scholarly journals Sulodexide Reduces the Proinflammatory Effect of Serum from Patients with Peripheral Artery Disease in Human Arterial Endothelial Cells

2016 ◽  
Vol 40 (5) ◽  
pp. 1005-1012 ◽  
Author(s):  
Patrycja Sosińska ◽  
Ewa Baum ◽  
Beata Maćkowiak ◽  
Magdalena Maj ◽  
Katarzyna Sumińska-Jasińska ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Interleukin 1 ◽  
Secretory Activity ◽  
Dependent Manner ◽  
Peripheral Artery ◽  
Expression Of Genes ◽  
Artery Disease ◽  
Arterial Endothelial Cells

Background/Aims: Dysfunction of the arterial endothelial cells promotes the progression of atherosclerosis. We studied how exposure of human arterial endothelial cells to atherosclerotic serum from patients with peripheral artery disease changes the secretory activity of these cells, and whether that reaction is modified by sulodexide. Methods: Endothelial cells in in vitro culture were exposed to standard culture medium ± 100pg/mL Interleukin-1(IL-1) or to medium supplemented with 20% atherosclerotic serum. Afterwards, the expression of genes responsible for the synthesis of Interleukin-6 (IL-6), Vascular Cell Adhesion Protein-1 (VCAM-1) and Von Willebrand Factor (VWF) was evaluated, together with the secretion of these compounds. Additionally, the effect of sulodexide on these processes was studied. Results: Atherosclerotic serum stimulated the expression of IL6, VCAM-1 and VWF genes in endothelial cells, which was followed by increased secretion of these compounds by 179%, 121% and 116%, respectively. Sulodexide (0.5 LRU/mL) reduced atherosclerotic serum-induced increased expression of genes for IL-6 (-32%), VCAM-1 (-20%) and VWF (-42%), and lowered secretion of these molecules: IL-6 (-27%), VCAM-1(-27%), VWF (-25%). Sulodexide also reduced, in a dose- dependent manner, secretion of IL6 from unstimulated and stimulated with IL-1 endothelial cells. Conclusions: Atherosclerotic serum induces proinflammatory and prothrombotic phenotype in arterial endothelium, which is partially reduced by sulodexide, via inhibition of genes expression, and in consequence lower secretory activity.

scholarly journals Dual specificity phosphatase 5 regulates perfusion recovery in experimental peripheral artery disease

2019 ◽  
Vol 24 (5) ◽  
pp. 395-404 ◽  
Author(s):  
Satyanarayana Alleboina ◽  
Dawit Ayalew ◽  
Rahul Peravali ◽  
Lingdan Chen ◽  
Thomas Wong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Endothelial Cell Proliferation ◽  
Peripheral Artery ◽  
Vessel Occlusion ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Artery Disease

Peripheral artery disease (PAD) is caused by atherosclerotic occlusions of vessels outside the heart, particularly those of the lower extremities. Angiogenesis is one critical physiological response to vessel occlusion in PAD, but our understanding of the molecular mechanisms involved in angiogenesis is incomplete. Dual specificity phosphatase 5 (DUSP5) has been shown to play a key role in embryonic vascular development, but its role in post-ischemic angiogenesis is not known. We induced hind limb ischemia in mice and found robust upregulation of Dusp5 expression in ischemic hind limbs. Moreover, in vivo knockdown of Dusp5 resulted in impaired perfusion recovery in ischemic limbs and was associated with increased limb necrosis. In vitro studies showed upregulation of DUSP5 in human endothelial cells exposed to ischemia, and knockdown of DUSP5 in these ischemic endothelial cells resulted in impaired endothelial cell proliferation and angiogenesis, but did not alter apoptosis. Finally, we show that these effects of DUSP5 on post-ischemic angiogenesis are a result of DUSP5-dependent decrease in ERK1/2 phosphorylation and p21 protein expression. Thus, we have identified a role of DUSP5 in post-ischemic angiogenesis and implicated a DUSP5-ERK-p21 pathway that may serve as a therapeutic target for the modulation of post-ischemic angiogenesis in PAD.

