| Title |
Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction
|
|---|---|
| Published in |
Basic Research in Cardiology, September 2017
|
| DOI | 10.1007/s00395-017-0646-x |
| Pubmed ID | |
| Authors |
Nick J. R. Blackburn, Branka Vulesevic, Brian McNeill, Cagla Eren Cimenci, Ali Ahmadi, Mayte Gonzalez-Gomez, Aleksandra Ostojic, Zhiyuan Zhong, Michael Brownlee, Paul J. Beisswenger, Ross W. Milne, Erik J. Suuronen |
| Abstract |
Advanced glycation end-products (AGEs) have been associated with poorer outcomes after myocardial infarction (MI), and linked with heart failure. Methylglyoxal (MG) is considered the most important AGE precursor, but its role in MI is unknown. In this study, we investigated the involvement of MG-derived AGEs (MG-AGEs) in MI using transgenic mice that over-express the MG-metabolizing enzyme glyoxalase-1 (GLO1). MI was induced in GLO1 mice and wild-type (WT) littermates. At 6 h post-MI, mass spectrometry revealed that MG-H1 (a principal MG-AGE) was increased in the hearts of WT mice, and immunohistochemistry demonstrated that this persisted for 4 weeks. GLO1 over-expression reduced MG-AGE levels at 6 h and 4 weeks, and GLO1 mice exhibited superior cardiac function at 4 weeks post-MI compared to WT mice. Immunohistochemistry revealed greater vascular density and reduced cardiomyocyte apoptosis in GLO1 vs. WT mice. The recruitment of c-kit(+) cells and their incorporation into the vasculature (c-kit(+)CD31(+) cells) was higher in the infarcted myocardium of GLO1 mice. MG-AGEs appeared to accumulate in type I collagen surrounding arterioles, prompting investigation in vitro. In culture, the interaction of angiogenic bone marrow cells with MG-modified collagen resulted in reduced cell adhesion, increased susceptibility to apoptosis, fewer progenitor cells, and reduced angiogenic potential. This study reveals that MG-AGEs are produced post-MI and identifies a causative role for their accumulation in the cellular changes, adverse remodeling and functional loss of the heart after MI. MG may represent a novel target for preventing damage and improving function of the infarcted heart. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Bolivia, Plurinational State of | 1 | 25% |
| Japan | 1 | 25% |
| Canada | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 52 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 13% |
| Other | 5 | 10% |
| Student > Postgraduate | 5 | 10% |
| Student > Bachelor | 4 | 8% |
| Student > Master | 4 | 8% |
| Other | 9 | 17% |
| Unknown | 18 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 17% |
| Medicine and Dentistry | 5 | 10% |
| Materials Science | 3 | 6% |
| Agricultural and Biological Sciences | 3 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Other | 9 | 17% |
| Unknown | 21 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 21 August 2023.
All research outputs
#14,261,021
of 24,837,702 outputs
Outputs from Basic Research in Cardiology
#445
of 706 outputs
Outputs of similar age
#155,945
of 321,466 outputs
Outputs of similar age from Basic Research in Cardiology
#5
of 8 outputs
Altmetric has tracked 24,837,702 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 706 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
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