doi: 10.1161/hc2701.091070
(Circulation. 2001;104:109.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Biomechanical Strain Induces Class A Scavenger Receptor Expression in Human Monocyte/Macrophages and THP-1 Cells
A Potential Mechanism of Increased Atherosclerosis in Hypertension
From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (H.S., M.A., C.C.H., P.L., R.T.L.); and the Division of Cardiology, Department of Medicine, Atlanta VA Medical Center and Emory University School of Medicine, Atlanta, Ga (D.W., W.R.T.).
Correspondence to Richard T. Lee, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail rlee{at}rics.bwh.harvard.edu
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-
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.
Key Words: strain • receptors • cells • atherosclerosis • hypertension
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