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Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats

Overview of attention for article published in International Journal of Nanomedicine, May 2017
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Title
Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats
Published in
International Journal of Nanomedicine, May 2017
DOI 10.2147/ijn.s129324
Pubmed ID
Authors

Raul Maranhao, Maria Carolina Guido, Aline Derisio de Lima, Elaine Rufo Tavares, Alyne Franca Marques, Marcelo Dantas Tavares de Melo, Jose Carlos Nicolau, Vera Salemi, Roberto Kalil-Filho

Abstract

Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of commercial MTX were minor, and did not improve LV function or infarction size. Both treatments did not induce any toxicity. The remarkable improvement in heart function and reduction in infarction size achieved by LDE-MTX supports future clinical trials.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 4%
Unknown 23 96%

Demographic breakdown

Readers by professional status Count As %
Other 4 17%
Student > Bachelor 4 17%
Researcher 3 13%
Student > Master 2 8%
Student > Ph. D. Student 2 8%
Other 3 13%
Unknown 6 25%
Readers by discipline Count As %
Medicine and Dentistry 7 29%
Biochemistry, Genetics and Molecular Biology 2 8%
Immunology and Microbiology 2 8%
Agricultural and Biological Sciences 1 4%
Nursing and Health Professions 1 4%
Other 2 8%
Unknown 9 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 May 2017.
All research outputs
#14,478,437
of 16,416,813 outputs
Outputs from International Journal of Nanomedicine
#2,589
of 3,027 outputs
Outputs of similar age
#228,961
of 269,749 outputs
Outputs of similar age from International Journal of Nanomedicine
#55
of 72 outputs
Altmetric has tracked 16,416,813 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,027 research outputs from this source. They receive a mean Attention Score of 3.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 269,749 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 72 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.