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Sulodexide reduces senescence-related changes in human endothelial cells.

Suminska-Jasinska K, Polubinska A, Ciszewicz M, Mikstacki A, Antoniewicz A, Breborowicz A - Med. Sci. Monit. (2011)

Bottom Line: Changes in population doubling time and beta-galactosidase activity were used as indexes of aging and compared with other cellular parameters.Sulodexide prevented cellular senescence in cultured endothelial cells, moderating features of the cellular senescence in endothelial cells in in vitro conditions, which potentially may have practical application.The administration of sulodexide could potentially be used in prevention of atherosclerotic changes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.

ABSTRACT

Background: Senescent endothelial cells acquire functional properties that make the vascular wall more prone to atherosclerotic changes. We tested whether senescence of the endothelial cells maintained in in vitro culture can be moderated by their simultaneous exposure to sulodexide.

Material/methods: Replicative aging of the endothelial cells was studied during their 15 passages performed every 4 days in cells cultured in standard medium or in medium supplemented with sulodexide 0.5 LRU/mL. Changes in population doubling time and beta-galactosidase activity were used as indexes of aging and compared with other cellular parameters.

Results: Repeated passages of endothelial cells induce their senescence, as reflected by prolongation of the population doubling time, increased beta-galactosidase activity, oxidative stress and release of cytokines. Healing of the injured endothelial monolayer is impaired in senescent cells. Sulodexide partially prevents oxidative stress and totally eliminates other senescence-related changes such as increased release of MCP-1, lengthening of the population doubling time, and impaired healing of the cellular monolayer after its mechanical injury.

Conclusions: Sulodexide prevented cellular senescence in cultured endothelial cells, moderating features of the cellular senescence in endothelial cells in in vitro conditions, which potentially may have practical application. The administration of sulodexide could potentially be used in prevention of atherosclerotic changes.

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Related in: MedlinePlus

Unstimulated synthesis of interleukin-6 (IL-6) – (A) and monocyte chemoattractant protein -1 (MCP-1) – (B) in endothelial cells at the beginning of the experiment (START) and after 15 passages in control medium (CON-END) or in medium supplemented with sulodexide 0.5 LRU/mL (SUL-END).
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f3-medscimonit-17-4-cr222: Unstimulated synthesis of interleukin-6 (IL-6) – (A) and monocyte chemoattractant protein -1 (MCP-1) – (B) in endothelial cells at the beginning of the experiment (START) and after 15 passages in control medium (CON-END) or in medium supplemented with sulodexide 0.5 LRU/mL (SUL-END).

Mentions: Cells from the control group demonstrated signs of hypertrophy during replicative aging: 237±61 μg protein/105 cells at the beginning of experiment and 487±119 μg protein/105 cells at the end (p<0.01). However, in the presence of sulodexide, hypertrophy of the cells at the end of the experiment, despite some increase, was not significantly different from at the beginning of the study: 351±86 μg protein/105 cells (n.s.). Population doubling time was increased at the end of the experiment in the control group, but in cells treated with sulodexide its value was comparable to that at the beginning of the study. Positive staining for β-galactosidase increased during replicative aging in both studied groups, but that increase was significantly weaker in the sulodexide-treated cells (Figure 1). Replicative aging resulted in increased oxidative stress in both studied groups, but in cells exposed to sulodexide oxidative stress was weaker (−35%, p<0.01) than in the control group (Figure 2). Healing of the mechanically injured endothelial layer was slower in control cells exposed to replicative aging, but healing of the endothelial cells monolayer was not affected by aging when these cells were exposed to sulodexide (Figure 2). Replicative aging of the control cells resulted in increased spontaneous release of IL-6 and MCP-1 (Figure 3). In the presence of sulodexide, only spontaneous release of IL-6 was enhanced at the end of the experiment, but it was still lower than in the control group (−47%, p<0.01). Cells treated with sulodexide did not show increased release of MCP-1 during replicative aging (Figure 3).


