LOX-1 in the maintenance of cytoskeleton and proliferation in senescent cardiac fibroblasts

Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is one of the most important receptors for binding and uptake of ox-LDL in endothelial cells, vascular smooth muscle cells and cardiomyocytes. In this study in cultured mice heart fibroblasts, we describe a decrease in LOX-1 expression as these cells go through successive passages. Further, fibroblast aging is associated with significant changes in morphology and proliferation ability. The same phenomena were observed in primary cardiac fibroblasts isolated from the aged mice (130-week). We also noted that the senescent fibroblasts have increased susceptibility to apoptosis and have a disorganized cytoskeleton. To ascertain the contribution of LOX-1 in the decline in proliferative ability and morphological changes in the aged cells, senescent fibroblasts were transfected with h-LOX-1. Transfection with h-LOX-1 resulted in cytoskeleton reorganization and partial restoration of the expression of related proteins, CDC42 and p70 S6 kinase. Upregulation of LOX-1 also significantly enhanced their proliferation potential and restored the expression of related genes Mdm2 and phos-Akt, and modestly reduced the expression of aging markers 4-HNE and β-catenin. These findings suggest that LOX-1 contributes, at least in part, to the process of fibroblast senescence and may be viewed as a new aging maker.