Role of Mechanical Stress in Monocytes / Macrophages: Implications for Atherosclerosis

Author(s): Keiji Yamamoto, Uichi Ikeda, Kazuyuki Shimada.

Journal Name: Current Vascular Pharmacology

Volume 1 , Issue 3 , 2003

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Abstract:

Hypertension is a well-known risk factor for atherosclerosis, but the molecular mechanisms that link elevated blood pressure to atherosclerosis progression remain uncertain. The interactions of mechanical forces and cells of the vasculature are relevant to many cardiovascular diseases. Once a monocyte infiltrates a tissue, it establishes extracellular matrix contacts and is subjected to deformation through those contacts. Macrophages participate in atherogenesis and commonly localize at sites of coronary plaque rupture. Although macrophages may be subjected to excess mechanical stress in these conditions, how biomechanical forces affect macrophage function remains incompletely defined. Recent work demonstrates that human monocytes / macrophages respond to mechanical deformation with selective augmentation of matrix metalloproteinases and induction of immediateearly genes. In human monocytes / macrophages and THP-1 cells, biomechanical strain can induce expression of the class A scavenger receptor, an important lipoprotein receptor in atherogenesis. In addition, DNA microarray analysis reveals that cyclic mechanical strain induces only a few genes ( > 2.5-fold), including interleukin-8 and IEX- 1 in THP-1 cells. Thus, biomechanical deformation of monocytes / macrophages contributes to degradation of extracellular matrix, monocyte differentiation, and promotion of atherosclerosis. These findings suggest that mechanical stress in vivo, such as hypertension, may play an important role in atherogenesis and instability of coronary-artery plaques through biomechanical effects on vascular macrophages.

Keywords: Monocytes, hypertension, atherosclerosis, metalloproteinases, interleukin

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Article Details

VOLUME: 1
ISSUE: 3
Year: 2003
Page: [315 - 319]
Pages: 5
DOI: 10.2174/1570161033476565
Price: $58

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