Monocyte chemoattractant protein-1 is upregulated in rats with volume-overload congestive heart failure.
BACKGROUND
Chemokines are potent proinflammatory and immune modulators. Increased expression of chemokines, eg, monocyte chemoattractant protein-1 (MCP-1), has recently been described in clinical and experimental heart failure. The present report is aimed at exploring the expression, localization, and 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).


RESULTS
An aortocaval fistula was surgically created between the abdominal aorta and inferior vena cava. Rats with CHF were further subdivided into compensated and decompensated subgroups. Northern blot analysis and real-time quantitative polymerase chain reaction demonstrated upregulation of MCP-1 mRNA expression correlating with the severity of CHF (288+/-22, 502+/-62, and 826+/-138 copies/ng total RNA for sham, compensated, and 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 fibroblasts, and its intensity increased with severity of CHF. In addition, rats with CHF displayed a significant decrease of (125)I-labeled MCP-1 binding sites 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 the expression, immunohistochemical localization, and receptor binding of the 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 development of CHF in rats with aortocaval fistula.
Behr
T M
TM
Cardiovascular Pharmacology, SmithKline Beecham, King of Prussia, PA 19406, USA. thomas_m_behr@sbphrd.com
Wang
X
X
Aiyar
N
N
Coatney
R W
RW
Li
X
X
Koster
P
P
Angermann
C E
CE
Ohlstein
E
E
Feuerstein
G Z
GZ
Winaver
J
J
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D018932:Chemokine CCL2 / Q000378:metabolism*; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014463:Ultrasonography; D015854:Up-Regulation
D018932:Chemokine CCL2; D012333:RNA, Messenger