Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum from Patients with Peripheral Artery Diseases

Abstract

Background/Aims: Aging of the arterial endothelial cells results in the appearance of their inflammatory phenotype, which may predispose patients to the acceleration of arteriosclerosis. We studied the effect of serum from patients with peripheral artery disease (PAD) on the senescence of human aortic endothelial cells (HAEC) and how that process is modulated by sulodexide. Methods: HAEC replicative aging in vitro was studied in the presence of 10% PAD-serum (PAD Group) or10%PAD serum and Sulodexide 0.5 LRU/mL (PAD-SUL group). In control group cells were cultured in medium supplemented with 10% fetal bovine serum. All studied parameters were evaluated at the beginning and at the end of the study, in all experimental groups. Population doubling time (PDT) was studied from the cells growth rate after repeated passages, and senescence-associated beta- galactosidase activity (SA-β gal activity) was measured with the fluorescence flow cytometry. Expression of IL6, vWF, p21 and p53 genes was measured with the real-time polymerase chain reaction (Real-Time PCR). Concentrations of IL6 and vWF were measured with the standard ELISA kits. Results: PAD serum accelerated the senescence of HAEC as reflected by increased, compared to control, expression of the IL6 gene (+43%, p<0.05) vWF gene (+443%, p<0.01), p21 gene (+ 124%, p<0.01) and p53 gene (+ 85%, p<0.01). Secretion of IL6 and vWF was higher in that group: + 101%, p<0.01 and + 78%, p<0.01, respectively, as compared to control. Also, SA-β gal activity was higher in the PAD group (+33%, p<0.05) than in the control group. In the PAD group PDT was longer (+108%, p<0.01) as compared to control. Simultaneous use of Sulodexide with PAD serum significantly reduced all the above described senescent changes in HAEC. Conclusions: PAD serum accelerates the aging of HAEC which may result in the faster progression of arteriosclerosis. Sulodexide reduces PAD induced senescence of HAEC, which results in lower inflammatory and thrombogenic activity of these cells.

Sulodexide reduces glucose induced senescence in human retinal endothelial cells

“…In a clinical 12-month study, Sulodexide was shown to slow the progression of non-proliferative diabetic retinopathy 22 . The presented results confirm the strong anti-senescent and anti-inflammatory effect of sulodexide in microvascular retinal endothelial cells, which was shown previously in venous 12 , 23 and arterial 13 endothelial cells. The senescent phenotype of retinal endothelial cells predisposes patients to abnormal, excessive growth of retinal microvessels and pathological neovascularization, leading to vitreous haemorrhages 8 .…”

“…Therefore, inhibition of retinal endothelial senescence may be an effective way of slowing the progress of diabetic retinopathy 11 . Previously, we found that senescence of human venous and arterial endothelial cells was slowed down by Sulodexide, which is a mixture of glycosaminoglycans: low molecular-weight heparin and dermatan sulphate 12 , 13 . Sulodexide also reduced glucose toxicity towards human venous endothelial cells 14 .…”

Cellular Senescence in Arterial Diseases

“… 57 Serum from PAD patients showed acceleration in the aging phenotype of HAECs. 58 This was suppressed by administering sulodexide (a mixture of glycosaminoglycans). 58 The results of that study indicate that serum from PAD patients contains pro-senescent molecules that accelerate arteriosclerosis.…”

“… 58 This was suppressed by administering sulodexide (a mixture of glycosaminoglycans). 58 The results of that study indicate that serum from PAD patients contains pro-senescent molecules that accelerate arteriosclerosis. 58 However, to date, few studies have investigated the role of cellular senescence in PAD or the role of senescence processes in VSMCs specifically.…”

Sulodexide may be a real alternative to low molecular weight heparins in the prevention of COVID ‐19 induced vascular complications

“…7 Biological activity comprises arterial and venous antithrombotic and profibrinolytic (increased tissue plasminogen activator level, inhibition of platelet aggregation), antiinflammatory (eg, suppressed interleukin-6 production) and beneficial hemorheologic (lipid profile modification) effects. 7 SDX protects and repairs endothelial layer by glycocalyx restoration and vascular tone regulation, 7,8 displays senolytic activity, 9 and attenuates ischemia-reperfusion injury. 7 Compared with LMWHs it is less likely associated with bleeding risk, much weaker in HIT and renal insufficiency does not demand dose reduction.…”