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John Fallon

  • ADJUNCT PROFESSOR Medicine, Cardiology
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  • Anatomic Pathology


  • MD/PHD, Albany Medical College

  • Residency, Pathology
    Massachusetts General Hospital

  • Fellowship, Pathology
    Massachusetts General Hospital



Fayad ZA, Fallon JT, Shinnar M, Wehrli S, Dansky HM, Poon M, Badimon JJ, Charlton SA, Fisher EA, Breslow JL, Fuster V. Noninvasive In vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice. Circulation 1998; 98: 1541-1547.

Haque N, Zhang X, French D, Li J, Poon M, Fallon J, Gabel BR, Taubman M, Harpel P. CC chemokine I-309 is the principal monocyte chemoattractant induced by apolipoprotein(a) in human vascular endothelial cells. Circulation 2000 Aug 15; 102(7): 786-92.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis; however, the mechanisms are unclear. We previously reported that Lp(a) stimulated human vascular endothelial cells to produce monocyte chemotactic activity. The apolipoprotein(a) [apo(a)] portion of Lp(a) was the active moiety. METHODS AND RESULTS: We now describe the identification of the chemotactic activity as being due to the CC chemokine I-309. The carboxy-terminal domain of apo(a) containing 6 type-4 kringles (types 5 to 10), kringle V, and the protease domain was demonstrated to contain the I-309-inducing portion. Polyclonal and monoclonal anti-I-309 antibodies as well as an antibody against a portion of the extracellular domain of CCR8, the I-309 receptor, inhibited the increase in monocyte chemotactic activity induced by apo(a). I-309 antisense oligonucleotides also inhibited the induction of endothelial monocyte chemotactic activity by apo(a). I-309 mRNA was identified in human umbilical vein endothelial cells. Apo(a) induced an increase in I-309 protein in the endothelial cytoplasm and in the conditioned medium. Immunohistochemical studies have identified I-309 in endothelium, macrophages, and extracellular areas of human atherosclerotic plaques and have found that I-309 colocalized with apo(a). CONCLUSIONS: These data establish that I-309 is responsible for the monocyte chemotactic activity induced in human umbilical vein endothelial cells by Lp(a). The identification of the endothelial cell as a source for I-309 suggests that this chemokine may participate in vessel wall biology. Our data also suggest that I-309 may play a role in mediating the effects of Lp(a) in atherosclerosis.

Industry Relationships

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Dr.Fallon is not currently required to report Industry relationships.

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