Pro-fibrotic effect of oxidized LDL in cardiac myofibroblasts

Abstract

Inflammatory signals associated with cardiac diseases trigger trans-differentiation of cardiac fibroblasts to cardiac myofibroblasts. Cardiac myofibroblasts are the main cell type involved in the development of cardiac fibrosis, a diffuse and disproportionate accumulation of collagen in the myocardium. Although the role of the scavenger like-lectin receptor LOX-1 was previously investigated in cardiac fibroblasts and fibrosis, the involvement of the LOX-1 ligand -oxidized low-density lipoprotein (oxLDL)- on cardiac myofibroblast function still remains unexplored. In the present work, we investigated the effect of oxLDL/LOX-1 on fibrotic markers and cardiac myofibroblast function. Our in vitro results showed that oxLDL increased cardiac myofibroblast proliferation, triggered an increase in the synthesis of collagen type I and fibronectin containing extra domain A, and stimulated collagen type I secretion. oxLDL also decreased cardiac myofibroblast migration, collagen gel contraction and cell area, without modifying α-smooth muscle actin protein levels. These effects were dependent on LOX-1, because LOX-1 knockdown abolished oxLDL effects. Collectively these data showed that oxLDL has important modulatory effects on cardiac myofibroblast function.

Keywords: Cardiac myofibroblast; Cholesterol; Fibrosis; Heart; LOX-1; Oxidized LDL.