MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) GENE-EXPRESSION IN DILATEDCARDIOMYOPATHY

The cytotoxic action of leukocytes may be a most probable cause of car diac myocyte damage seen in chronic myocarditis and dilated cardiomyop athy (DCM), The migration and tissue infiltration of leukocytes is reg ulated by chemotactic cytokines, Recently, the presence of monocyte ch emoattractant protein 1 (MCP-1) messenger RNA has been demonstrated in endomyocardial biopsy tissue obtained from patients with CM, This che mokine could contribute to enhanced leukocyte recruitment and activati on resulting in chronic damage of cardiomyocytes, Accordingly, we soug ht to determine whether the severity of left ventricular dysfunction i n DCM is associated with quantitative alterations of MCP-1 messenger R NA and MCP-1 protein in endomyocardial biopsy tissue. A group of DCM p atients with low to moderate impairment of left ventricular function ( ejection fraction 45.3 +/- 2.3%, n = 7) was compared to patients with severe left ventricular dysfunction (ejection fraction 25.5 +/- 3.1%, it = 7), MCP-1 messenger RNA expression was determined by quantitative polymerase chain reaction. MCP-1 protein and the presence of infiltra ting inflammatory cells were detected by immunohistochemistry, DCM pat ients with severe left ventricular dysfunction showed a 2.35 fold high er MCP-1 messenger RNA expression when compared to DCM patients with l ess severe dysfunction (P = 0.0229), Positive immunohistochemical stai ning for MCP-1 was found in all seven patients with severe left ventri cular dysfunction and was particularly distinct within the cardiac int erstitium, In five of seven patients with less severe systolic dysfunc tion, MCP-1 protein was found, but was less pronounced and distributed in patchy interstitial areas, close to intramyocardial vessels, Furth ermore, there was a consistent trend toward a higher infiltration of i nflammatory cells in DCM patients with lower ejection fraction. In con clusion, MCP-1 is dynamically regulated in DCM related deterioration o f left ventricular function. This mechanism might contribute to myocyt e damage via infiltrated and activated monocytes, (C) 1998 Academic Pr ess.