Background: Myocardial infarction (MI) is a common and multifactorial disease. To date, causal genes and underlying mechanisms remain largely unknown. Autophagic-lysosomal system, a highly conserved degradative process in cells, has been implicated in lipid metabolism. In this study, we explored the alterations of the autophagic-lysosomal system in patients with acute MI.
Methods: Gene expression of lysosomal associated membrane protein 2 (LAMP-2), a lysosomal marker gene, and microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker gene, in the peripheral leukocytes of MI patients were examined at transcription and protein levels by RT-PCR assay and western blot analysis, respectively.
Results: Compared to age- and sex-matched healthy controls (n=146), levels of LC3 gene expression and LC3-II protein, a cleaved form of LC3 protein, were significantly decreased in MI patients (n=81). LAMP-2 gene expression and protein levels were significantly increased. Decreased LC3 gene expression (OR, 2.150, 95%CI, 1.050-4.405, P=0.036) or increased LAMP-2 gene expression (OR, 3.317, 95%CI, 1.588-6.931, P<0.001) levels were associated with MI.
Conclusions: Our findings indicated that in the peripheral leukocytes of MI patients, autophagy activity is reduced and lysosomal accumulation is increased, which may contribute to the MI pathogenesis. Further genetic analyses of autophagic-lysosomal genes are warranted.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cca.2011.05.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Classification-based pathway analysis using GPNet with novel P-value computation.
Brief Bioinform
November 2024
Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States.
Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks.
View Article and Find Full Text PDFTargeting AXL inhibits the growth and metastasis of prostate cancer in bone.
Clin Cancer Res
January 2025
Stanford University, Palo Alto, CA, United States.
Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.
Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by immunohistochemical staining.
Protocol to boost the robustness and accuracy of spatial transcriptomics algorithms using ensemble techniques.
STAR Protoc
January 2025
Department of Statistics, University of Georgia, 310 Herty Drive, Athens, GA 30602, USA. Electronic address:
Spatial transcriptomics enhances our understanding of cellular organization by mapping gene expression data to precise tissue locations. Here, we present a protocol for using weighted ensemble method for spatial transcriptomics (WEST), which uses ensemble techniques to boost the robustness and accuracy of existing algorithms. We describe steps for preprocessing data, obtaining embeddings from individual algorithms, and ensemble integrating all embeddings as a similarity matrix.
View Article and Find Full Text PDFUndocking of an extensive ciliary network induces proteostasis and cell fate switching resulting in severe primary ciliary dyskinesia.
Sci Transl Med
January 2025
Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Article Synopsis
- Primary ciliary dyskinesia (PCD) is a rare genetic disorder linked to chronic respiratory issues, infertility, and problems with body asymmetry, primarily caused by mutations in the CCDC39 and CCDC40 genes.
- Researchers used advanced techniques to investigate how these genetic variants impact cellular functions beyond just causing cilia to stop moving.
- They discovered that the absence of CCDC39/CCDC40 creates a significant loss of over 90 ciliary structural proteins, leading to cilia dysfunction and other cellular issues, suggesting that gene therapy could potentially offer a new treatment strategy for PCD.
Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.
Sci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
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!