VIP Gene Deletion in Mice Causes Cardiomyopathy Associated with Upregulation of Heart Failure Genes

• DOI: 10.1371/journal.pone.0061449
• Publication Date: 2013-05-20T21:09:13Z
• Authors: Anthony M. Szema; Sayyed A. Hamidi; S. David Smith; Helene Benveniste
• Keywords: Dilated Cardiomyopathy

Rationale Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in arteries patients with idiopathic arterial hypertension (PAH). We previously determined that targeted deletion the VIP gene mice leads to PAH remodeling right ventricular (RV) dilatation. Whether left ventricle also affected by unknown. In current study, we examined if knockout (VIP−/−) develop both (LV) cardiomyopathy, manifested LV dilatation systolic dysfunction, as well overexpression genes conducive heart failure. Methods VIP−/−and wild type (WT) using Magnetic Resonance Imaging (MRI) for evidence cardiomyopathy associated biventricular dilation wall thickness changes. Lung tissue from VIP−/− WT was subjected whole-genome microarray analysis. Results Lungs showed genes: Myh1 upregulated 224 times over WT, Mylpf increased 72 fold. Tnnt3 105 tnnc2 181 Hearts were dilated mice, thinning increase RV chamber size, though enlargement varied. Weights consistently lower. Conclusions Critically-important failure-related are spontaneous phenotype, involving ventricles, suggesting loss orchestrates panoply pathogenic which detrimental cardiac homeostasis.