and cardiac stress as the mice aged.
Article Abstract
Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout () mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female and C57BL/6N (WT) mice. By comparing Young, MA, and Old versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569842 | PMC |
| http://dx.doi.org/10.3390/ijms231911130 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Renal tubular S100A7a impairs fatty acid oxidation and exacerbates renal fibrosis via both intracellular and extracellular pathway.
Biochim Biophys Acta Mol Basis Dis
January 2025
State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Biobank of Peking University First Hospital, Peking University First Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Peking University, Beijing 100034, China. Electronic address:
A couple of S100 family proteins (S100s) have been reported to exert pro-inflammatory functions in the progression of renal fibrosis (RF). Unlike some S100s which are expressed by both epithelial and stromal inflammatory cells, S100A7 is restricted expressed in epithelium. Persistent S100A7 expression occurs in some invasive carcinomas and is associated with poor prognostic factors.
View Article and Find Full Text PDFAn anti-RAGE chimeric antibody alleviates CCl-induced liver fibrosis via RAGE/NF-kB pathway in mice.
Biomed Pharmacother
December 2024
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 201100, China. Electronic address:
Liver fibrosis is a progressive condition characterized by excessive deposition of extracellular matrix components, leading to organ dysfunction. Chronic inflammation and activation of hepatic stellate cells (HSCs) are two dominant events in all stages of fibrosis development. The receptor for advanced glycation end products (RAGE) pathway is involved in modulating liver injury and fibrosis, and preventing it, or deletion of Ager gene can protect the liver against fibrosis progression.
View Article and Find Full Text PDFModulation of persistent bladder pain in mice: The role of macrophage migration inhibitory factor, high mobility group box-1, and downstream signaling pathways.
Bladder (San Franc)
October 2024
Lexington VA Health Care System, Research and Development, Lexington, KY, USA.
Background: Repeated intravesical activation of protease-activated receptor-4 (PAR4) serves as a model of persistent bladder hyperalgesia (BHA) in mice, which lasts several days after the final stimulus. Spinal macrophage migration inhibitory factor (MIF) and high mobility group box 1 (HMGB1) are critical mediators in the persistence of BHA.
Objective: We aimed to identify effective systemic treatments for persistent BHA using antagonists or transgenic deletions.
Assessment of cardiac and skeletal muscle metabolites using H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.
NMR Biomed
January 2025
Department of Radiology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice.
View Article and Find Full Text PDFROLE OF CASPASE-1/CASPASE-11-HMGB1-RAGE/TLR4 SIGNALING IN THE EXACERBATION OF EXTRAPULMONARY SEPSIS INDUCED LUNG INJURY BY MECHANICAL VENTILATION.
Shock
September 2024
Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
Background: Mechanical ventilation (MV) is a clinically important measure for respiratory support in critically ill patients. Although moderate tidal volume MV does not cause lung injury, it can further exacerbate lung injury in pathological state such as sepsis. This pathological process is known as the 'two-hit' theory, whereby an initial lung injury (e.
View Article and Find Full Text PDFWant 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!