Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging.
Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging.
复制标题
DOI：
10.1161/atvbaha.110.209460
复制
发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Gordon LB
中科院分区：
文献类型：
--
作者：
Olive M;Harten I;Mitchell R;Beers JK;Djabali K;Cao K;Erdos MR;Blair C;Funke B;Smoot L;Gerhard-Herman M;Machan JT;Kutys R;Virmani R;Collins FS;Wight TN;Nabel EG;Gordon LB
患有哈钦森-吉尔福德早衰综合征（HGPS）的儿童在7岁至20岁之间表现出急剧加速的心血管疾病（CVD），导致心肌梗死或中风死亡。我们首次对遗传证实的HGPS和衰老的CVD进行了组织学比较评价。我们对两名死于心肌梗死的HGPS患儿的心血管组织进行了结构和免疫组织学分析。两者都具有与衰老引起的动脉粥样硬化以及小血管的小动脉硬化相关的典型特征。此外，血管表现出明显的外膜纤维化，这是先前未描述的HGPS特征。重要的是，尽管在HGPS患者冠状动脉中检测到的progerin的比例更高，但在非HGPS患者中也存在。在1个月至97岁之间，冠状动脉中progerin染色平均每年增加3.34% （P<0.0001）。我们发现心血管病理的许多方面之间的一致性在HGPS和老年患者。与典型CVD相比，HGPS可产生更显著的内皮纤维化。在年轻的非hgps个体中，血管早衰蛋白的生成在整个生命过程中显著增加，这强烈表明早衰蛋白在一般人群的心血管衰老中起作用。
Children with Hutchinson–Gilford progeria syndrome (HGPS) exhibit dramatically accelerated cardiovascular disease (CVD) causing death from myocardial infarction or stroke between ages 7 and 20 years. We undertook the first histological comparative evaluation between genetically confirmed HGPS and the CVD of aging. We present structural and immunohistological analysis of cardiovascular tissues from two 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. Additionally, vessels exhibited prominent adventitial fibrosis, a previously undescribed feature of HGPS. Importantly, though progerin was detected at higher rates in the HGPS coronary arteries, it was also present in non-HGPS individuals. Between ages one month and 97 years, progerin staining increased an average of 3.34% per year (P<0.0001) in coronary arteries. We find concordance between 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 the CV aging of the general population.