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- Title
Recombinant Klotho Protein Ameliorates Myocardial Ischemia/Reperfusion Injury by Attenuating Sterile Inflammation.
- Authors
Myung, Jinwoo; Beom, Jin-Ho; Kim, Ju-Hee; Woo, Ji-Sun; Park, Incheol; Chung, Sung-Phil; Chung, Yong-Eun; You, Je-Sung
- Abstract
Currently, no effective therapy and potential target have been elucidated for preventing myocardial ischemia and reperfusion injury (I/R). We hypothesized that the administration of recombinant klotho (rKL) protein could attenuate the sterile inflammation in peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1). This hypothesis was examined using a rat coronary artery ligation model. Rats were divided into sham, sham+ rKL, I/R, and I/R+ rKL groups (n = 5/group). Administration of rKL protein reduced infarct volume and attenuated extracellular release of HMGB1 from peri-infarct tissue after myocardial I/R injury. The administration of rKL protein inhibited the expression of pro-inflammatory cytokines in the peri-infarct regions and significantly attenuated apoptosis and production of intracellular reactive oxygen species by myocardial I/R injury. Klotho treatment significantly reduced the increase in the levels of circulating HMGB1 in blood at 4 h after myocardial ischemia. rKL regulated the levels of inflammation-related proteins. This is the first study to suggest that exogenous administration of rKL exerts myocardial protection effects after I/R injury and provides new mechanistic insights into rKL that can provide the theoretical basis for clinical application of new adjunctive modality for critical care of acute myocardial infarction.
- Subjects
MYOCARDIAL ischemia; REPERFUSION injury; RECOMBINANT proteins; MYOCARDIAL infarction; MYOCARDIAL reperfusion
- Publication
Biomedicines, 2022, Vol 10, Issue 4, p894
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines10040894