Sulodexide reduces senescence-related changes in human endothelial cells.

Suminska-Jasinska K, Polubinska A, Ciszewicz M, Mikstacki A, Antoniewicz A, Breborowicz A - Med. Sci. Monit. (2011)

Unstimulated synthesis of interleukin-6 (IL-6) – (A) and monocyte chemoattractant protein -1 (MCP-1) – (B) in endothelial cells at the beginning of the experiment (START) and after 15 passages in control medium (CON-END) or in medium supplemented with sulodexide 0.5 LRU/mL (SUL-END).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539523&req=5

f3-medscimonit-17-4-cr222: Unstimulated synthesis of interleukin-6 (IL-6) – (A) and monocyte chemoattractant protein -1 (MCP-1) – (B) in endothelial cells at the beginning of the experiment (START) and after 15 passages in control medium (CON-END) or in medium supplemented with sulodexide 0.5 LRU/mL (SUL-END).
Mentions: Cells from the control group demonstrated signs of hypertrophy during replicative aging: 237±61 μg protein/105 cells at the beginning of experiment and 487±119 μg protein/105 cells at the end (p<0.01). However, in the presence of sulodexide, hypertrophy of the cells at the end of the experiment, despite some increase, was not significantly different from at the beginning of the study: 351±86 μg protein/105 cells (n.s.). Population doubling time was increased at the end of the experiment in the control group, but in cells treated with sulodexide its value was comparable to that at the beginning of the study. Positive staining for β-galactosidase increased during replicative aging in both studied groups, but that increase was significantly weaker in the sulodexide-treated cells (Figure 1). Replicative aging resulted in increased oxidative stress in both studied groups, but in cells exposed to sulodexide oxidative stress was weaker (−35%, p<0.01) than in the control group (Figure 2). Healing of the mechanically injured endothelial layer was slower in control cells exposed to replicative aging, but healing of the endothelial cells monolayer was not affected by aging when these cells were exposed to sulodexide (Figure 2). Replicative aging of the control cells resulted in increased spontaneous release of IL-6 and MCP-1 (Figure 3). In the presence of sulodexide, only spontaneous release of IL-6 was enhanced at the end of the experiment, but it was still lower than in the control group (−47%, p<0.01). Cells treated with sulodexide did not show increased release of MCP-1 during replicative aging (Figure 3).

Bottom Line: Changes in population doubling time and beta-galactosidase activity were used as indexes of aging and compared with other cellular parameters.Sulodexide prevented cellular senescence in cultured endothelial cells, moderating features of the cellular senescence in endothelial cells in in vitro conditions, which potentially may have practical application.The administration of sulodexide could potentially be used in prevention of atherosclerotic changes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.

ABSTRACT

Background: Senescent endothelial cells acquire functional properties that make the vascular wall more prone to atherosclerotic changes. We tested whether senescence of the endothelial cells maintained in in vitro culture can be moderated by their simultaneous exposure to sulodexide.

Material/methods: Replicative aging of the endothelial cells was studied during their 15 passages performed every 4 days in cells cultured in standard medium or in medium supplemented with sulodexide 0.5 LRU/mL. Changes in population doubling time and beta-galactosidase activity were used as indexes of aging and compared with other cellular parameters.

Results: Repeated passages of endothelial cells induce their senescence, as reflected by prolongation of the population doubling time, increased beta-galactosidase activity, oxidative stress and release of cytokines. Healing of the injured endothelial monolayer is impaired in senescent cells. Sulodexide partially prevents oxidative stress and totally eliminates other senescence-related changes such as increased release of MCP-1, lengthening of the population doubling time, and impaired healing of the cellular monolayer after its mechanical injury.

Conclusions: Sulodexide prevented cellular senescence in cultured endothelial cells, moderating features of the cellular senescence in endothelial cells in in vitro conditions, which potentially may have practical application. The administration of sulodexide could potentially be used in prevention of atherosclerotic changes.

Show MeSH
Related in: MedlinePlus