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Published on: October 17, 2017
Role of mechanical stress in monocytes/macrophages: implications for atherosclerosis
Keiji Yamamoto1, Uichi Ikeda, Kazuyuki Shimada
1Division of Cardiovascular Medicine, Jichi Medical School, Minamikawachi-Machi, Tochigi 329-0498, Japan. kyamamoto@jichi.ac.jp
Insights
Mechanical stress from hypertension deforms monocytes/macrophages, increasing matrix metalloproteinases and scavenger receptors. This contributes to atherosclerosis progression and plaque instability.
Area of Science:
- Cardiovascular Biology
- Cellular Biomechanics
- Atherosclerosis Research
Background:
- Hypertension is a known risk factor for atherosclerosis, but underlying molecular mechanisms are unclear.
- Vascular cells, including monocytes and macrophages, interact with mechanical forces, influencing cardiovascular disease.
- Macrophages are implicated in atherogenesis and plaque rupture, yet the impact of mechanical stress on their function is not fully understood.
Purpose of the Study:
- To investigate the effects of biomechanical forces on monocyte/macrophage function.
- To elucidate the molecular mechanisms linking hypertension-induced mechanical stress to atherosclerosis.
- To determine how mechanical deformation influences macrophage behavior in the context of atherogenesis.
Main Methods:
- Exposing human monocytes/macrophages and THP-1 cells to biomechanical strain.
- Analyzing gene expression changes using DNA microarrays.
- Assessing the induction of matrix metalloproteinases and immediate-early genes.
Main Results:
- Biomechanical deformation selectively augmented matrix metalloproteinases and induced immediate-early genes in monocytes/macrophages.
- Cyclic mechanical strain induced the expression of the class A scavenger receptor in these cells.
- Specific genes like interleukin-8 and IEX-1 were upregulated by cyclic mechanical strain in THP-1 cells.
Conclusions:
- Biomechanical deformation of monocytes/macrophages contributes to extracellular matrix degradation and monocyte differentiation.
- Mechanical stress, such as that from hypertension, plays a significant role in promoting atherosclerosis.
- These findings highlight the role of mechanical forces in atherogenesis and coronary artery plaque instability via vascular macrophages.
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 immediate-early 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.
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