Biomechanical strain induces class a scavenger receptor expression in human monocyte/macrophages and THP-1 cells - A potential mechanism of increasedatherosclerosis in hypertension

Citation
H. Sakamoto et al., Biomechanical strain induces class a scavenger receptor expression in human monocyte/macrophages and THP-1 cells - A potential mechanism of increasedatherosclerosis in hypertension, CIRCULATION, 104(1), 2001, pp. 109-114
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
104
Issue
1
Year of publication
2001
Pages
109 - 114
Database
ISI
SICI code
0009-7322(20010703)104:1<109:BSICAS>2.0.ZU;2-H
Abstract
Background-Although hypertension is an important risk factor for the develo pment of atherosclerosis, the mechanisms for this interaction are incomplet ely described. Previous studies have suggested that biomechanical strain re gulates macrophage phenotype. We tested the hypothesis that biomechanical s train can induce expression of the class A scavenger receptor (SRA), an imp ortant lipoprotein receptor in atherogenesis. Methods and Results-Human monocyte/macrophages or THP-I 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 mR NA (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 accompanie d 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 re ceptor-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 macrophag es in atherosclerotic lesions of the aorta, the proportion of macrophages w ith SRA expression was highest in hypertensive animals on a high-cholestero l diet (43.9 +/-0.7%, versus 12.0 +/-2.0% for normotensive animals on a hig h-cholesterol diet and 4.7 +/-4.7% for animals on standard chow; P <0.001). Conclusions-Biomechanical strain induces SRA expression by monocyte/macroph ages, suggesting a novel mechanism for promotion of atherosclerosis in hype rtensive patients.