title: Role of miR-195 in aortic aneurysmal disease.
abstract: BACKGROUND
  Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix.
  
  
  OBJECTIVE
  Our aim was to assess the effect of the miR-15 family on aortic aneurysm development.
  
  
  RESULTS
  Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E-deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E-deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter.
  
  
  CONCLUSIONS
  We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.). anna.zampetaki@kcl.ac.uk manuel.mayr@kcl.ac.uk.
authors.forename: Anna
authors.initials: A
authors.lastname: Zampetaki
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Rizwan
authors.initials: R
authors.lastname: Attia
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Ursula
authors.initials: U
authors.lastname: Mayr
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Renata S M
authors.initials: RS
authors.lastname: Gomes
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Alkystis
authors.initials: A
authors.lastname: Phinikaridou
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Langley
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Ruifang
authors.initials: R
authors.lastname: Lu
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Bruce
authors.initials: B
authors.lastname: Fanshawe
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Marika
authors.initials: M
authors.lastname: Fava
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Javier
authors.initials: J
authors.lastname: Barallobre-Barreiro
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Chris
authors.initials: C
authors.lastname: Molenaar
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Po-Wah
authors.initials: PW
authors.lastname: So
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Abeera
authors.initials: A
authors.lastname: Abbas
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahangiri
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Waltham
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Rene
authors.initials: R
authors.lastname: Botnar
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
authors.affiliation: From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.). anna.zampetaki@kcl.ac.uk manuel.mayr@kcl.ac.uk.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D000368:Aged; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C552722:MIRN195 microRNA, human; D035683:MicroRNAs
keywords: aneurysm; biological markers; extracellular matrix; microRNAs; myocytes, smooth muscle