Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging.
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.
Olive
Michelle
M
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Harten
Ingrid
I
Mitchell
Richard
R
Beers
Jeanette K
JK
Djabali
Karima
K
Cao
Kan
K
Erdos
Michael R
MR
Blair
Cecilia
C
Funke
Birgit
B
Smoot
Leslie
L
Gerhard-Herman
Marie
M
Machan
Jason T
JT
Kutys
Robert
R
Virmani
Renu
R
Collins
Francis S
FS
Wight
Thomas N
TN
Nabel
Elizabeth G
EG
Gordon
Leslie B
LB
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*
D034904:Lamin Type A
Biochem Biophys Res Commun. 1999 Apr 2;257(1):163-7
10092527
Biochem Soc Trans. 2007 Nov;35(Pt 5):853-6
17956231
Nature. 2003 May 15;423(6937):293-8
12714972
Am J Med Genet A. 2006 Dec 1;140(23):2603-24
16838330
Nat Rev Immunol. 2006 Jul;6(7):508-19
16778830
Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L976-86
11943662
Arterioscler Thromb Vasc Biol. 2000 May;20(5):1262-75
10807742
N Engl J Med. 2008 Feb 7;358(6):592-604
18256394
Science. 2006 May 19;312(5776):1059-63
16645051
Am J Physiol Gastrointest Liver Physiol. 2010 Jan;298(1):G126-32
19910526
Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10271-10276
16801550
Science. 2003 Jun 27;300(5628):2055
12702809
J Pediatr. 2005 Mar;146(3):336-41
15756215
PLoS One. 2007 Dec 05;2(12):e1269
18060063
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8703-8
16738054
Physiol Rev. 2004 Jul;84(3):767-801
15269336
Am J Clin Pathol. 1970 Feb;53(2):243-53
5415913
J Cell Sci. 2006 Aug 15;119(Pt 16):3265-72
16899817
Mech Ageing Dev. 2010 Jan;131(1):2-8
19958786
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18111-6
15608054
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2154-9
16461887
Circulation. 2001 Feb 20;103(7):934-40
11181466
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3250-5
16492728
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4949-54
17360355
Circulation. 2010 May 25;121(20):2200-10
20458013
Cardiovasc Pathol. 2001 May-Jun;10(3):133-6
11485857
Am J Cardiol. 2003 Feb 6;91(3A):7A-11A
12645638
Am J Physiol Renal Physiol. 2004 Jan;286(1):F46-57
14519596
J Pathol. 2008 Mar;214(4):531
18264996
Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1259-68
17395854
J Med Genet. 2004 Apr;41(4):304-8
15060110
Aging Cell. 2008 Jun;7(3):383-93
18331619