Cell adhesion molecule mediation of myocardial inflammatory responses associated with ventricular pacing

Abstract

Yamazaki KG, Ihm S, Thomas RL, Roth D, Villarreal F. Cell adhesion molecule mediation of myocardial inflammatory responses associated with ventricular pacing. Am J Physiol Heart Circ Physiol 302: H1387-H1393, 2012. First published January 20, 2012 doi:10.1152/ajpheart.00496.2011.-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 ϳ3.5-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. left ventricular pacing; inflammation ABNORMAL ACTIVATION OF THE ventricles has emerged as a major contributor to the pathophysiology of heart failure. Perturbations in the normal sequence of left ventricular (LV) activation can create regions of early and late activation, leading to dysynchronous contraction and areas of dyskinesis (23). It has been shown that poorly synchronized activation of the LV can impair diastolic and systolic function, promote chamber remodeling, and lead to increased morbidity and mortality in patients with heart failure (22).Mechanisms that trigger LV remodeling associated with ventricular dysynchrony are not fully understood. We reported previously the results of a study in which we induced abnormal wall motion (i.e., dyskinesis) on the anterior lateral wall of canine hearts by LV pacing. Results demonstrated that 4 h of epicardial LV pacing triggered increases in myeloperoxidase (MPO) activity, reactive oxygen species (ROS) generation, 92 kDa matrix metalloproteinase (M...

Association Between Vascular Cell Adhesion Molecule 1 and Atrial Fibrillation

“…Although only low levels are expressed on resting endothelium and endocardium, marked upregulation of VCAM-1 is elicited by various stress conditions. In a number of human heart diseases, reactive oxygen species and hemodynamic factors have been shown to enhance cardiac VCAM-1 expression, 12,26 and subsequent cell infiltration and inflammation in heart tissue gives rise to sustained cardiac remodeling, fibrosis, and dysfunction. 4 Accumulating evidence suggests that atrial remodeling is involved in the pathophysiology of AF, and it is tempting to speculate that VCAM-1 in circulation partly reflects local endocardial activation.…”

Loss of Multidrug Resistance–Associated Protein 1 Potentiates Chronic Doxorubicin-Induced Cardiac Dysfunction in Mice

“…The protein concentrations of heart ventricle homogenates were determined with the bicinchoninic acid protein assay. The measurement of GSH and GSSG by high-performance liquid chromatography was performed exactly as described (Deng et al, 2015) and used by others (Yamazaki et al, 2008(Yamazaki et al, , 2012Yamazaki and Villarreal, 2011;Kennedy et al, 2013;Barajas-Espinosa et al, 2014). The use of authentic GSH and GSSG to develop the standard curves ensured quantitation of the correct entities by high-performance liquid chromatography, thus validating the assay.…”

Elevated Glutathione Is Not Sufficient to Protect against Doxorubicin-Induced Nuclear Damage in Heart in Multidrug Resistance–Associated Protein 1 (Mrp1/Abcc1) Null Mice

“…The HPLC assay for GSH and GSSG is based on that developed by Senft et al (2000), and is used widely (Yamazaki et al, 2008(Yamazaki et al, , 2012Yamazaki and Villarreal, 2011;Kennedy et al, 2013;Barajas-Espinosa et al, 2014). Mouse heart homogenate was diluted with 0.5 volume of buffer A containing 15% metaphosphoric acid and mixed thoroughly, followed by centrifugation at 12,000 rpm for 15 minutes at 4°C.…”