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.


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-gamma 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.
Sakamoto
H
H
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aikawa
M
M
Hill
C C
CC
Weiss
D
D
Taylor
W R
WR
Libby
P
P
Lee
R T
RT
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013314:Stress, Mechanical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis
D057911:Angiotensin Receptor Antagonists; D001057:Apolipoproteins E; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D008565:Membrane Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014157:Transcription Factors; D000804:Angiotensin II; D019808:Losartan; D013755:Tetradecanoylphorbol Acetate