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KDM3A knockdown regulates COMP, LOX, COL8A1 and ACOT1 genes in myocardial fibrosis



Abrar A. Alzhrani1, Mahmood Rasool2, *, Sajjad Karim2, Ahmed Alhejin1, Absarul Haque3, Mohamed Morsi1, Mohamed Nabil Alama4 & Peter Natesan Pushparaj2



1Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 3King Fahd Medical Research Center, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Cardiology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; *Corresponding Author



Abrar A. Alzhrani - E-mail: abraralzhrani15@gmail.com

Mahmood Rasool - E-mail: mahmoodrasool@yahoo.com, mrahmed1@kau.edu.sa

Sajjad Karim - E-mail: skarim1@kau.edu.sa

Ahmed Alhejin - E-mail: hejingene@gmail.com

Absarul Haque - E-mail: mhaque@kau.edu.sa

Mohamed Morsi - E-mail: mmahmed@kau.edu.sa

Mohamed Nabil Alama - E-mail: dr_nabilalama@yahoo.com

Peter Natesan Pushparaj - E-mail: peter.n.pushparaj@gmail.com


Article Type

Research Article



Received April 1, 2024; Revised April 30, 2024; Accepted April 30, 2024, Published April 30, 2024



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.



Fibrosis, Heart failure, cardiac remodeling, Extracellular matrix, Ferro ptosis.



Alzhrani et al. Bioinformation 20(4): 305-313 (2024)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.