Intra-myocardial Delivery of a Novel Thermosensitive Hydrogel Inhibits Post-infarct Heart Failure After Degradation in R
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ORIGINAL ARTICLE
Intra-myocardial Delivery of a Novel Thermosensitive Hydrogel Inhibits Post-infarct Heart Failure After Degradation in Rat Ying Wen 1,2,3 & Xiao-yan Li 1,2 & Ze-yong Li 4 & Meng-long Wang 1,2 & Pan-pan Chen 1,2,5 & Yang Liu 1,2 & Xian-zheng Zhang 4 & Xue-jun Jiang 1,2 Received: 4 August 2019 / Accepted: 25 November 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Whether intra-myocardial delivery of hydrogel can prevent post-infarct heart failure (HF) in a long follow-up period, especially after it is degraded, remains unclear. In this study, Dex-PCL-HEMA/PNIPAAm (DPHP) hydrogel was delivered into peri-infarct myocardium of rat when coronary artery was ligated, while PBS was employed as control. Twelve weeks later, compared with control, left ventricle remodeling was attenuated and cardiac function was preserved; serum brain natriuretic peptide, cardiac aldosterone, and pulmonary congestion were suppressed in hydrogel group. Pro-fibrogenic mRNA increased in infarct area while decreased in remote zone, as well as hypertrophic mRNA. These data proves DPHP hydrogel suppresses ventricular remodeling and HF by promoting fibrotic healing in infarct area and inhibiting reactive fibrosis and hypertrophy in remote zone. Timely intramyocardial hydrogel implantation is an effective strategy to inhibit post-infarct cardiac remodeling and have a long-term beneficial effect even after it has been biodegraded. Keywords Biodegradable hydrogel . Myocardial infarction . Ventricular remodeling . Heart failure
Abbreviations β-MHC Myosin heavy chain beta ANP Atrial natriuretic peptide BNP Brain natriuretic peptide Associate Editor Nicola Smart oversaw the review of this article * Xue-jun Jiang [email protected] 1
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, People’s Republic of China
2
Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China
3
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
4
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, Hubei, People’s Republic of China
5
Present address: People’s Hospital of Fangcheng County, Nanyang, Henan, China
CSA CVF DPHP ECM LAD LV LVEDD LVESD LVFS HF MI NIZ PEG TGF-β1
Cross-sectional area Collagen volume fraction Dex-PCL-HEMA/ PNIPAAm Extracellular matrix Left coronary artery Left ventricle LV end-diastolic diameter LV end-systolic diameter Left ventricular fractional shortening Heart failure Myocardial infarction Non-infarct zone Polyethylene glycol Transforming growth factor beta1
Introduction Myocardial infarction (MI), caused by irreversible necrosis of myocardium due to occlusion in coronary artery, affects annually 805,000 Americans and causes about half patients dying in the entire world within 5 years [1]. Progress in pharmaceutical therapy and percutaneous coronary intervention saves more patients from MI now, however, cannot prevent survivor
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