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Biomechanical Strain Induces Class A Scavenger Receptor Expression in Human Monocyte/Macrophages and THP-1 Cells: A Potential Mechanism of Increased Atherosclerosis in Hypertension

Background—Although hypertension is an important risk factor for the development of atherosclerosis, the mechanisms for this interaction are incompletely described. Previous studies have suggested that biomechanical strain regulates macrophage phenotype. We tested the hypothesis that biomechanical strain can induce expression of the class A scavenger receptor (SRA), an important lipoprotein receptor in atherogenesis. Methods and Results—Human monocyte/macrophages or THP-1 cells were cultured in a device that imposes uniform biaxial cyclic 1-Hz strains of 0%, 1%, 2%, or 3%, and SRA expression was analyzed. Mechanical strains induced SRA mRNA (3.5±0.6-fold at 3% strain for 48 hours, P <0.01) and SRA protein in THP-1 cells in an amplitude-dependent manner. This induction was accompanied by augmented expression of the class B scavenger receptor CD36 (2.8±0.3-fold, P <0.001) but not by increased peroxisome proliferator–activated receptor-&ggr; expression. To evaluate this effect in vivo, apolipoprotein E−/− mice were randomly assigned to receive standard chow, a high-cholesterol diet, or a high-cholesterol diet with hypertension induced by angiotensin II infusion for 8 weeks. Immunohistochemistry revealed that among macrophages in atherosclerotic lesions of the aorta, the proportion of macrophages with SRA expression was highest in hypertensive animals on a high-cholesterol diet (43.9±0.7%, versus 12.0±2.0% for normotensive animals on a high-cholesterol diet and 4.7±4.7% for animals on standard chow;P <0.001). Conclusions—Biomechanical strain induces SRA expression by monocyte/macrophages, suggesting a novel mechanism for promotion of atherosclerosis in hypertensive patients.