New anti–monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E–knockout mice
W Ni, K Egashira, S Kitamoto, C Kataoka, M Koyanagi… - Circulation, 2001 - Am Heart Assoc
W Ni, K Egashira, S Kitamoto, C Kataoka, M Koyanagi, S Inoue, K Imaizumi, C Akiyama…
Circulation, 2001•Am Heart AssocBackground—Monocyte recruitment into the arterial wall and its activation may be the
central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important
chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo
response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been
clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be
a unique site-specific gene therapy. Methods and Results—We devised a new strategy for …
central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important
chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo
response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been
clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be
a unique site-specific gene therapy. Methods and Results—We devised a new strategy for …
Background—Monocyte recruitment into the arterial wall and its activation may be the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be a unique site-specific gene therapy.
Methods and Results—We devised a new strategy for anti–MCP-1 gene therapy to treat atherosclerosis by transfecting an N-terminal deletion mutant of the human MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E–knockout mice. This strategy effectively blocked MCP-1 activity and inhibited the formation of atherosclerotic lesions but had no effect on serum lipid concentrations. Furthermore, this strategy increased the lesional extracellular matrix content.
Conclusions—We conclude that this anti–MCP-1 gene therapy may serve not only to reduce atherogenesis but also to stabilize vulnerable atheromatous plaques. This strategy may be a useful and feasible form of gene therapy against atherosclerosis in humans.
Am Heart Assoc
