title: Renin-sensitive microRNAs correlate with atherosclerosis plaque progression.
abstract: Recent trials with inhibition of the renin-angiotensin-aldosterone system (RAAS) in patients with established atherosclerosis have been equivocal. MicroRNAs (miRs) are known to affect multiple pathways relevant to atherosclerosis, including RAAS. We postulated that the use of a direct renin antagonist would result in differential regulation of miRs. We examined monocyte miR expression before and after treatment with renin antagonist, Aliskiren, in patients with established cardiovascular disease as part of a prospective, single-center, randomized, double-blind and placebo-controlled clinical trial (NCT01417104). After screening, patients (mean age 62±3 years) were randomized to placebo or Aliskiren. Three-dimensional dark-blood magnetic resonance imaging assessment of atherosclerosis in the thoracic and abdominal aorta was conducted at baseline and at study completion (19-36 weeks). MiR expression arrays were performed on RNA from peripheral blood mononuclear cells collected at baseline and 12 weeks following randomization to placebo or Aliskiren and showed that hsa-miR-106b-5p, 27a-3p and 18b-5p were significantly downregulated with Aliskiren. Baseline expression of these miRs positively correlated with normalized total wall volume in subjects taking Aliskiren (miR-106b, R=0.62; miR-27a, R=0.63; miR-18b, R=0.77; P<0.05). Hsa-miR-106b-5p, 27a-3p and 18b-5p may represent pathway-specific adaptations to renin inhibition relevant to atherosclerosis.
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Deiuliis
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: G
authors.initials: G
authors.lastname: Mihai
authors.affiliation: Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: C
authors.initials: C
authors.lastname: Taslim
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Varghese
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Maiseyeu
authors.affiliation: Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000503:physiopathology*; D011446:Prospective Studies; D012083:Renin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D035683:MicroRNAs; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren