PMID- 30964194
OWN - NLM
STAT- MEDLINE
DCOM- 20200825
LR  - 20200825
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 6
DP  - 2019 Mar
TI  - Sulodexide counteracts endothelial dysfunction induced by metabolic or 
      non-metabolic stresses through activation of the autophagic program.
PG  - 2669-2680
LID - 17415 [pii]
LID - 10.26355/eurrev_201903_17415 [doi]
AB  - OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and 
      post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide 
      (SDX) is a highly purified glycosaminoglycan with antithrombotic, 
      pro-fibrinolytic and anti-inflammatory activity used in the treatment of chronic 
      venous disease (CVD), including patients with PTS. SDX has recently obtained 
      clinical evidence in the "extension therapy" after initial-standard anticoagulant 
      treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). 
      Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human 
      umbilical vein endothelial cells (HUVEC) were used. Metabolic and non 
      metabolic-induced ED was induced by treating with methylglyoxal (MGO) or 
      irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The 
      production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for 
      cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot 
      analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC 
      from MGO- or IR-induced apoptosis by counteracting the activation of the 
      intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX 
      resulted from a reduction in a) ROS production, b) neo-synthesis and release of 
      pro-inflammatory cytokines (TNFalpha, IL1, IL6, IL8), c) DNA damage induced by MGO or 
      IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data 
      herein collected indicate the ability of SDX to counteract ED induced by 
      metabolic or non-metabolic stresses by involving the intracellular autophagy 
      pathway. Our experience significantly increases the knowledge of the mechanisms 
      of action of SDX against ED and supports the use of SDX in the treatment of CVD, 
      PTS and in the secondary prevention of recurrent DVT.
FAU - De Felice, F
AU  - De Felice F
AD  - Department of Radiotherapy, "Sapienza" University of Rome, Rome, Italy. 
      f.marampon@gmail.com.
FAU - Megiorni, F
AU  - Megiorni F
FAU - Pietrantoni, I
AU  - Pietrantoni I
FAU - Tini, P
AU  - Tini P
FAU - Lessiani, G
AU  - Lessiani G
FAU - Mastroiacovo, D
AU  - Mastroiacovo D
FAU - Mattana, P
AU  - Mattana P
FAU - Antinozzi, C
AU  - Antinozzi C
FAU - Di Luigi, L
AU  - Di Luigi L
FAU - Delle Monache, S
AU  - Delle Monache S
FAU - Angelucci, A
AU  - Angelucci A
FAU - Festuccia, C
AU  - Festuccia C
FAU - Fanzani, A
AU  - Fanzani A
FAU - Maggio, R
AU  - Maggio R
FAU - Tombolini, V
AU  - Tombolini V
FAU - Gravina, G L
AU  - Gravina GL
FAU - Marampon, F
AU  - Marampon F
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Cytokines)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Reactive Oxygen Species)
RN  - 722KLD7415 (Pyruvaldehyde)
RN  - 75HGV0062C (glucuronyl glucosamine glycan sulfate)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Cytokines/genetics/metabolism
MH  - Glycosaminoglycans/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells/*cytology/drug 
      effects/metabolism/radiation effects
MH  - Humans
MH  - Models, Biological
MH  - Pyruvaldehyde/*adverse effects
MH  - Reactive Oxygen Species/metabolism
MH  - X-Rays/*adverse effects
EDAT- 2019/04/10 06:00
MHDA- 2020/08/26 06:00
CRDT- 2019/04/10 06:00
PHST- 2019/04/10 06:00 [entrez]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2020/08/26 06:00 [medline]
AID - 17415 [pii]
AID - 10.26355/eurrev_201903_17415 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2669-2680. doi: 
      10.26355/eurrev_201903_17415.