The occurrence of cardiovascular diseases increases with age independent of other risk factors, and the percentage of senescent cells is significantly elevated in vascular cells at atherosclerotic sites. Patients with accelerated aging syndromes caused by mutant lamin A protein, a structural component in nuclear lamina, also share many similarities with normal aged people, including the propensity to develop atherosclerosis. Recent studies have revealed the accumulation of prelamin A in normal aged vascular cells, and that lamin A participated as a mechanosensitive molecule in regulating various cellular events. These findings suggest that the ectopic expression of mutant lamin A or lamin A precursor (prelamin A) not only causes defects in cell mechanics, but it also disturbs stress-induced mechanotransduction pathways involving lamin A, both of which may contribute to vascular dysregulation. This review summarizes the current understanding of how lamin proteins are involved in vascular cell during aging, with a particular focus on the effect of mechanical stresses from blood flow on nuclear lamina of endothelial cells. Related studies are clarifying the role of lamin A in the progression of atherosclerosis, which will aid in the development of potential therapies for those suffering from lamin A-associated accelerated aging syndromes.