Age-related increase of stem marker expression influences vascular smooth muscle cell properties

作者：Ferlosio Amedeo; Arcuri Gaetano; Doldo Elena; Scioli Maria Giovanna; De Falco Sandro; Spagnoli Luigi Giusto; Orlandi Augusto^*

来源：Atherosclerosis, 2012, 224(1): 51-57.

DOI：10.1016/j.atherosclerosis.2012.07.016

• Aging
• Smooth muscle cells
• Flt-1
• c-Kit
• alpha-Smooth muscle actin
• Atherosclerosis

Objective: Aging represents a major risk factor for vascular disease development. With aging, changes of the biological properties of vascular smooth muscle cells (SMCs) are observed. Stem marker expression characterizes SMCs during developmental growth and atherosclerosis, but the contribution of SMCs with stem features to the age-related arterial remodeling remains largely unknown. %26lt;br%26gt;Methods and results: Immunostaining revealed rare vascular growth factor receptor-1(+) (flt-1(+)) and c-kit(+) cells in tunica media of grossly normal human young (17-30 years old) large arteries and 2-month old rat aorta, whereas CD133(+) cells were absent. In large arteries of human aged donors (64-77 years), flt-1(+) and c-kit(+) cell number increased in the intimal thickening and tunica media. Double immunofluorescence revealed that 30.6 +/- 3% of flt-1(+) intimal cells co-expressed alpha-smooth muscle actin. Immunostaining, blots and RT-PCR documented the increased expression of flt-1 and c-kit in 20-24-month old rat aortic media. In vitro, old rat aortic SMCs proliferated and migrated more with greater flt-1, c-kit, NF-kappa B, VCAM-1, IAP-1 and MCP-1 levels and less alpha-smooth muscle actin and myosin compared to young SMCs. Old SMCs were also more susceptible to all-trans retinoic and NF-kappa B inhibition-induced apoptosis compared to young SMCs. Anti-flt-1 blocking antibody reduced migration and placental growth factor-induced but not serum and PDGF-BB-stimulated proliferation of old SMCs. %26lt;br%26gt;Conclusions: The increase of flt-1(+) and c-kit(+) SMCs characterizes large arteries of aged donors; the blocking of flt-1 signaling influences the behavior of old SMCs, suggesting that the accumulation of SMCs with a stem phenotype contributes to the age-dependent adverse arterial remodeling.

• 出版日期2012-9