Circulation research [journal]
- Redox Imaging Using Cardiac Myocyte Specific Transgenic Biosensor Mice. [JOURNAL ARTICLE]
- Circ Res 2016 Aug 23.
Changes in redox potentials of cardiac myocytes are linked to several cardiovascular diseases. Redox alterations are currently mostly described qualitatively using chemical sensors, which however do not allow quantifying redox potentials, lack specificity and the possibility to analyze subcellular domains. Recent advances to quantitatively describe defined redox changes include the application of genetically encoded redox biosensors.Establishment of mouse models, which allow the quantification of the glutathione redox potential (EGSH) in the cytoplasm and the mitochondrial matrix of isolated cardiac myocytes and in Langendorff-perfused hearts based on the use of the redox sensitive GFP2 coupled to the glutaredoxin 1 (Grx1-roGFP2).We generated transgenic mice with cardiac myocyte-restricted expression of Grx1-roGFP2 either targeted to the mitochondrial matrix or the cytoplasm. The response of the roGFP2 towards H2O2, diamide, and dithiothreitol (DTT) was titrated and used to determine the EGSH in isolated cardiac myocytes and in Langendorff-perfused hearts. Distinct EGSH were observed in the cytoplasm and the mitochondrial matrix. Stimulation of the cardiac myocytes with isoprenaline, angiotensin II or exposure to hypoxia/reoxygenation additionally underscored that these compartments responded independently. A compartment-specific response was also observed 3-14 days after myocardial infarction.We introduce redox biosensor mice as a new tool, which allows quantification of defined alterations of EGSH in the cytoplasm and the mitochondrial matrix in cardiac myocytes and can be exploited to answer questions in basic and translational cardiovascular research.
- In Memoriam: Arnold M. Katz, MD: 1932-2016. [Journal Article]
- Circ Res 2016 Apr 15; 118(8):1192-3.
- Time to Give Up on Cardioprotection? A Critical Appraisal of Clinical Studies on Ischemic Pre-, Post-, and Remote Conditioning. [Journal Article, Review]
- Circ Res 2016 Aug 19; 119(5):676-95.
The mortality from acute myocardial infarction (AMI) remains significant, and the prevalence of post-myocardial infarction heart failure is increasing. Therefore, cardioprotection beyond timely reperfusion is needed. Conditioning procedures are the most powerful cardioprotective interventions in animal experiments. However, ischemic preconditioning cannot be used to reduce infarct size in patients with AMI because its occurrence is not predictable; several studies in patients undergoing surgical coronary revascularization report reduced release of creatine kinase and troponin. Ischemic postconditioning reduces infarct size in most, but not all, studies in patients undergoing interventional reperfusion of AMI, but may require direct stenting and exclusion of patients with >6 hours of symptom onset to protect. Remote ischemic conditioning reduces infarct size in patients undergoing interventional reperfusion of AMI, elective percutaneous or surgical coronary revascularization, and other cardiovascular surgery in many, but not in all, studies. Adequate dose-finding phase II studies do not exist. There are only 2 phase III trials, both on remote ischemic conditioning in patients undergoing cardiovascular surgery, both with neutral results in terms of infarct size and clinical outcome, but also both with major problems in trial design. We discuss the difficulties in translation of cardioprotection from animal experiments and proof-of-concept trials to clinical practice. Given that most studies on ischemic postconditioning and all studies on remote ischemic preconditioning in patients with AMI reported reduced infarct size, it would be premature to give up on cardioprotection.
- Trends in NHLBI-Funded Research on Sex Differences in Hypertension. [Journal Article]
- Circ Res 2016 Aug 19; 119(5):591-5.
- Canon Fodder-A Case for Contrarian Science. [Journal Article]
- Circ Res 2016 Aug 19; 119(5):584-6.
- Heart Rate Recovery: Coming Back Full-Circle to the Baroreceptor Reflex. [Editorial]
- Circ Res 2016 Aug 19; 119(5):582-3.
- Inject Me Once and Inject Me Twice. Then Inject Me Once Again. [Editorial]
- Circ Res 2016 Aug 19; 119(5):580-1.
- A Buttery Taste to Vascular Biology: Endothelial Cells Generate and Release γ-Aminobutyric Acid. [Editorial]
- Circ Res 2016 Aug 19; 119(5):577-9.
- Plasticity of Arterial and Venous Endothelial Cell Identity: Some Nerve! [Editorial]
- Circ Res 2016 Aug 19; 119(5):574-6.