Cardiovascular Pathology in Hutchinson-Gilford Progeria: Correlation With the Vascular Pathology of Aging

被引：309

作者：

Olive, Michelle ^{[2
]}

Harten, Ingrid ^{[3
,4
]}

Mitchell, Richard ^{[5
]}

Beers, Jeanette K. ^{[2
]}

Djabali, Karima ^{[7
]}

Cao, Kan ^{[9
]}

Erdos, Michael R. ^{[9
]}

Blair, Cecilia ^{[9
]}

Funke, Birgit ^{[8
,10
]}

Smoot, Leslie ^{[11
]}

Gerhard-Herman, Marie ^{[6
]}

Machan, Jason T. ^{[13
,14
]}

Kutys, Robert ^{[15
]}

Virmani, Renu ^{[15
]}

Collins, Francis S. ^{[9
]}

Wight, Thomas N. ^{[3
,4
]}

Nabel, Elizabeth G. ^{[2
]}

Gordon, Leslie B. ^{[1
,12
]}

机构：

[1] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA

[2] NHLBI, NIH, Bethesda, MD 20892 USA

[3] Benaroya Res Inst Virginia Mason, Hope Heart Program, Seattle, WA USA

[4] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA

[7] Univ Technol Munich, Dept Dermatol, Munich, Germany

[8] Mol Med Lab, Cambridge, MA USA

[9] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA

[10] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[11] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA

[12] Childrens Hosp Boston, Dept Anesthesia, Boston, MA USA

[13] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Orthopaed, Providence, RI 02912 USA

[14] Brown Univ, Warren Alpert Med Sch, Dept Surg, Providence, RI 02912 USA

[15] CVPath Inst Inc, Gaithersburg, MD USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2010年 / 30卷 / 11期

基金：

美国国家卫生研究院;

关键词：

aging; atherosclerosis; pathology; peripheral arterial disease; progeria; SUDDEN CORONARY DEATH; ATHEROSCLEROSIS; CELLS; INHIBITORS; MUTATIONS; PHENOTYPE; FIBROSIS; ARTERIES; ANTIBODY; DEFECTS;

D O I：

10.1161/ATVBAHA.110.209460

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. Methods and 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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2010;30:2301-2309.)

引用

页码：2301 / U636

页数：26

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