title: Angiotensin II increases expression and secretion of cathepsin F in cultured human monocyte-derived macrophages: an angiotensin II type 2 receptor-mediated effect.
abstract: Increasing evidence suggests that cathepsins and angiotensin II (AngII) participate in atherosclerosis, particularly in remodeling of the extracellular matrix of the inflamed arterial intima. Here, we show that AngII induces mRNA expression of cathepsin F, a member of the cysteine protease family, in human monocyte-derived macrophages. AngII did not affect the amount of intracellular cathepsin F protein, but significantly enhanced its secretion by the treated cells. The stimulatory effect of AngII was mediated by the AngII type 2 (AT(2)) receptor, as demonstrated by the ability of the AT(2)-receptor antagonist PD123319 to block the AngII-induced increase in cathepsin F secretion. Our present data demonstrate a novel proatherogenic role for AngII, namely its ability to enhance secretion of lysosomal cathepsin F by monocyte-derived macrophages.
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, Helsinki, Finland.
authors.forename: Riia
authors.initials: R
authors.lastname: Kaakinen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Mia
authors.initials: M
authors.lastname: Sneck
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Katariina
authors.initials: K
authors.lastname: Oörni
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D050197:Atherosclerosis / Q000209:etiology; D056646:Cathepsin F; D002403:Cathepsins / Q000096:biosynthesis* / Q000378:metabolism*; D002470:Cell Survival; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D002403:Cathepsins; C534090:CTSF protein, human; D056646:Cathepsin F; D019808:Losartan