A-type lamins and cardiovascular disease in premature aging syndromes

- A-type lamins (LMNA gene) play important structural and regulatory roles.
- Multiple diseases arise from LMNA mutations, including progeroid syndromes.
- Premature death in progeria is caused by severe cardiovascular disease.
- Diverse mechanisms perturb cellular and whole-body homeostasis in progeria.
- Additional progeria-causing mechanisms remain unknown.

Lamin A is a nuclear intermediate filament protein with important structural and regulatory roles in most differentiated mammalian cells. Excessive accumulation of its precursor prelamin A or the mutant form called 'progerin' causes premature aging syndromes. Progeroid 'laminopathies' are characterized by severe cardiovascular problems (cardiac electrical defects, vascular calcification and stiffening, atherosclerosis, myocardial infarction, and stroke) and premature death. Here, we review studies in cell and mouse models and patients that are unraveling how abnormal prelamin A and progerin accumulation accelerates cardiovascular disease and aging. This knowledge is essential for developing effective therapies to treat progeria and may help identify new mechanisms underlying normal aging.