Sustained-release Delivery of Prostacyclin Analogue Enhances Bone Marrow-cell Recruitment and Yields Functional Benefits for Acute Myocardial Infarction in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jul 30

PMID 23894446

Citations 12

Authors

Yukiko Imanishi

Shigeru Miyagawa

Satsuki Fukushima

Kazuhiko Ishimaru

Nagako Sougawa

Atsuhiro Saito

Yoshiki Sakai

Yoshiki Sawa

Affiliations

Soon will be listed here.

Abstract

Background: A prostacyclin analogue, ONO-1301, is reported to upregulate beneficial proteins, including stromal cell derived factor-1 (SDF-1). We hypothesized that the sustained-release delivery of ONO-1301 would enhance SDF-1 expression in the acute myocardial infarction (MI) heart and induce bone marrow cells (BMCs) to home to the myocardium, leading to improved cardiac function in mice.

Methods And Results: ONO-1301 significantly upregulated SDF-1 secretion by fibroblasts. BMC migration was greater to ONO-1301-stimulated than unstimulated conditioned medium. This increase was diminished by treating the BMCs with a CXCR4-neutralizing antibody or CXCR4 antagonist (AMD3100). Atelocollagen sheets containing a sustained-release form of ONO-1301 (n = 33) or ONO-1301-free vehicle (n = 48) were implanted on the left ventricular (LV) anterior wall immediately after permanent left-anterior descending artery occlusion in C57BL6/N mice (male, 8-weeks-old). The SDF-1 expression in the infarct border zone was significantly elevated for 1 month in the ONO-1301-treated group. BMC accumulation in the infarcted hearts, detected by in vivo imaging after intravenous injection of labeled BMCs, was enhanced in the ONO-1301-treated hearts. This increase was inhibited by AMD3100. The accumulated BMCs differentiated into capillary structures. The survival rates and cardiac function were significantly improved in the ONO-1301-treated group (fractional area change 23±1%; n = 22) compared to the vehicle group (19±1%; n = 20; P = 0.004). LV anterior wall thinning, expansion of infarction, and fibrosis were lower in the ONO-1301-treated group.

Conclusions: Sustained-release delivery of ONO-1301 promoted BMC recruitment to the acute MI heart via SDF-1/CXCR4 signaling and restored cardiac performance, suggesting a novel mechanism for ONO-1301-mediated acute-MI heart repair.

Citing Articles

Regenerative medicine in cardiovascular disease.

Goto T, Nakamura Y, Ito Y, Miyagawa S Regen Ther. 2024; 26:859-866.

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Enhanced myocardial blood flow in ischemic cardiomyopathy by a slow-release synthetic prostacyclin agonist combined with coronary artery bypass grafting: The first human study in a Phase I/IIa clinical trial.

Kawamura T, Yoshioka D, Kawamura M, Matsuura R, Kawamura A, Misumi Y Front Cardiovasc Med. 2023; 10:1047666.

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Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling.

Shin H, Thakore A, Tada Y, Pedroza A, Ikeda G, Chen I Sci Rep. 2022; 12(1):17605.

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Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart.

Sougawa N, Miyagawa S, Kawamura T, Matsuura R, Harada A, Sakai Y Sci Rep. 2021; 11(1):22243.

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Synthetic Prostacyclin Agonist Attenuates Pressure-Overloaded Cardiac Fibrosis by Inhibiting FMT.

Masada K, Miyagawa S, Sakai Y, Harada A, Kanaya T, Sawa Y Mol Ther Methods Clin Dev. 2020; 19:210-219.

PMID: 33102614 PMC: 7558785. DOI: 10.1016/j.omtm.2020.09.005.

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