Lin YS, et al. - Researchers intended to ascertain the molecular mechanisms through which myocardial dysfunction is induced by high-demand pacing. For this purpose, they used dependent right ventricular septal pacing for 6 months to create atrioventricular block in pigs and assessed dyssynchrony between pacing (n=6) and sham control (n=6) groups by using echocardiography. Differentially expressed genes (DEGs) in the left ventricular (LV) myocardium of these two groups were identified using microarray and enrichment analyses. A significant increase in mechanical dyssynchrony resulting from pacing was evident. They noted inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway by 5 DEGs (ABCA1, APOD, CLU, LY96, and SERPINF1) in the LV septum (z-score=−0.447) and 5 DEGs (APOD, CLU, LY96, MSR1, and SERPINF1) in the LV free wall (z-score=−1.000); activation of the integrin-linked kinase (ILK) pathway in the LV septum (z-score=1.000) by 4 DEGs (ACTA2, MYL1, PPP2R3A, and SNAI2) was also reported. Overall, they concluded that, via inhibition of the LXR/RXR pathway, right ventricular septal-dependent pacing was related to persistent LV dyssynchrony–induced cardiomyopathy.