Acta Physiologica 2011; Volume 202, Supplement 685
Scandinavian Physiological Society's Annual Meeting
MITOCHONDRIAL DNA (MTDNA) DAMAGE DURING MYOCARDIAL ISCHEMIA MARKER OR MAKER OF INJURY?
Abstract number: 8.1.23
BLIKSOEN1 M, MARIERO1 LH, OHM1 IK, YNDESTAD1 A, SOLHEIM1 S, SELJEFLOT1 I, EIDE1 L, HAUGEN1 F, RANHEIM1 T, AUKRUST1 P, VAAGE1 J, VALEN1 G, VINGE1 LE
1IEMR, Oslo Univeristy Hospital, Ullevl, Univeristy of Oslo, Kirkeveien 166, 0407 Oslo, Norway; Email: email@example.com
Myocardial injury may activate the innate immune system by activation of nuclear factor kappa B (NFB) via toll-like receptors (TLRs). Mitochondria are evolutionary endosymbiots and mitochondrial DNA (mtDNA) might contain bacterial molecular motifs, potentially causing a TLR9 mediated, NFB-dependent inflammation. We hypothesize that mtDNA is damaged and released during myocardial ischemia-reperfusion injury and evokes an immune response.
Methods and materials:
Blood was sampled for mtDNA extraction from 20 patients with acute myocardial infarction and 10 patients with stable angina pectoris undergoing percutaneous coronary intervention (PCI).
Isolated, perfused hearts were were subjected to global ischemia and reperfusion (n=10). Coronary effluents and hearts were collected for mtDNA extraction and evaluation with real time PCR.
Human embryonic kidney cells (HEK293lucTLR9/elam), stably transfected with TLR9 reporting elam luciferase activity upon NFB activation, were incubated with vehicle, nuclear DNA (nDNA), mtDNA or TLR9 agonist (CpG-DNA) for 24 hours. Luciferase activity was photometrically assessed.
Patients with myocardial infarction had increased release of mtDNA 3 hours after PCI compared to patients with stable angina (p< 0.01). There was a correlation between infarct size (measured by MRI) and mtDNA release (p =0.01). Ischemic-reperfused mouse hearts had evidence of mtDNA damage (p =0.01), and mtDNA was released into the perfusate (p =0.0015). mtDNA and CpG-DNA activated luciferase activity in HEK293lucTLR9/elam cells (p< 0.0001) indicating TLR9 dependent NFB signaling leading to elam expression.
Ischemiareperfusion caused mtDNA damage in the heart and leakage of mtDNA into the circulation. mtDNA stimulated HEK293lucTLR9/elam cells in a NFB dependent manner.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 685 :8.1.23