Optimal reactive oxygen species concentration and p38 MAP kinase are required for coronary collateral growth.
*Collateral Circulation/drug effects; *Coronary Circulation/drug effects; *MAP Kinase Signaling System/drug effects; Acetophenones/pharmacology; Animal; Animals; Blood Flow Velocity; Cells; Coronary Vessels/surgery; Cultured; Disease Models; Ditiocarb/pharmacology; Endothelial Cells/drug effects/enzymology/*metabolism; Enzyme Inhibitors/pharmacology; Humans; Imidazoles/pharmacology; Inbred WKY; Ligation; Male; Myocardial Reperfusion Injury/enzymology/metabolism/*physiopathology; NADPH Oxidases/antagonists & inhibitors/metabolism; Neovascularization; Onium Compounds/pharmacology; Oxygenases/antagonists & inhibitors/metabolism; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism; Physiologic; Pyridines/pharmacology; Rats; Reactive Oxygen Species/*metabolism; Superoxide Dismutase/antagonists & inhibitors/metabolism; Vascular Endothelial Growth Factor A/metabolism
Reactive oxygen species (ROS) are implicated in coronary collateral growth (CCG). We evaluated the requirement for ROS in human coronary artery endothelial cell (HCAEC) tube formation, CCG in vivo, and signaling (p38 MAP kinase) by which ROS may stimulate vascular growth. The flavin-containing oxidase inhibitor diphenyleneiodonium (DPI) or the superoxide dismutase inhibitor diethyldithiocarbamate (DETC) blocked vascular endothelial growth factor-induced HCAEC tube formation in Matrigel. We assessed the effect of DPI and DETC on CCG in a rat model of repetitive ischemia (RI) (40 s left anterior descending coronary artery occlusion every 20 min for 2 h 20 min, 3 times/day, 10 days). DPI or DETC was given intraperitoneally, or the NAD(P)H oxidase inhibitor apocynin was given in drinking water. Collateral-dependent flow (measured by using microspheres) was expressed as a ratio of normal and ischemic zone flows. In sham-operated rats, collateral flow in the ischemic zone was 18 +/- 6% of normal zone; in the RI group, collateral flow in the ischemic zone was 83 +/- 5% of normal zone. DPI prevented the increase in collateral flow after RI (25 +/- 4% of normal zone). Similar results were obtained with apocynin following RI (32 +/- 7% of that in the normal zone). DETC achieved similar results (collateral flow after RI was 21 +/- 2% of normal zone). DPI and DETC blocked RI-induced p38 MAP kinase activation in response to vascular endothelial growth factor and RI. These results demonstrate a requirement for optimal ROS concentration in HCAEC tube formation, CCG, and p38 MAP kinase activation. p38 MAP kinase inhibition prevented HCAEC tube formation and partially blocked RI-induced CCG (42 +/- 7% of normal zone flow), indicating that p38 MAP kinase is a critical signaling mediator of CCG.
Rocic Petra; Kolz Christopher; Reed Ryan; Potter Barry; Chilian William M
American journal of physiology. Heart and circulatory physiology
2007
2007-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpheart.01330.2006" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.01330.2006</a>
Injury models to study cardiac remodeling in the mouse: myocardial infarction and ischemia-reperfusion.
*Ventricular Remodeling; Animal; Animals; Cardiovascular Surgical Procedures; Coronary Vessels/surgery; Disease Models; Ligation; Mice; Myocardial Infarction/*etiology/*pathology; Myocardial Reperfusion Injury/*etiology/*pathology; Perfusion/methods; Wound Healing
Deep tissue wound healing requires a complex sequence of several factors working in unison to repair the organ at risk. Myocardial infarction (MI) is particularly complex due to several local and systemic factors mediating the repair process within the heart. The wound healing process during this time is critical-the cardiac myocytes are at risk of apoptotic cell death, autophagy, and necrosis. During the early remodeling period, the fibroblasts and myofibroblasts play critical roles in infarct scar formation, a process that is greatly influenced by a robust inflammatory response. Construction of the infarct scar is a "necessary evil" that helps to limit expansion of the infarction; however, the collagen and matrix deposition will often spread to the healthy areas of the heart, causing reactive fibrosis in areas remote from the original damage. This chapter outlines in detail the procedures for two myocardial infarction injury models as well as how to quantify the size of the experimentally induced injury. These procedures are critical to the development of in vivo approaches to study myocardial injury, particularly for use in knockout and transgenic mice.
Luther Daniel J; Thodeti Charles K; Meszaros J Gary
Methods in molecular biology (Clifton, N.J.)
2013
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/978-1-62703-505-7_19" target="_blank" rel="noreferrer noopener">10.1007/978-1-62703-505-7_19</a>