title: Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging.
abstract: OBJECTIVE
  Children with Hutchinson-Gilford progeria syndrome (HGPS) exhibit dramatically accelerated cardiovascular disease (CVD), causing death from myocardial infarction or stroke between the ages of 7 and 20 years. We undertook the first histological comparative evaluation between genetically confirmed HGPS and the CVD of aging.
  
  
  RESULTS
  We present structural and immunohistological analysis of cardiovascular tissues from 2 children with HGPS who died of myocardial infarction. Both had features classically associated with the atherosclerosis of aging, as well as arteriolosclerosis of small vessels. In addition, vessels exhibited prominent adventitial fibrosis, a previously undescribed feature of HGPS. Importantly, although progerin was detected at higher rates in the HGPS coronary arteries, it was also present in non-HGPS individuals. Between the ages of 1 month and 97 years, progerin staining increased an average of 3.34% per year (P<0.0001) in coronary arteries.
  
  
  CONCLUSIONS
  We find concordance among many aspects of cardiovascular pathology in both HGPS and geriatric patients. HGPS generates a more prominent adventitial fibrosis than typical CVD. Vascular progerin generation in young non-HGPS individuals, which significantly increases throughout life, strongly suggests that progerin has a role in cardiovascular aging of the general population.
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Olive
authors.forename: Ingrid
authors.initials: I
authors.lastname: Harten
authors.forename: Richard
authors.initials: R
authors.lastname: Mitchell
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Beers
authors.forename: Karima
authors.initials: K
authors.lastname: Djabali
authors.forename: Kan
authors.initials: K
authors.lastname: Cao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Cecilia
authors.initials: C
authors.lastname: Blair
authors.forename: Birgit
authors.initials: B
authors.lastname: Funke
authors.forename: Leslie
authors.initials: L
authors.lastname: Smoot
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.forename: Jason T
authors.initials: JT
authors.lastname: Machan
authors.forename: Robert
authors.initials: R
authors.lastname: Kutys
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Nabel
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000375:Aging / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000473:pathology; D002648:Child; D003324:Coronary Artery Disease / Q000473:pathology*; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000032:analysis; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D011371:Progeria / Q000150:complications / Q000473:pathology*
chemical_list: D034904:Lamin Type A
references.citation: Biochem Biophys Res Commun. 1999 Apr 2;257(1):163-7
references.pmid: 10092527
references.citation: Biochem Soc Trans. 2007 Nov;35(Pt 5):853-6
references.pmid: 17956231
references.citation: Nature. 2003 May 15;423(6937):293-8
references.pmid: 12714972
references.citation: Am J Med Genet A. 2006 Dec 1;140(23):2603-24
references.pmid: 16838330
references.citation: Nat Rev Immunol. 2006 Jul;6(7):508-19
references.pmid: 16778830
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L976-86
references.pmid: 11943662
references.citation: Arterioscler Thromb Vasc Biol. 2000 May;20(5):1262-75
references.pmid: 10807742
references.citation: N Engl J Med. 2008 Feb 7;358(6):592-604
references.pmid: 18256394
references.citation: Science. 2006 May 19;312(5776):1059-63
references.pmid: 16645051
references.citation: Am J Physiol Gastrointest Liver Physiol. 2010 Jan;298(1):G126-32
references.pmid: 19910526
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10271-10276
references.pmid: 16801550
references.citation: Science. 2003 Jun 27;300(5628):2055
references.pmid: 12702809
references.citation: J Pediatr. 2005 Mar;146(3):336-41
references.pmid: 15756215
references.citation: PLoS One. 2007 Dec 05;2(12):e1269
references.pmid: 18060063
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8703-8
references.pmid: 16738054
references.citation: Physiol Rev. 2004 Jul;84(3):767-801
references.pmid: 15269336
references.citation: Am J Clin Pathol. 1970 Feb;53(2):243-53
references.pmid: 5415913
references.citation: J Cell Sci. 2006 Aug 15;119(Pt 16):3265-72
references.pmid: 16899817
references.citation: Mech Ageing Dev. 2010 Jan;131(1):2-8
references.pmid: 19958786
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18111-6
references.pmid: 15608054
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2154-9
references.pmid: 16461887
references.citation: Circulation. 2001 Feb 20;103(7):934-40
references.pmid: 11181466
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3250-5
references.pmid: 16492728
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4949-54
references.pmid: 17360355
references.citation: Circulation. 2010 May 25;121(20):2200-10
references.pmid: 20458013
references.citation: Cardiovasc Pathol. 2001 May-Jun;10(3):133-6
references.pmid: 11485857
references.citation: Am J Cardiol. 2003 Feb 6;91(3A):7A-11A
references.pmid: 12645638
references.citation: Am J Physiol Renal Physiol. 2004 Jan;286(1):F46-57
references.pmid: 14519596
references.citation: J Pathol. 2008 Mar;214(4):531
references.pmid: 18264996
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1259-68
references.pmid: 17395854
references.citation: J Med Genet. 2004 Apr;41(4):304-8
references.pmid: 15060110
references.citation: Aging Cell. 2008 Jun;7(3):383-93
references.pmid: 18331619