Oxolipidomic characterization of ischemia-reperfusion injury
| dc.contributor.author | Solati, Zahra | |
| dc.contributor.examiningcommittee | Pierce, Grant (Physiology and Pathophysiology) | en_US |
| dc.contributor.examiningcommittee | Aukema, Harold (Food and Human Nutritional Sciences) | en_US |
| dc.contributor.examiningcommittee | Bkaily, Ghassan (Université de Sherbrooke) | en_US |
| dc.contributor.supervisor | Ravandi, Amir (Physiology and Pathophysiology) | en_US |
| dc.date.accessioned | 2021-08-31T11:07:21Z | |
| dc.date.available | 2021-08-31T11:07:21Z | |
| dc.date.copyright | 2021-08-26 | |
| dc.date.issued | 2021 | en_US |
| dc.date.submitted | 2021-08-26T15:23:35Z | en_US |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Hypothesis: Concentrations of bioactive oxidized lipids, such as fragmented oxidized phosphatidylcholines (OxPCs) and oxylipins, will increase significantly following ischemia/reperfusion (I/R) and changes in oxidized lipids concentrations are correlated with markers of tissue injury. Objective: The goal of this thesis was to determine the changes of bioactive oxidized lipids, including OxPCs and oxylipins during I/R. Methods: Kidney I/R was induced in male Sprague–Dawley rats by clamping the left renal pedicle for 45 min followed by reperfusion for either 6h or 24h. For myocardial I/R, blood samples were collected from patients presenting with ST-Elevation Myocardial Infarction STEMI before primary percutaneous coronary intervention (PPCI) (Isch) and at 4 time-points post-PPCI, including 2h (R-2h), 24h (R-24h), 48h (R-48h) and 30 days (R-30d). As controls, blood samples were collected from age-matched patients with non-obstructive coronary artery disease. OxPCs and oxylipins were identified and quantitated using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Result: During renal I/R, total tissue concentrations of fragmented aldehyde-containing OxPCs were significantly elevated at 6h and 24h post-reperfusion compared to sham-operated animals (p<0.05) and their levels were significantly correlated with plasma creatinine levels (r=0.888, p=0.001). In patients with STEMI, total plasma levels of fragmented OxPCs increased significantly during ischemia compared with controls (p<0.05). Their levels remained elevated for 48h after reperfusion and then decreased significantly at 30-day post-MI compared with R-2h and R-24h groups (p<0.05). STEMI patients with an elevated peak of creatine kinase (CK) concentrations had significantly higher ischemic plasma levels of 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-(9-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC) (p<0.05). Plasma concentrations of total docosahexaenoic acid (DHA) derived oxylipins were significantly elevated in the Isch group compared with controls (p<0.001). Moreover, their levels during ischemia were significantly correlated with the peak CK and troponin T(TnT) levels (p<0.05). Univariate receiver operating characteristic (ROC) curve analysis showed that the higher ratio of epoxides to diols during the ischemia could be considered as a potential marker of having a smaller infarct size based on CK levels (AUC= 0.77, p=0.03). Conclusion: We have shown for the first time that bioactive oxidized lipids are produced during I/R and their levels correlate with markers of tissue injury. | en_US |
| dc.description.note | October 2021 | en_US |
| dc.identifier.citation | Solati, Zahra, and Amir Ravandi. "Lipidomics of bioactive lipids in acute coronary syndromes." International journal of molecular sciences 20, no. 5 (2019): 1051. | en_US |
| dc.identifier.citation | Solati Z, Edel AL, Shang Y, O K, Ravandi A. Oxidized phosphatidylcholines are produced in renal ischemia reperfusion injury. PLoS One. 2018 Apr 23;13(4):e0195172. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/35860 | |
| dc.rights | open access | en_US |
| dc.subject | Bioactive lipids | en_US |
| dc.subject | Oxidized phospholipids | en_US |
| dc.subject | Oxylipin | en_US |
| dc.subject | Oxidized phosphatidylcholine | en_US |
| dc.subject | Oxo-lipidomics | en_US |
| dc.subject | Ischemia/reperfusion injury | en_US |
| dc.title | Oxolipidomic characterization of ischemia-reperfusion injury | en_US |
| dc.type | doctoral thesis | en_US |