Accelerated replicative senescence of medial smooth muscle cells derived from abdominal aortic aneurysms compared to the adjacent inferior mesenteric artery.
BACKGROUND
Abdominal aortic aneurysms (AAAs) are associated with aging and atherosclerosis. AAAs arise through a degenerative process characterized in part by depletion of medial smooth muscle cells (SMC), suggesting that generalized aging and SMC senescence represent potential mechanisms contributing to aneurysmal degeneration. It is not yet known whether SMC from AAA tissue exhibit a difference in proliferative capacity compared to SMC from nonaneurysmal vessels or to what extent such differences might be due to aging alone or other patient-specific factors.


METHODS
Aneurysm wall tissues were obtained from 15 patients undergoing AAA repair. In each case, a segment of the adjacent (nonaneurysmal) inferior mesenteric artery (IMA) from the same patient was used as a control. Paired AAA- and IMA-derived SMC strains were obtained by explant techniques and their proliferative capacities were compared during serial passage in culture.


RESULTS
Sustainable SMC cultures were established from all IMA explants but from only 9 of 15 AAAs (P < 0.05). The interval required to achieve primary explant growth was longer for AAAs than IMAs (16.4 +/- 2 vs 6.4 +/- 1 days; P < 0.001), but it was unrelated to patient age, gender, or aneurysm size. AAA-derived SMC appeared larger and rounder than the corresponding IMA-derived SMC, even after repeated passage in culture, and their maximal proliferation was reduced by 44.2 +/- 8% (n = 5 pairs, P < 0.05). Serum-stimulated [(3)H]thymidine uptake in AAA-derived SMC was also reduced by 54.9 +/- 7% (n = 5 pairs, P < 0.01), but flow cytometry revealed no differences in SMC viability, apoptosis, or necrosis. While IMA-derived SMC continued to proliferate beyond passage 20 during serial subculture, all AAA-derived SMC developed replicative senescence by passage 12.


CONCLUSIONS
AAA-derived SMC exhibit a distinct morphologic appearance in culture, a diminished proliferative capacity compared to SMC from the adjacent IMA, and a limited in vitro life span. These differences reflect an intrinsic alteration in SMC growth capacity independent of age alone. Tissue-specific processes leading to accelerated replicative senescence may therefore contribute to the selective medial SMC depletion observed in AAAs.
Liao
S
S
Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Curci
J A
JA
Kelley
B J
BJ
Sicard
G A
GA
Thompson
R W
RW
D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000166:cytology*; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D012995:Solubility
D017077:Culture Media, Conditioned; D006133:Growth Substances; D004247:DNA