| Title |
The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway
|
|---|---|
| Published in |
Cardiovascular Drugs and Therapy, March 2018
|
| DOI | 10.1007/s10557-018-6781-2 |
| Pubmed ID | |
| Authors |
Helison Do Carmo, Sapna Arjun, Orlando Petrucci, Derek M Yellon, Sean M Davidson |
| Abstract |
Protecting the heart from ischaemia-reperfusion (IR) injury is a major goal in patients presenting with an acute myocardial infarction. Pyroptosis is a novel form of cell death in which caspase 1 is activated and cleaves interleukin 1β. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also clinically available. It has been shown to be protective against acute IR in vivo rat model, and therefore might be a promising possibility for future cardioprotective therapy. However, it is not known whether protection by VX-765 involves the reperfusion injury salvage kinase (RISK) pathway. We therefore investigated whether VX-765 protects the isolated, perfused rat heart via the PI3K/Akt pathway and whether protection was additive with ischaemic preconditioning (IPC). Langendorff-perfused rat hearts were subject to ischaemia and reperfusion injury in the presence of 30 μM VX-765, with precedent IPC, or the combination of VX-765 and IPC. VX-765 reduced infarct size (28 vs 48% control; P < 0.05) to a similar extent as IPC (30%; P < 0.05). The PI3 kinase inhibitor, wortmannin, abolished the protective effect of VX-765. Importantly in the model used, we were unable to show additive protection with VX-765 + IPC. The caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 22% |
| Student > Bachelor | 4 | 11% |
| Researcher | 3 | 8% |
| Student > Master | 3 | 8% |
| Lecturer | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 16 | 44% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 25% |
| Biochemistry, Genetics and Molecular Biology | 5 | 14% |
| Agricultural and Biological Sciences | 4 | 11% |
| Veterinary Science and Veterinary Medicine | 1 | 3% |
| Social Sciences | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 15 | 42% |
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 13 April 2018.
All research outputs
#17,937,475
of 23,031,582 outputs
Outputs from Cardiovascular Drugs and Therapy
#539
of 698 outputs
Outputs of similar age
#240,062
of 330,380 outputs
Outputs of similar age from Cardiovascular Drugs and Therapy
#6
of 10 outputs
Altmetric has tracked 23,031,582 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 698 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 20th percentile – i.e., 20% 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 330,380 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.