Therapeutic strategies for reversing cardiac fibrosis in hearts supported by ventricular assist devices

Kartiga Natarajan; Muthu Kumar Krishnamoorthi; Suresh S. Palaniyandi; Kenichi Watanabe; Henry J. Pownall; Ashrith Guha; Arvind Bhimaraj; Rajarajan A. Thandavarayan

doi:10.1016/j.drudis.2025.104547

Therapeutic strategies for reversing cardiac fibrosis in hearts supported by ventricular assist devices

Kartiga Natarajan, Muthu Kumar Krishnamoorthi, Suresh S. Palaniyandi, Kenichi Watanabe, Henry J. Pownall, Ashrith Guha, Arvind Bhimaraj, Rajarajan A. Thandavarayan

Research output: Contribution to journal › Review article › peer-review

1 Scopus citations

Abstract

Left ventricular assist devices (LVADs) support patients with end-stage heart failure, yet myocardial recovery and device explant remains rare because of persistent cardiac fibrosis. This review examines the integration of molecular mechanisms and highlights therapeutic targets emerging from clinical and preclinical studies, with a focus on mechanisms that differentiate responders from non-responders. Key pathways include extracellular matrix remodeling, fibroblast activation, cellular plasticity, endothelial-to-mesenchymal transition, immune modulation, and post-transcriptional regulation via alternative polyadenylation. Advancing these mechanistic insights could enable biomarker-driven strategies to overcome the current barriers to improving recovery rates in patients supported by LVADs.

Original language	English (US)
Article number	104547
Journal	Drug Discovery Today
Volume	30
Issue number	12
Early online date	Nov 18 2025
DOIs	https://doi.org/10.1016/j.drudis.2025.104547
State	Published - Nov 27 2025

Keywords

alternative polyadenylation
cardiac fibrosis
endothelial-to-mesenchymal transition
extracellular matrix remodeling
left ventricular assist device
myocardial recovery
Animals
Myocardium/pathology
Humans
Fibrosis
Heart Failure/therapy
Heart-Assist Devices

ASJC Scopus subject areas

Pharmacology
Drug Discovery

Divisions

Endocrinology, Diabetes and Metabolism

Access to Document

10.1016/j.drudis.2025.104547

Cite this

@article{a2717a70853145cba28bb5e65a144ff2,

title = "Therapeutic strategies for reversing cardiac fibrosis in hearts supported by ventricular assist devices",

abstract = "Left ventricular assist devices (LVADs) support patients with end-stage heart failure, yet myocardial recovery and device explant remains rare because of persistent cardiac fibrosis. This review examines the integration of molecular mechanisms and highlights therapeutic targets emerging from clinical and preclinical studies, with a focus on mechanisms that differentiate responders from non-responders. Key pathways include extracellular matrix remodeling, fibroblast activation, cellular plasticity, endothelial-to-mesenchymal transition, immune modulation, and post-transcriptional regulation via alternative polyadenylation. Advancing these mechanistic insights could enable biomarker-driven strategies to overcome the current barriers to improving recovery rates in patients supported by LVADs.",

keywords = "alternative polyadenylation, cardiac fibrosis, endothelial-to-mesenchymal transition, extracellular matrix remodeling, left ventricular assist device, myocardial recovery, Animals, Myocardium/pathology, Humans, Fibrosis, Heart Failure/therapy, Heart-Assist Devices",

author = "Kartiga Natarajan and Krishnamoorthi, \{Muthu Kumar\} and Palaniyandi, \{Suresh S.\} and Kenichi Watanabe and Pownall, \{Henry J.\} and Ashrith Guha and Arvind Bhimaraj and Thandavarayan, \{Rajarajan A.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Ltd.",

year = "2025",

month = nov,

day = "27",

doi = "10.1016/j.drudis.2025.104547",

language = "English (US)",

volume = "30",

journal = "Drug Discovery Today",

issn = "1359-6446",

publisher = "Elsevier Ltd",

number = "12",

}

TY - JOUR

T1 - Therapeutic strategies for reversing cardiac fibrosis in hearts supported by ventricular assist devices

AU - Natarajan, Kartiga

AU - Krishnamoorthi, Muthu Kumar

AU - Palaniyandi, Suresh S.

AU - Watanabe, Kenichi

AU - Pownall, Henry J.

AU - Guha, Ashrith

AU - Bhimaraj, Arvind

AU - Thandavarayan, Rajarajan A.

PY - 2025/11/27

Y1 - 2025/11/27

N2 - Left ventricular assist devices (LVADs) support patients with end-stage heart failure, yet myocardial recovery and device explant remains rare because of persistent cardiac fibrosis. This review examines the integration of molecular mechanisms and highlights therapeutic targets emerging from clinical and preclinical studies, with a focus on mechanisms that differentiate responders from non-responders. Key pathways include extracellular matrix remodeling, fibroblast activation, cellular plasticity, endothelial-to-mesenchymal transition, immune modulation, and post-transcriptional regulation via alternative polyadenylation. Advancing these mechanistic insights could enable biomarker-driven strategies to overcome the current barriers to improving recovery rates in patients supported by LVADs.

AB - Left ventricular assist devices (LVADs) support patients with end-stage heart failure, yet myocardial recovery and device explant remains rare because of persistent cardiac fibrosis. This review examines the integration of molecular mechanisms and highlights therapeutic targets emerging from clinical and preclinical studies, with a focus on mechanisms that differentiate responders from non-responders. Key pathways include extracellular matrix remodeling, fibroblast activation, cellular plasticity, endothelial-to-mesenchymal transition, immune modulation, and post-transcriptional regulation via alternative polyadenylation. Advancing these mechanistic insights could enable biomarker-driven strategies to overcome the current barriers to improving recovery rates in patients supported by LVADs.

KW - alternative polyadenylation

KW - cardiac fibrosis

KW - endothelial-to-mesenchymal transition

KW - extracellular matrix remodeling

KW - left ventricular assist device

KW - myocardial recovery

KW - Animals

KW - Myocardium/pathology

KW - Humans

KW - Fibrosis

KW - Heart Failure/therapy

KW - Heart-Assist Devices

UR - https://www.scopus.com/pages/publications/105023573249

UR - https://www.scopus.com/inward/citedby.url?scp=105023573249&partnerID=8YFLogxK

U2 - 10.1016/j.drudis.2025.104547

DO - 10.1016/j.drudis.2025.104547

M3 - Review article

C2 - 41265516

AN - SCOPUS:105023573249

SN - 1359-6446

VL - 30

JO - Drug Discovery Today

JF - Drug Discovery Today

IS - 12

M1 - 104547

ER -

Therapeutic strategies for reversing cardiac fibrosis in hearts supported by ventricular assist devices

Abstract

Keywords

ASJC Scopus subject areas

Divisions

Access to Document

Other files and links

Fingerprint

Cite this