Abstract 3914: Cardiac Mast Cell Stabilization Prevents the Progression of Cardiac Remodeling
Mast cells originate from bone marrow and migrate from the circulation into the cardiac tissue being mainly recruited by the locally produced chemokine, stem cell factor. Cardiac mast cell increases in the progression of heart failure (HF) and generates various substances not only chymase which is an ACE independent angiotensin-II formation enzyme but also tumor necrotic factor (TNF) -alpha and transforming growth factor (TGF)-beta. Mast cell stabilization may become one of the strategy in the treatment of inflammatory process in HF. Since statins seem to exert cardiac anti-inflammatory effects independent of the lipid lowering effect, we evaluated the long-term effects of pitavastatin (0.3mg/kg/day, 4weeks) on changes in cardiac function, the number of mast cells and the expression of several inflammatory related genes in dogs with tachycardia induced HF. Our results are shown in the Table⇓. In HF, the number of mast cells and the expression of stem cell factor increased in the left ventricle compared with the normals, however, the pitavastatin significantly decreased them. The agent significantly decreased LV filling pressure, shortened the tau and downregulated the expression of chymase, TNF-alpha and TGF-beta mRNA. The agent also decreased collagen deposits compared with the HF group. Cardiac mast cell stabilaization using a statin improved diastolic dysfunction, via modification of inflammatory substances as well as suppression of fibrosis in HF. It becomes an important strategy in the prevention of cardiac remodeling.