Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.
Abstract | RATIONALE: Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A: cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. OBJECTIVE: The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. METHODS AND RESULTS: CONCLUSIONS: This study provided the first evidence that heregulin-beta(1) inhibits atherogenesis and suppresses macrophage foam cell formation via SR-A and ACAT1 downregulation and ABCA1 upregulation.
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Authors | Gang Xu, Takuya Watanabe, Yoshitaka Iso, Shinji Koba, Tetsuo Sakai, Masaharu Nagashima, Shigeko Arita, Shigeki Hongo, Hidekazu Ota, Youichi Kobayashi, Akira Miyazaki, Tsutomu Hirano |
Journal | Circulation research
(Circ Res)
Vol. 105
Issue 5
Pg. 500-10
(Aug 28 2009)
ISSN: 1524-4571 [Electronic] United States |
PMID | 19644050
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABCA1 protein, human
- APOA1 protein, human
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
- Antibodies
- Apolipoprotein A-I
- Apolipoproteins E
- Biomarkers
- CD36 Antigens
- Cholesterol Esters
- Lipoproteins, LDL
- Neuregulin-1
- RNA, Messenger
- SCARB1 protein, human
- Scavenger Receptors, Class A
- Scavenger Receptors, Class B
- acetyl-LDL
- heregulin alpha
- heregulin beta1
- ACAT1 protein, human
- Acetyl-CoA C-Acetyltransferase
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Topics |
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
(genetics, metabolism)
- Acetyl-CoA C-Acetyltransferase
(genetics, metabolism)
- Acute Coronary Syndrome
(blood, etiology)
- Adult
- Aged
- Aged, 80 and over
- Angina Pectoris
(blood, etiology)
- Animals
- Antibodies
(administration & dosage)
- Apolipoprotein A-I
(metabolism)
- Apolipoproteins E
(deficiency, genetics)
- Atherosclerosis
(blood, complications, prevention & control)
- Biological Transport
- Biomarkers
(blood)
- CD36 Antigens
(metabolism)
- Cells, Cultured
- Cholesterol Esters
(metabolism)
- Coronary Artery Disease
(blood, complications, prevention & control)
- Disease Models, Animal
- Down-Regulation
- Endocytosis
- Female
- Foam Cells
(metabolism)
- Humans
- Hypertension
(blood)
- Lipoproteins, LDL
(metabolism)
- Male
- Mice
- Mice, Knockout
- Middle Aged
- Neuregulin-1
(administration & dosage, blood, immunology, metabolism)
- RNA, Messenger
(metabolism)
- Rupture
- Scavenger Receptors, Class A
(genetics, metabolism)
- Scavenger Receptors, Class B
(metabolism)
- Severity of Illness Index
- Time Factors
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