Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta.
Dimitra M KarageorgiadiDiamantis I TsilimigrasPlatonas SelemenakisVassiliki VlachouAnne-Lise DelasticMaria RodiDanai ChatziathanasiouKonstantinos SavvatakisNikolaos AntoniouAikaterini C DeliAlexandros PapalamprosKonstantinos A FilisAthanasia MouzakiAnastasia VarvarigouGeorge ZografosVassilis G GorgoulisIoannis S PaterasFragiska SigalaPublished in: Scientific reports (2020)
Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context.
Keyphrases
- oxidative stress
- ischemia reperfusion injury
- dna damage
- aortic valve
- abdominal aortic aneurysm
- heart failure
- pulmonary artery
- transforming growth factor
- atrial fibrillation
- left ventricular
- aortic dissection
- patients undergoing
- lymph node
- cardiac surgery
- single cell
- drug induced
- cancer therapy
- pulmonary arterial hypertension
- high glucose
- signaling pathway
- dna repair
- endothelial cells