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Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction

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Abstract

Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days. SRLX30 did not reduce early myocardial fibrosis but reduced myocardial levels of sST2 and galectin-3. No significant effects were observed with SRLX10 treatment. A significant correlation was observed between plasma levels of serelaxin and effect measures. The results suggest serelaxin has a protective effect in early processes of cardiac remodeling after AMI.

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Abbreviations

AMI:

Acute myocardial infarction

α-SMA:

Alpha smooth muscle actin

GADPH:

Glyceraldehyde 3-phosphate dehydrogenase

IL:

Interleukin

LVEF:

Left ventricle ejection fraction

MCP-1:

Monocyte chemoattractant protein 1

MMP:

Matrix metalloproteinase

RT-PCR:

Reverse transcription polymerase chain reaction

sST2:

Soluble isoform of suppression of tumorigenicity 2

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

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Author information

Authors and Affiliations

  1. Instituto Murciano de Investigación Biomédica (IMIB), Facultad de Medicina, University of Murcia, Murcia, Spain

    Jesus Sanchez-Mas, Antonio Lax, Mari C. Asensio-Lopez, Angela Soriano-Filiu & Domingo A. Pascual-Figal

  2. Departamento de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Moncada, Spain

    Jesus Sanchez-Mas

  3. Pathological Anatomy Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

    Miriam Lencina

  4. Veterinary Teaching Hospital, Veterinary Medicine and Surgery Department, University of Murcia, Murcia, Spain

    Maria J Fernandez-del Palacio

  5. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Rudolf A. de Boer

  6. Cardiology Department, Hospital Universitario Virgen de la Arrixaca, LAIB, Room 2.52, Av. Buenavista s/n, 30120, Murcia, Spain

    Domingo A. Pascual-Figal

  7. CIBER in Cardiovascular Diseases (CIBERCV), Madrid, Spain

    Domingo A. Pascual-Figal

Authors
  1. Jesus Sanchez-Mas
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  2. Antonio Lax
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  3. Mari C. Asensio-Lopez
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  4. Miriam Lencina
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  5. Maria J Fernandez-del Palacio
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  6. Angela Soriano-Filiu
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  7. Rudolf A. de Boer
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  8. Domingo A. Pascual-Figal
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Corresponding author

Correspondence to Domingo A. Pascual-Figal.

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Clinical Relevance

The intravenous infusion of serelaxin for 72 h after acute myocardial infarction might have a favorable effect on early processes of myocardial remodeling, in a dose-dependent manner.

Funding

This study was supported by a grant from Novartis (Switzerland) and was fully performed in the “Instituto Murciano de Investigación Biomética (IMIB),” Universidad de Murcia (Murcia, Spain). This study was partly supported by a grant from the Instituto de Salud Carlos III, Madrid, Spain (PI14/01637). Dr. Lax was a recipient of a research fellowship from the Instituto de Salud Carlos III, Madrid, Spain (CD13/00032). Dr. Pascual Figal was a recipient of a Research Intensification Programme from the Instituto de Salud Carlos III (ISCIII), Madrid, Spain (INT 15/00108 and 16/00172).

Conflict of Interest

Dr. Pascual-Figal and Dr. de Boer received speaker fees from Novartis. All other authors report no conflicts of interest.

Human and Animal Rights and Informed Consent

No human studies were carried out by the authors for this article.

Additional information

Associate Editor Saptarsi Haldar oversaw the review of this article.

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Sanchez-Mas, J., Lax, A., Asensio-Lopez, M.C. et al. Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction. J. of Cardiovasc. Trans. Res. 10, 460–469 (2017). https://doi.org/10.1007/s12265-017-9761-1

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  • DOI: https://doi.org/10.1007/s12265-017-9761-1

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