Monocyte chemoattractant protein-1 is upregulated in rats with volume-overload congestive heart failure

Background-Chemokines are potent proinflammatory and immune modulators. Inc reased expression of chemokines, eg, monocyte chemoattractant protein-1 (MC P-1), has recently been described in clinical and experimental heart failur e. The present report is aimed at exploring the expression, localization, a nd binding site regulation of MCP-1, a member of the C-C chemokine family, in a rat model of volume-overload congestive heart failure (CHF). Methods and Results-An aortocaval fistula was surgically created between th e abdominal aorta and inferior vena cava. Rats with CHF were further subdiv ided into compensated and decompensated subgroups. Northern blot analysis a nd real-rime quantitative polymerase chain reaction demonstrated upregulati on of MCP-1 mRNA expression correlating with the severity of CHF (288 +/- 2 2, 502 +/- 62, and 826 +/- 138 copies/ng total RNA for sham, compensated, a nd decompensated animals, respectively; n = 5, P < 0.05). MCP-1 protein was localized by immunohistochemistry in cardiomyocytes, vascular endothelium and smooth muscle cells, infiltrating leukocytes, and interstitial fibrobla sts, and its intensity increased with severity of CHF. In addition, rats wi th CHF displayed a significant decrease of I-125-labeled MCP-I binding site s to myocardium-derived membranes (384.3 +/- 57.0, 181.3 +/- 8.8, and 123.3 +/- 14.1 fmol/mg protein for sham, compensated, and decompensated animals, respectively). Conclusions-Volume-overload CHF in rats is associated with alterations in t he expression, immunohistochemical localization, and receptor binding of th e MCP-1 chemokine in the myocardium. These changes were more pronounced in rats with decompensated CHF. The data suggest that activation of the MCP-1 system may contribute to the progressive cardiac decompensation and develop ment of CHF in rats with aortocaval fistula.