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COMMENTARIES
POSTED IN AUGUST 2009
γ-Secretase
Inhibitors as Antiatherosclerotic Therapy
Authors: Kyosuke Takeshita,
Toru Aoyama, Ryosuke Kikuchi, Yasuhiro Uchida, Koji Yamamoto,
Hideo Nakamura, and Toyoaki Murohara
Macrophages exacerbate inflammatory responses
of atheromatous plaques and structural instability [1].
Inflammatory plaque could therefore be a critical target
in atheromatous lesions to prevent atherogenesis [2,3].
In multiple organisms, the Notch signal pathway participates
in diverse processes, including cell-fate decisions in
the developmental stage, and tissue renewal and repair
in adults [4]. Notch signaling plays an especially critical
role in the development and pathophysiology of the cardiovascular
system. We previously reported that endothelial Notch1
plays a critical role in vasculogenesis during the developmental
process [5] and angiogenesis in the adult ischemic tissues
[6]. Further we also demonstrated that Notch1 mediates
proliferation of smooth muscle cells and neointimal formation
followed by vascular injury through CHF1/Hey2 [7].
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Heterogeneity
of Macrophages in Atherogenesis - Implications for
Therapy
Authors: Heather
M. Wilson
The concept that atherosclerosis is a chronic
inflammatory disease is now well recognized in the field
of cardiovascular research [1]. Leukocyte subsets from
both the innate and acquired immune system accumulate
in atherosclerotic lesions where they have been strongly
implicated in the pathogenesis. Macrophages were the
first inflammatory cells to be associated with the atherosclerosis
[2] and accumulation of cholesterol-loaded macrophages
in the arterial wall is the hallmark of the early atherosclerotic
lesion. Activated macrophages play a central role in
the atherogenic process not only as modulators of lipid
metabolism but through secretion of pro-inflammatory
cytokines, chemokines, and cytotoxic effector molecules.
However macrophages are heterogeneous cells and are also
involved in tissue repair and healing. Targeting macrophage
activities therefore provides a novel approach for prevention
and treatment of atherosclerosis and other macrophage-mediated
diseases.
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