Vitamin B6 protects vascular endothelial injury by activated platelets

SummaryBlood platelets provide the initial response to vascular endothelial injury, becoming activated as they adhere to the injured site. Activated platelets recruit leukocytes, and initiate proliferation and migration of vascular smooth muscle cells (SMC) within the injured vessel wall, leading to development of neointimal hyperplasia. Endothelial CD39/NTPDase1 and recombinant solCD39 rapidly metabolise nucleotides, including stimulatory ADP released from activated platelets, thereby suppressing additional platelet reactivity. Using a murine model of vascular endothelial injury, we investigated whether circulating human solCD39 could reduce platelet activation and accumulation, thus abating leukocyte infiltration and neointimal formation following vascular damage. Intraperitoneally-administered solCD39 ADP -ase activity in plasma peaked 1 hour (h) post-injection, with an elimination half-life of 43 h. Accordingly, mice were administered solCD39 or saline 1 h prior to vessel injury, then either sacrificed 24 h post-injury or treated with solCD39 or saline (three times weekly) for an additional 18 days. Twenty-four hours post-injury, solCD39-treated mice displayed a reduction in platelet activation and recruitment, P-selectin expression, and leukocyte accumulation in the arterial lumen. Furthermore, repeated administration of solCD39 modulated the late stage of vascular injury by suppressing leukocyte deposition, macrophage infiltration and smooth muscle cell (SMC) proliferation/migration, resulting in abrogation of neointimal thickening. In contrast, injured femoral arteries of saline-injected mice exhibited massive platelet thrombus formation, marked P-selectin expression, and leukocyte infiltration. Pronounced neointimal growth with macrophage and SMC accretion was also observed (intimal-to-medial area ratio 1.56 ± 0.34 at 19 days). Thus, systemic administration of solCD39 profoundly affects injury-induced cellular responses, minimising platelet deposition and leukocyte recruitment, and suppressing neointimal hyperplasia.

Download Full-text

In vitro study of vascular endothelial injury by activated platelets and its prevention

Atherosclerosis ◽

10.1016/0021-9150(89)90092-0 ◽

1989 ◽

Vol 76 (2-3) ◽

pp. 95-101 ◽

Cited By ~ 40

Author(s):

Yukio Kishi ◽

Fujio Numano

Keyword(s):

In Vitro Study ◽

Endothelial Injury ◽

Vitro Study ◽

Vascular Endothelial ◽

Activated Platelets

Download Full-text

Protective effect of pyridoxal phosphate against vascular endothelial injury by activated platelets

Atherosclerosis ◽

10.1016/0021-9150(94)93324-3 ◽

1994 ◽

Vol 109 (1-2) ◽

pp. 77

Author(s):

S.J. Chang

Keyword(s):

Protective Effect ◽

Pyridoxal Phosphate ◽

Endothelial Injury ◽

Vascular Endothelial ◽

Activated Platelets

Download Full-text

Hydroxyl Safflower Yellow Pigment A (HSYA) Improves Vascular Endothelial Injury Induced by Lipopolysaccharide In Vitro Study

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2596 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1792-1798

Author(s):

Li Yan ◽

Ge Jingping ◽

Yin Yuanyuan ◽

Li Xiaomei ◽

Zhao Boxiang ◽

...

Keyword(s):

