Laminopathies and atherosclerosis.
Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. Some laminopathies affect the cardiovascular system, and a few (namely, Dunnigan-type familial partial lipodystrophy [FPLD2] and Hutchinson-Gilford progeria syndrome [HGPS]) feature atherosclerosis as a key component. The premature atherosclerosis of FPLD2 is probably related to characteristic proatherogenic metabolic disturbances such as dyslipidemia, hyperinsulinemia, hypertension, and diabetes. In contrast, the premature atherosclerosis of HGPS occurs with less exposure to metabolic proatherogenic traits and probably reflects the generalized process of accelerated aging in HGPS. Although some common polymorphisms of LMNA have been associated with traits related to atherosclerosis, the monogenic diseases FPLD2 and HGPS are more likely to provide clues about new pathways for the general process of atherosclerosis. Dunnigan-type familial partial lipodystrophy and Hutchinson-Gilford progeria syndrome are laminopathies caused by mutation in LMNA that feature atherosclerosis, which is related to proatherogenic metabolic disturbances and to the generalized process of accelerated aging, respectively. These monogenic diseases may provide clues about new pathways for atherogenesis.
Al-Shali
Khalid Z
KZ
Robarts Research Institute and University of Western Ontario, London, Canada.
Hegele
Robert A
RA
D000328:Adult; D017668:Age of Onset; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics; D003923:Diabetes Mellitus, Lipoatrophic / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D006973:Hypertension / Q000235:genetics; D007223:Infant; D007333:Insulin Resistance / Q000235:genetics; D034904:Lamin Type A / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009685:Nuclear Envelope / Q000648:ultrastructure; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011371:Progeria / Q000235:genetics / Q000378:metabolism
D034904:Lamin Type A; C440308:lamin C