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. 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.
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. 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: Dale K Shumaker; Thomas Dechat; Alexander Kohlmaier; Stephen A Adam; Matthew R Bozovsky; Michael R Erdos; Maria Eriksson; Anne E Goldman; Satya Khuon; Francis S Collins; Thomas Jenuwein; Robert D Goldman Journal: Proc Natl Acad Sci U S A Date: 2006-05-31 Impact factor: 11.205
Authors: Kan Cao; Brian C Capell; Michael R Erdos; Karima Djabali; Francis S Collins Journal: Proc Natl Acad Sci U S A Date: 2007-03-14 Impact factor: 11.205
Authors: Melissa A Merideth; Leslie B Gordon; Sarah Clauss; Vandana Sachdev; Ann C M Smith; Monique B Perry; Carmen C Brewer; Christopher Zalewski; H Jeffrey Kim; Beth Solomon; Brian P Brooks; Lynn H Gerber; Maria L Turner; Demetrio L Domingo; Thomas C Hart; Jennifer Graf; James C Reynolds; Andrea Gropman; Jack A Yanovski; Marie Gerhard-Herman; Francis S Collins; Elizabeth G Nabel; Richard O Cannon; William A Gahl; Wendy J Introne Journal: N Engl J Med Date: 2008-02-07 Impact factor: 91.245
Authors: Dayle McClintock; Desiree Ratner; Meepa Lokuge; David M Owens; Leslie B Gordon; Francis S Collins; Karima Djabali Journal: PLoS One Date: 2007-12-05 Impact factor: 3.240
Authors: Mark W Majesky; Xiu Rong Dong; Virginia Hoglund; Gunter Daum; William M Mahoney Journal: Cells Tissues Organs Date: 2011-10-14 Impact factor: 2.481
Authors: Fuki M Hisama; Davor Lessel; Dru Leistritz; Katrin Friedrich; Kim L McBride; Matthew T Pastore; Gary S Gottesman; Bidisha Saha; George M Martin; Christian Kubisch; Junko Oshima Journal: Am J Med Genet A Date: 2011-11-07 Impact factor: 2.802
Authors: Benjamin A Hilton; Ji Liu; Brian M Cartwright; Yiyong Liu; Maya Breitman; Youjie Wang; Rowdy Jones; Hui Tang; Antonio Rusinol; Phillip R Musich; Yue Zou Journal: FASEB J Date: 2017-05-17 Impact factor: 5.191
Authors: Md Sahab Uddin; Md Tanvir Kabir; Md Jakaria; Abdullah Al Mamun; Kamal Niaz; Md Shah Amran; George E Barreto; Ghulam Md Ashraf Journal: Neurotox Res Date: 2019-05-04 Impact factor: 3.911