What question did this study set out to answer?

This research evaluates how doxorubicin affects endothelial progenitor cell (EPC) regulation in cardiomyopathy.

January 10, 2026Turkish computational and theoretical chemistry/Turkish computational and theoretical chemistry :0 citationsOpen Access

Impact of Endothelial Cell Repair Mechanisms on Doxorubicin-Induced Cardiomyopathy: Exploring Molecular Docking and Simulation of Angiogenic Factors

SRSumathi RamasamyKalasalingam Academy of Research and Education JKJ. KanimozhiKalasalingam Academy of Research and Education SASankarganesh ArunachalamChrist University

Key Result

Doxorubicin restricts CXCR4 receptor activity and impairs SDF1 signaling, leading to decreased cardiac endothelial progenitor cell regulation of angiogenesis.

Key Points

This research evaluates how doxorubicin affects endothelial progenitor cell (EPC) regulation in cardiomyopathy.
In silico molecular docking studies
Simulation of SDF1/CXCR4 pathway
Assessment of binding interactions with VEGFR1
Analysis of downstream signaling effects
Doxorubicin binds to SDF1 and CXCR4, reducing their activity.
Inhibition of receptor functions occurs at critical binding sites.
Disruption of angiogenic signaling pathways leads to metabolic chaos.

Structured PICO

Population

In silico molecular docking and simulation models of angiogenic factors (SDF-1, CXCR4, VEGFR1, VEGFR2, ANGPT1, SHIP2)

Intervention

Doxorubicin (in silico molecular docking and 50 ns molecular dynamic simulation)

Outcome

Molecular docking interactions and binding affinities (kcal/mol) of doxorubicin with target proteinssurrogate

In silico modeling suggests doxorubicin may induce cardiomyopathy by directly binding to and inhibiting key angiogenic receptors like CXCR4 and VEGFR1/2, thereby impairing endothelial progenitor cell-mediated vascular repair.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Doxorubicin (Dox), despite being an effective anti-cancer drug, also causes cytotoxicity to non-cancerous tissues. ECs are highly abundant in the heart; thus, endothelial dysfunction is a major cause of doxorubicin-induced cardiomyopathy. The release of EPCs triggered by endothelial dysfunction, participates in the growth of new blood vessels and the repair of damaged endothelium to promote repair mechanism. The current study aimed to evaluate the effects of doxorubicin on SDF1/CXCR4 pathway via in silico molecular docking and simulation studies. Remarkably, heparin binding site of SDF1at LEU: 29 might be preoccupied by doxorubicin leads to poor expression because SDF1 activity heavily depends on its binding sites. On the other hand, active sites of CXCR4 at ASP: 171 and GLU: 288 also engaged by dox, leading to the assumption that doxorubicin restrict the receptor activity. Additionally, the interaction of doxorubicin at the proton acceptor site and ATP binding sites of VEGFR1, including ASP: 1022, GLY: 836, ALE: 837 and PHE: 838, suppresses the function of the receptor in the MAPK1/ERK2 and AKT1 signaling cascades. The co-expressing factor involved in SDF1/CXCR4 like VEGFR2, ANGPT1 and SHIP2 were also affected by specific amino acid interactions. This induces alterations in several vital biochemical pathways, leading to metabolic chaos. Taken together, we hypothesize that doxorubicin-mediated functional inactivity of SDF1 via its receptor CXCR4 and VEGFR1 impaired the cardiac EPCs regulation on angiogenesis and vascularization.

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