Cell Proliferation ◽

In Vitro Study ◽

Treated Group ◽

Yellow Pigment ◽

Endothelial Injury ◽

Vitro Study ◽

Vascular Endothelial ◽

Treatment Groups ◽

Dose Dependent

Aim: This research was to investigate the effects and mechanisms of HSYA in vascular endothelial injury by vitro study. Methods: Dividing HUVECs as Normal Control (NC), Model (LPS treated) group, HSYA-L, HSYA-M and HSYA-H groups. Cells in the HSYA treatment groups were treated with LPS, followed by 40 mg/ml, 80 mg/ml, and 120 mg/ml HSYA intervention (HSYA-L, HSYA-M, and HSYA -H groups), respectively. Measuring the cell proliferation, apoptosis, relative proteins and mRNA (TLR4, MyD88 and NF-κB(p65)) expressions by MTT, Flow cytometry, WB and RT-qPCR assay. Using cellular immunofluorescence to evaluate NF-κB(p65) nuclear volume of difference groups. Results: With HSYA supplement, the cell proliferation rates were significantly up-regulation with cell apoptosis significantly down-regulation with TLR4 relatived mRNA and proteins and NF-κB(p65) nuclear significantly depressed with dose-dependent (P <0.05, respectively). Conclusion: HSYA improved vascular endothelial injury induced by LPS via TLR4 pathway In Vitro.

Download Full-text

Abstract 113: Regulation Of Aortic Vasodilation By Sigma-1 Receptor Stimulation In Ovariectomized And Pressure Overloaded Rats.

Circulation Research ◽

10.1161/res.113.suppl_1.a113 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Hideaki Tagashira ◽

Takayuki Matsumoto ◽

Kumiko Taguchi ◽

Tsuneo Kobayashi ◽

Kohji Fukunaga

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Pressure Overload ◽

Endothelial Injury ◽

Vascular Endothelial ◽

Aortic Banding ◽

Descending Aorta ◽

Sigma 1 Receptor ◽

Ovx Rats ◽

Sigma 1

Objective: We previously reported that sigma-1 receptor ( σ 1 R ) expression in the thoracic aorta decreased after pressure overload (PO) induced by abdominal aortic banding in ovariectomized (OVX) rats. Here, we asked whether stimulation of σ 1 R with the selective agonist SA4503 elicits functional recovery of aortic vasodilation and constriction following vascular injury in OVX rats with PO. Methods: SA4503 (0.3-1.0 mg kg -1 ) and NE-100 (an σ 1 R antagonist, 1.0 mg kg -1 ) were administered orally for 4 weeks (once daily) to OVX-PO rats, starting from the onset of aortic banding. Vascular functions of isolated descending aorta were measured following phenylephrine (PE)- or endothelin-1 (ET-1)-induced vasoconstriction and acetylcholine (ACh)- or clonidine-induced vasodilation. Results: σ 1 R expression in aortic smooth muscle and endothelial cells decreased significantly 4 weeks after PO in OVX rats (vs. Sham or OVX only group). SA4503 administration rescued PO-induced σ 1 R decreases in the descending aorta. SA4503 treatment also rescued PO-induced impairments in ACh- and clonidine-induced vasodilation without affecting PE- and ET-1-induced vasoconstriction. Ameliorated ACh- and clonidine-induced vasodilation was closely associated with increased Akt activity and in turn endothelial nitric oxide synthase (eNOS) phosphorylation. SA4503-mediated improvement of vasodilation was blocked by NE-100 treatment. Conclusions: σ 1 R is downregulated following PO-induced endothelial injury in OVX rats. The selective σ 1 R agonist SA4503 rescues impaired endothelium-dependent vasodilation in the aorta from OVX-PO rats through σ 1 R stimulation, enhancing eNOS-cGMP signaling in vascular endothelial cells. These observations encourage development of novel therapeutics targeting σ 1 R to prevent vascular endothelial injury in postmenopausal woman.

Download Full-text

Impaired Autophagy Induced by oxLDL/β2GPI/anti-β2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6662225 ◽

2021 ◽

Vol 2021 ◽

pp. 1-20

Author(s):

Guiting Zhang ◽

Chao He ◽

Qianqian Wu ◽

Guoying Xu ◽

Ming Kuang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Signaling Pathways ◽

Western Blotting ◽

Endothelial Injury ◽

Vascular Endothelial ◽

Endothelial Cell Dysfunction ◽

Western Blotting Analysis ◽

Cell Dysfunction ◽

Glycoprotein I

Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/β2GPI/anti-β2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/β2GPI/anti-β2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/β2GPI/anti-β2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.

Download Full-text