title: Cell adhesion molecule mediation of myocardial inflammatory responses associated with ventricular pacing.
abstract: Poorly synchronized activation of the ventricles can lead to impairment of normal cardiac structure/function. We reported previously that short term (4 h) left ventricular (LV) pacing-induced ventricular dyskinesis led to an inflammatory response localized to the epicardium. Results from this study demonstrated that neutrophils may play a major role in this inflammatory process. Neutrophil recruitment to a site of injury is a process that is highly dependent on an upregulation of cell adhesion molecules (CAM). The dependence of ventricular dysynchrony-induced inflammatory responses on CAM upregulation has not been explored. To gain further insight, we used a mouse model of LV pacing to evaluate the role of CAM in mediating the inflammatory response associated with ventricular dyskinesis. We first examined the effects of LV pacing in wild-type mice. Results demonstrate that 40 min of LV pacing increases ICAM-1 immunostaining as well as myeloperoxidase activity and tissue oxidative stress by twofold in early-activated myocardium. Matrix metalloproteinase-9 activity also increased in the same region by ∼3.5-fold. To determine the role of CAM, mice null for ICAM-1 or p-selectin were subjected to 40 min LV pacing. Results demonstrate that the inflammatory response seen in the wild-type mice was significantly mitigated in the ICAM-1 and p-selectin null mice. In conclusion, results demonstrate that CAM expression plays a critical role in the triggering of LV pacing-induced inflammation, thus providing evidence of a vascular mechanism underlying this response. The mechanisms that trigger an upregulation of myocardial CAM expression and, therefore, inflammation await further investigation since they suggest a specific involvement of vascular events.
authors.affiliation: Department of Biological Sciences, California State University Los Angeles, 90032, USA. kyamaza@calstatela.edu
authors.forename: Katrina Go
authors.initials: KG
authors.lastname: Yamazaki
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Ihm
authors.forename: Robert L
authors.initials: RL
authors.lastname: Thomas
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004562:Electrocardiography; D004567:Electrodes, Implanted; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000503:physiopathology*; D019007:P-Selectin / Q000235:genetics / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D005978:Glutathione