title: Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome.
abstract: Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (P<0.02), near adventitia (P<0.003), and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (P<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.
authors.affiliation: Division of Cardiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Smoot
authors.forename: Nicole
authors.initials: N
authors.lastname: Wake
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.forename: Monica E
authors.initials: ME
authors.lastname: Kleinman
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: Armin
authors.initials: A
authors.lastname: Schwartzman
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000375:Aging / Q000502:physiology*; D055109:Ankle Brachial Index; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology*; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D006801:Humans; D008297:Male; D011371:Progeria / Q000453:epidemiology* / Q000503:physiopathology* / Q000628:therapy; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000502:physiology; D059289:Vascular Stiffness / Q000502:physiology
references.citation: J Am Coll Cardiol. 2008 Apr 1;51(13):1292-8
references.pmid: 18371562
references.citation: Hypertension. 2010 Feb;55(2):319-26
references.pmid: 20065154
references.citation: J Pediatr. 2005 Mar;146(3):336-41
references.pmid: 15756215
references.citation: Am J Med Genet A. 2006 Dec 1;140(23):2603-24
references.pmid: 16838330
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2154-9
references.pmid: 16461887
references.citation: Circulation. 2010 May 25;121(20):2200-10
references.pmid: 20458013
references.citation: J Am Soc Echocardiogr. 2006 Aug;19(8):943-54
references.pmid: 16880089
references.citation: N Engl J Med. 2008 Feb 7;358(6):592-604
references.pmid: 18256394
references.citation: Hypertension. 2009 Nov;54(5):919-50
references.pmid: 19729599
references.citation: Cardiovasc Pathol. 2001 May-Jun;10(3):133-6
references.pmid: 11485857
references.citation: Am J Hypertens. 2002 May;15(5):426-44
references.pmid: 12022246
references.citation: Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2301-9
references.pmid: 20798379
references.citation: J Neurol Sci. 2007 Jun 15;257(1-2):143-8
references.pmid: 17336336
references.citation: Nature. 2003 May 15;423(6937):293-8
references.pmid: 12714972
references.citation: Stroke. 2003 May;34(5):1203-6
references.pmid: 12677025
references.citation: Pediatrics. 2004 Aug;114(2 Suppl 4th Report):555-76
references.pmid: 15286277
references.citation: Clin Exp Hypertens. 2010 Jan;32(2):84-9
references.pmid: 20374190
references.citation: Pediatr Nephrol. 2008 Mar;23(3):439-44
references.pmid: 18097689
references.citation: Circ Res. 2007 Jul 6;101(1):13-26
references.pmid: 17615378
references.citation: Radiology. 2009 May;251(2):525-34
references.pmid: 19401577
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3250-5
references.pmid: 16492728
references.citation: Echocardiography. 2006 Feb;23(2):103-7
references.pmid: 16445726
references.citation: Circulation. 2002 Oct 15;106(16):2085-90
references.pmid: 12379578
references.citation: Hypertension. 2002 Jan;39(1):10-5
references.pmid: 11799071
references.citation: Science. 2006 May 19;312(5776):1059-63
references.pmid: 16645051
references.citation: J Am Med Dir Assoc. 2012 Mar;13(3):239-43
references.pmid: 21450208
references.citation: Hypertension. 2001 May;37(5):1236-41
references.pmid: 11358934
references.citation: J Clin Invest. 2011 Jul;121(7):2833-44
references.pmid: 21670498
references.citation: Science. 2003 Jun 27;300(5628):2055
references.pmid: 12702809
references.citation: Histochem Cell Biol. 1997 Jun;107(6):505-17
references.pmid: 9243284
references.citation: Atherosclerosis. 2007 Dec;195(2):411-4
references.pmid: 17462652