Regulation of Lipoma Preferred Partner in the heart

Abstract

Adaptor proteins play an important role in signalling pathways by providing a platform on which many proteins interact. Malfunction or mislocalisation of these proteins play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work show that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic banded rats (p<0.05 n=4), but not after myocardial infarction, suggesting mechanical regulation of its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (P<0.05 n=3). LPP expression was down‐regulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48h (1Hz, 5% maximum strain), which decreased total LPP expression by 35% and membrane localization in subcellular fractions (P<0.05, n=5). LNAME, an inhibitor of NO synthase upregulated LPP expression but not smooth muscle actin. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by mechanical stress.