Soluble CD40L in peripheral artery disease

2005 ◽  
Vol 93 (03) ◽  
pp. 578-583 ◽  
Author(s):  
Kiat Tan ◽  
Muzahir Tayebjee ◽  
Indran Davagnanam ◽  
Mark Moss ◽  
Gregory Lip ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Sole Source ◽  
Clinical Severity ◽  
Healthy Controls ◽  
Peripheral Artery ◽  
Platelet Surface ◽  
Soluble Cd40l ◽  
Soluble P ◽  
Artery Disease

SummaryAlthough soluble CD40L (sCD40L, possibly derived from platelets and pro-inflammatory in vitro) may be implicated in thrombosis and haemostasis, there are little data in peripheral artery disease (PAD). We hypothesised the following: (a) that sCD40L relates to the clinical severity of PAD; and (b) that peripheral artery angioplasty acutely raises sCD40L levels. sCD40L was compared to established platelet markers soluble P selectin, platelet microparticles and platelet surface expression of CD62 and CD63. We recruited 36 healthy controls, 33 patients with intermittent claudication (IC), and 33 with symptomatically more severe critical limb is chaemia (CLI), measuring plasma markers by ELISA and membrane markers by flow cytometry. Eleven patients with CLI subsequently underwent peripheral artery angioplasty: blood was taken before and 10 minutes after the intervention. Results show that sCD40L was raised in IC at median 68 (IQR 28–333) pg/ml and in CLI at 64 (34–282) pg/mL compared to 35 (IQR 28–55) pg/ml in the healthy controls (p=0.009). Levels were no different between IC and CLI. The same distribution pattern was present for soluble P selectin, %platelets CD62+ve and CD63+ve. sCD40L failed to correlate significantly with ABPI (p=0.264), unlike %platelets CD62+ve (p=0.0032) and CD63+ve (p=0.009). Pre-angioplasty sCD40L level of 72 (35–610) ng/ml rose to 100 ng/ml (IQR=60–237)(p=0.018) post–angioplasty. Plasma sCD40L, in addition to other platelet indices, is raised in peripheral atherosclerosis and is increased by peripheral artery angioplasty, although levels seem unrelated to clinical severity. Failure to correlate with other markers suggest the platelet may not be the sole source of sCD40L, and that other cells may contribute to plasma levels.

scholarly journals Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease

2018 ◽  
Author(s):  
Igor Giarretta ◽  
Ilaria Gatto ◽  
Margherita Marcantoni ◽  
Giulia Lupi ◽  
Diego Tonello ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Sonic Hedgehog ◽  
Crucial Role ◽  
Experimental Studies ◽  
Clinical Implications ◽  
Peripheral Artery ◽  
Circulating Microparticles ◽  
Artery Disease ◽  
And Control

Sonic Hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh+ MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. In this study, the plasma  number of Shh+ MPs in patients with peripheral artery disease (PAD) and control subjects without PAD. We found significantly higher number of Shh+ MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs – produced either by endothelial cells, platelets, leukocytes, and erythrocytes – was not different between PAD patients and controls. Interestingly, the concentration of Shh protein unbound to MPs – which was measured in MP-depleted plasma – was not different between subjects with PAD and controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel insights on the mechanisms through which the Shh signaling is reactivated during ischemia in humans, with potentially important fundamental and clinical implications.

scholarly journals Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease

2018 ◽  
Vol 19 (12) ◽  
pp. 3954 ◽  
Author(s):  
Igor Giarretta ◽  
Ilaria Gatto ◽  
Margherita Marcantoni ◽  
Giulia Lupi ◽  
Diego Tonello ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Sonic Hedgehog ◽  
Experimental Studies ◽  
Clinical Implications ◽  
Peripheral Artery ◽  
Circulating Microparticles ◽  
Artery Disease ◽  
Collateral Vessels ◽  
And Control

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.

scholarly journals Polyunsaturated fatty acids and peripheral artery disease

2012 ◽  
Vol 17 (1) ◽  
pp. 51-63 ◽  
Author(s):  
S Marlene Grenon ◽  
Millie Hughes-Fulford ◽  
Joseph Rapp ◽  
Michael S Conte
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Peripheral Artery Disease ◽  
In Vivo Studies ◽  
Peripheral Artery ◽  
Beneficial Effects ◽  
Epidemiological Surveys ◽  
Artery Disease

There is substantial evidence that polyunsaturated fatty acids (PUFAs) such as n-3 and n-6 fatty acids (FAs) play an important role in prevention of atherosclerosis. In vitro and in vivo studies focusing on the interactions between monocytes and endothelial cells have explored the molecular effects of FAs on these interactions. Epidemiological surveys, followed by large, randomized, control trials have demonstrated a reduction in major cardiovascular events with supplementation of n-3 FAs in secondary prevention settings. The evidence of beneficial effects specific to patients with peripheral artery disease (PAD) remains elusive, and is the focus of this review.

scholarly journals Tissue Factor Expression in Bovine Endothelial Cells Induced by Pasteurella haemolytica Lipopolysaccharide and Interleukin-1

1994 ◽  
Vol 31 (1) ◽  
pp. 55-60 ◽  
Author(s):  
M. A. Breider ◽  
Z. Yang
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Interleukin 1 ◽  
Cellular Tissue ◽  
Pasteurella Haemolytica ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Vascular Thrombosis ◽  
Factor Expression

