Insulin-Like Growth Factor 1 Receptor-Dependent Pathway Drives Epicardial Adipose Tissue Formation After Myocardial Injury

Overview

Journal Circulation

Specialty Cardiology & Vascular Diseases

Date 2016 Nov 3

PMID 27803039

Citations 46

Authors

Lior Zangi

Marcela S Oliveira

Lillian Y Ye

Qing Ma

Nishat Sultana

Yoav Hadas

Elena Chepurko

Daniela Spater

Bin Zhou

Wei Leong Chew

Wataru Ebina

Maryline Abrial

Qing-Dong Wang

William T Pu

Kenneth R Chien

Affiliations

Soon will be listed here.

Abstract

Background: Epicardial adipose tissue volume and coronary artery disease are strongly associated, even after accounting for overall body mass. Despite its pathophysiological significance, the origin and paracrine signaling pathways that regulate epicardial adipose tissue's formation and expansion are unclear.

Methods: We used a novel modified mRNA-based screening approach to probe the effect of individual paracrine factors on epicardial progenitors in the adult heart.

Results: Using 2 independent lineage-tracing strategies in murine models, we show that cells originating from the Wt1 mesothelial lineage, which includes epicardial cells, differentiate into epicardial adipose tissue after myocardial infarction. This differentiation process required Wt1 expression in this lineage and was stimulated by insulin-like growth factor 1 receptor (IGF1R) activation. IGF1R inhibition within this lineage significantly reduced its adipogenic differentiation in the context of exogenous, IGF1-modified mRNA stimulation. Moreover, IGF1R inhibition significantly reduced Wt1 lineage cell differentiation into adipocytes after myocardial infarction.

Conclusions: Our results establish IGF1R signaling as a key pathway that governs epicardial adipose tissue formation in the context of myocardial injury by redirecting the fate of Wt1 lineage cells. Our study also demonstrates the power of modified mRNA -based paracrine factor library screening to dissect signaling pathways that govern progenitor cell activity in homeostasis and disease.

Citing Articles

Potential Application of Modified mRNA in Cardiac Regeneration.

Wang A, Chang Y, Chen K, Loh C Cell Transplant. 2024; 33:9636897241248956.

PMID: 38715279 PMC: 11080755. DOI: 10.1177/09636897241248956.

The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration.

Krauz K, Kempinski M, Janczak P, Momot K, Zarebinski M, Poprawa I Int J Mol Sci. 2024; 25(7).

PMID: 38612394 PMC: 11011833. DOI: 10.3390/ijms25073583.

Modified mRNA Formulation and Stability for Cardiac and Skeletal Muscle Delivery.

Zak M, Kaur K, Yoo J, Kurian A, Adjmi M, Mainkar G Pharmaceutics. 2023; 15(9).

PMID: 37765147 PMC: 10535735. DOI: 10.3390/pharmaceutics15092176.

Nanomaterials for mRNA-based therapeutics: Challenges and opportunities.

Li D, Liu Q, Yang M, Xu H, Zhu M, Zhang Y Bioeng Transl Med. 2023; 8(3):e10492.

PMID: 37206219 PMC: 10189457. DOI: 10.1002/btm2.10492.

The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review.

Kim I, Song B, Lim S, Kim S, Lee S Biology (Basel). 2023; 12(4).

PMID: 37106699 PMC: 10135702. DOI: 10.3390/biology12040498.

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