Confirmation of LOX-1 Deletion LOX-1 Deletion and Fibroblast Proliferation

Heart failure resulting from cardiac remodeling is the leading cause of morbidity and mortality in the United States and is becoming a major problem worldwide. The remodeling process is defined as progressive increase in ventricular wall volume and myocardial mass. The increase in cardiac mass comes from hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts, resulting in collagen secretion and resultant fibrosis. Cardiac fibroblasts constitute ≈25% of myocardial tissue volume and account for ≈60% of all cells in the heart. However, the cardiac cell makeup can vary in different species.– In any case, fibroblasts are an important component of the heart. The increased cardiac mass during remodeling process is largely because of inappropriate fibroblast proliferation. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a lectin-like 52-kDa receptor for oxidized low-density lipoprotein (LDL), is responsible for binding and uptake of ox-LDL, as well as other ligands exhibiting oxidized phospholipids, including injured and apoptotic cells. In recent studies, LOX-1 deletion was shown to limit cardiac hypertrophy and the remodeling process in mice subjected to sustained hypertension or myocardial ischemia.– Part of the decrease in cardiac remodeling with LOX-1 deletion seems to be related to reduction in fibrosis in the heart. In view of markedly reduced collagen deposition and fibrosis in the LOX-1 knockout (KO) mice hearts, we posited that LOX-1 may modulate fibroblast growth, a key factor for cardiac fibrosis. This study was designed to elucidate the role of LOX-1 on cardiac fibroblast growth and collagen secretion. Our study provides powerful evidence that LOX-1 is a major regulator of cardiac fibroblast growth, cytoskeleton, and function.