| Title |
Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage
|
|---|---|
| Published in |
Basic Research in Cardiology, April 2016
|
| DOI | 10.1007/s00395-016-0547-4 |
| Pubmed ID | |
| Authors |
Giacinta Guarini, Takahiko Kiyooka, Vahagn Ohanyan, Yuh Fen Pung, Mario Marzilli, Yeong Renn Chen, Chwen Lih Chen, Patrick T. Kang, James P. Hardwick, Christopher L. Kolz, Liya Yin, Glenn L. Wilson, Inna Shokolenko, James G. Dobson, Richard Fenton, William M. Chilian |
| Abstract |
Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process. |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 4% |
| Unknown | 24 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 28% |
| Student > Doctoral Student | 3 | 12% |
| Researcher | 3 | 12% |
| Other | 2 | 8% |
| Student > Bachelor | 2 | 8% |
| Other | 5 | 20% |
| Unknown | 3 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 24% |
| Biochemistry, Genetics and Molecular Biology | 5 | 20% |
| Agricultural and Biological Sciences | 4 | 16% |
| Unspecified | 2 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Other | 4 | 16% |
| Unknown | 3 | 12% |
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 24 May 2017.
All research outputs
#15,462,982
of 22,977,819 outputs
Outputs from Basic Research in Cardiology
#451
of 649 outputs
Outputs of similar age
#180,952
of 300,798 outputs
Outputs of similar age from Basic Research in Cardiology
#6
of 12 outputs
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So far Altmetric has tracked 649 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
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