Journal article
Effects of milrinone on inflammatory response-related gene expressions in cultured rat cardiomyocytes
Journal of Biomedical Research, v 33(4), pp 258-263
2019
PMID: 30449737
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Congestive heart failure (CHF) is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion. Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure. Milrinone is a phosphodiesterase. inhibitor and used most commonly for inotropic effect. The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF, and concluded that long-term therapy with milrinone increased morbidity and mortality among patients with advanced CHF. Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways. Hence, we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes, thus leading to adverse clinical outcomes. We used rat cardiomyocyte cell line H9C2 and studied the impact of exposing cardiomyocytes to milrinone (10 mu mol/L) for 24 hours on inflammatory gene expressions. RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay (41 000 genes). The following changes in inflammatory response-related gene expressions were discovered. Genes with increased expressions included: THBS2 (+ 9.98), MMP2 (+3.47), DDIT3 (+2.39), and ADORA3 (+3.5). Genes with decreased expressions were: SPP1 (-5.28) and CD14 (-2.05). We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes. However, further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.
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Details
- Title
- Effects of milrinone on inflammatory response-related gene expressions in cultured rat cardiomyocytes
- Creators
- Archana G. Venakatesh - Drexel Univ, Hahnemann Univ Hosp, Dept Anesthesiol & Perioperat Med, Coll Med, 245 N 15th St,MS 310, Philadelphia, PA 19102 USAJohann J. Mathew - Drexel Univ, Hahnemann Univ Hosp, Dept Anesthesiol & Perioperat Med, Coll Med, 245 N 15th St,MS 310, Philadelphia, PA 19102 USAScott Coleman - Drexel Univ, Hahnemann Univ Hosp, Dept Anesthesiol & Perioperat Med, Coll Med, 245 N 15th St,MS 310, Philadelphia, PA 19102 USALongqiu Yang - Huangshi Central HospitalGeoffrey L. Liu - Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Genom Diagnost,Perelman Sch Med, Philadelphia, PA 19104 USAMarilyn M. Li - Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Genom Diagnost,Perelman Sch Med, Philadelphia, PA 19104 USAHenry Liu - Drexel Univ, Hahnemann Univ Hosp, Dept Anesthesiol & Perioperat Med, Coll Med, 245 N 15th St,MS 310, Philadelphia, PA 19102 USA
- Publication Details
- Journal of Biomedical Research, v 33(4), pp 258-263
- Publisher
- NANJING MEDICAL UNIV; NANJING
- Number of pages
- 5
- Grant note
- This study was fully supported by an internal funding from the Department of Anesthesiology & Perioperative Medicine to Dr. Henry Liu. A portion of the study was presented to Drexel Discovery Day as an abstract.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Anesthesiology and Perioperative Medicine
- Web of Science ID
- WOS:000510144500006
- Scopus ID
- 2-s2.0-85072997907
- Other Identifier
- 991021860814904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental