Related Experiment Video
Updated: May 5, 2026
A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice
Published on: April 16, 2018
KDM3A knockdown regulates COMP, LOX, COL8A1 and ACOT1 genes in myocardial fibrosis
Abrar A Alzhrani1, Mahmood Rasool2, Sajjad Karim2
1Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Insights
This study identifies key genes like COMP, COL8A1, and LOX involved in heart failure development. Overexpression of KDM3A promotes cardiac fibrosis and heart failure by altering these gene expressions.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Genomics
Background:
- Cardiovascular disease (CVD) is a leading cause of mortality in Saudi Arabia.
- Cardiac remodeling is central to heart failure pathophysiology.
- Identifying genes in pathological cardiac remodeling is crucial.
Purpose of the Study:
- To identify critical genes implicated in pathological cardiac remodeling.
- To investigate the role of lysine-specific demethylase 3A (KDM3A) in cardiac fibrosis.
- To explore potential therapeutic targets for heart failure.
Main Methods:
- Analysis of microarray data (GSE120739) from the Gene Expression Omnibus (GEO) database.
- Utilized in-silico tools: GEO2R, Metascape, WebGestalt, and Ingenuity Pathway Analysis (IPA).
- Investigated gene expression changes related to extracellular matrix and fatty acid metabolism pathways.
Main Results:
- Knockdown of KDM3A led to downregulation of extracellular matrix genes (COMP, COL8A1, LOX).
- Acyl-CoA thioesterase 1 (ACOT1) was upregulated under KDM3A knockdown.
- KDM3A overexpression upregulated fibrosis genes (COMP, COL8A1, LOX) and downregulated ACOT1, enhancing cardiac fibrosis and heart failure.
Conclusions:
- COMP, COL8A1, LOX, and ACOT1 are significantly involved in cardiac fibrosis development.
- KDM3A plays a critical role in regulating fibrosis-related genes.
- These genes represent potential biomarkers for heart failure.
Abstract:
Cardiovascular disease (CVD) is one of the main causes of death in Saudi Arabia. Cardiac remodeling plays a critical role in the pathophysiology of heart failure. Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.
More Related Videos
09:16Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
09:29An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice
Published on: July 14, 2023