Pasteurella haemolytica in cattle produces fibrinohemorrhagic pleuropneumonia characterized by extensive pulmonary microvascular thrombosis and parenchymal necrosis. The purpose of this in vitro study was to determine if P. haemolytica lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant state in vascular endothelial cells. After treatment of confluent monolayers of bovine pulmonary artery endothelial cells with various concentrations of either P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the endothelial cells was determined using a chromogenic assay dependent on cellular tissue factor expression. The LPS treatment induced significant increases in cellular tissue factor expression in a LPS concentration- and time-dependent manner. Highest levels of tissue factor were present at 22 hours after treatment, although high LPS concentrations induced moderate tissue factor levels at 5 hours after treatment. Interleukin-1 also induced tissue factor expression in endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect could be diminished by concurrent use of an interleukin-1 receptor antagonist. These results demonstrate that LPS and cytokine promotion of a procoagulant state in endothelial cells occurs in vitro. Similar mechanisms may play a role in P. haemolytica-mediated pulmonary vascular thrombosis.

scholarly journals Smoking and the Pathophysiology of Peripheral Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiming Wang ◽  
Tingting Zhao ◽  
Kang Geng ◽  
Gang Yuan ◽  
Yue Chen ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Vascular Diseases ◽  
Pathological Process ◽  
Peripheral Artery ◽  
Cell Remodeling ◽  
Artery Disease

Smoking is one of the most important preventable factors causing peripheral artery disease (PAD). The purpose of this review is to comprehensively analyze and summarize the pathogenesis and clinical characteristics of smoking in PAD based on existing clinical, in vivo, and in vitro studies. Extensive searches and literature reviews have shown that a large amount of data exists on the pathological process underlying the effects of cigarette smoke and its components on PAD through various mechanisms. Cigarette smoke extracts (CSE) induce endothelial cell dysfunction, smooth muscle cell remodeling and macrophage phenotypic transformation through multiple molecular mechanisms. These pathological changes are the molecular basis for the occurrence and development of peripheral vascular diseases. With few discussions on the topic, we will summarize recent insights into the effect of smoking on regulating PAD through multiple pathways and its possible pathogenic mechanism.

Loss of Id3 (Inhibitor of Differentiation 3) Increases the Number of IgM-Producing B-1b Cells in Ischemic Skeletal Muscle Impairing Blood Flow Recovery During Hindlimb Ischemia

2021 ◽  
Author(s):  
Victoria Osinski ◽  
Prasad Srikakulapu ◽  
Young Min Haider ◽  
Melissa A. Marshall ◽  
Vijay C. Ganta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
B Cell ◽  
Peripheral Artery Disease ◽  
Myeloid Cell ◽  
Hindlimb Ischemia ◽  
Peripheral Artery ◽  
Artery Ligation ◽  
Artery Disease

Objective: Neovascularization can maintain and even improve tissue perfusion in the setting of limb ischemia during peripheral artery disease. The molecular and cellular mechanisms mediating this process are incompletely understood. We investigate the potential role(s) for Id3 (inhibitor of differentiation 3) in regulating blood flow in a murine model of hindlimb ischemia (HLI). Approach and Results: HLI was modeled through femoral artery ligation and resection and blood flow recovery was quantified by laser Doppler perfusion imaging. Mice with global Id3 deletion had significantly impaired perfusion recovery at 14 and 21 days of HLI. Endothelial- or myeloid cell-specific deletion of Id3 revealed no effect on perfusion recovery while B-cell–specific knockout of Id3 (Id3 BKO ) revealed a significant attenuation of perfusion recovery. Flow cytometry revealed no differences in ischemia-induced T cells or myeloid cell numbers at 7 days of HLI, yet there was a significant increase in B-1b cells in Id3 BKO . Consistent with these findings, ELISA demonstrated increases in skeletal muscle and plasma IgM. In vitro experiments demonstrated reduced proliferation and increased cell death when endothelial cells were treated with conditioned media from IgM-producing B-1b cells and tibialis anterior muscles in Id3 BKO mice showed reduced density of total CD31 + and αSMA + CD31 + vessels. Conclusions: This study is the first to demonstrate a role for B-cell–specific Id3 in maintaining blood flow recovery during HLI. Results suggest a role for Id3 in promoting blood flow during HLI and limiting IgM-expressing B-1b cell expansion. These findings present new mechanisms to investigate in peripheral artery disease pathogenesis.

Corilagin Ameliorates Atherosclerosis in Peripheral Artery Disease via TLR4 Signal Pathway in vitro and in vivo

2019 ◽  
Author(s):  
Yi-Qing Li ◽  
Yu-Jie Wang ◽  
Yun-Fei Chen ◽  
Yao Wang ◽  
Shao-Jun Zhang ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Signal Pathway ◽  
Peripheral Artery ◽  
Artery Disease
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