title: Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions.
abstract: 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.
authors.affiliation: Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.|Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Bacteriology, Niigata University Graduate School of Medicine, Niigata, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.|Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Sakurai
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.|Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.|Department of Education, Shitennoji University, Habikino, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000804:Angiotensin II; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000097382:CD68 Molecule
chemical_list: D000804:Angiotensin II; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018799:Intercellular Adhesion Molecule-1; D017395:Plasminogen Activator Inhibitor 1; C067980:CD68 antigen, human; D000097382:CD68 Molecule