抄録
Hypertension is one of the most important cardiovascular risk factors and results in macrophage infiltration of blood vessels. However, how macrophages coordinate inflammatory responses with endothelial cells (ECs) remains unclear. In this study, we investigated whether exosomes upregulate the expression of inflammatory factors in ECs under hypertensive conditions. Hypertension was induced in rats by continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat serum by density gradient and ultracentrifugation and used to stimulate human coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and exosomes from human THP-1-derived macrophages were analyzed. Administration of Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts, suggesting enhanced infiltration of macrophages. In addition, the expression of intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1 (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts compared with control rats. CD68 protein expression and an increase in the expression of some exosome markers were detected in exosomes from hypertensive rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression, was markedly decreased in exosomes from hypertensive rat serum compared with exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced levels of miR-17 compared with exosomes from unstimulated cells. These results suggest that inflammation of ECs under hypertensive conditions is caused, at least in part, by macrophage-derived exosomes.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 353-360 |
| ページ数 | 8 |
| ジャーナル | Hypertension Research |
| 巻 | 40 |
| 発行部数 | 4 |
| DOI | |
| 出版物ステータス | Published - 2017 4 1 |
| 外部発表 | Yes |
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Keywords
ASJC Scopus subject areas
- Internal Medicine
- Physiology
- Cardiology and Cardiovascular Medicine
これを引用
Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions. / Osada-Oka, Mayuko; Shiota, Masayuki; Izumi, Yasukatsu; Nishiyama, Masaki; Tanaka, Masako; Yamaguchi, Takehiro; Sakurai, Emi; Miura, Katsuyuki; Iwao, Hiroshi.
：: Hypertension Research, 巻 40, 番号 4, 01.04.2017, p. 353-360.研究成果: Article
}
TY - JOUR
T1 - Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions
AU - Osada-Oka, Mayuko
AU - Shiota, Masayuki
AU - Izumi, Yasukatsu
AU - Nishiyama, Masaki
AU - Tanaka, Masako
AU - Yamaguchi, Takehiro
AU - Sakurai, Emi
AU - Miura, Katsuyuki
AU - Iwao, Hiroshi
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Hypertension is one of the most important cardiovascular risk factors and results in macrophage infiltration of blood vessels. However, how macrophages coordinate inflammatory responses with endothelial cells (ECs) remains unclear. In this study, we investigated whether exosomes upregulate the expression of inflammatory factors in ECs under hypertensive conditions. Hypertension was induced in rats by continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat serum by density gradient and ultracentrifugation and used to stimulate human coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and exosomes from human THP-1-derived macrophages were analyzed. Administration of Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts, suggesting enhanced infiltration of macrophages. In addition, the expression of intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1 (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts compared with control rats. CD68 protein expression and an increase in the expression of some exosome markers were detected in exosomes from hypertensive rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression, was markedly decreased in exosomes from hypertensive rat serum compared with exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced levels of miR-17 compared with exosomes from unstimulated cells. These results suggest that inflammation of ECs under hypertensive conditions is caused, at least in part, by macrophage-derived exosomes.
AB - Hypertension is one of the most important cardiovascular risk factors and results in macrophage infiltration of blood vessels. However, how macrophages coordinate inflammatory responses with endothelial cells (ECs) remains unclear. In this study, we investigated whether exosomes upregulate the expression of inflammatory factors in ECs under hypertensive conditions. Hypertension was induced in rats by continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat serum by density gradient and ultracentrifugation and used to stimulate human coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and exosomes from human THP-1-derived macrophages were analyzed. Administration of Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts, suggesting enhanced infiltration of macrophages. In addition, the expression of intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1 (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts compared with control rats. CD68 protein expression and an increase in the expression of some exosome markers were detected in exosomes from hypertensive rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression, was markedly decreased in exosomes from hypertensive rat serum compared with exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced levels of miR-17 compared with exosomes from unstimulated cells. These results suggest that inflammation of ECs under hypertensive conditions is caused, at least in part, by macrophage-derived exosomes.
KW - Angiotensin II
KW - endothelial cells
KW - endothelial cells
KW - exosomes
KW - exosomes
KW - inflammation
KW - inflammation
KW - macrophages
KW - macrophagesangiotensin II
UR - http://www.scopus.com/inward/record.url?scp=85017127527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017127527&partnerID=8YFLogxK
U2 - 10.1038/hr.2016.163
DO - 10.1038/hr.2016.163
M3 - Article
VL - 40
SP - 353
EP - 360
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 4
ER -