Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes

Gerdes, Norbert; Seijkens, Tom; Lievens, Dirk; Kuijpers, Marijke J. E.; Winkels, Holger; Projahn, Delia; Hartwig, Helene; Beckers, Linda; Megens, Remco T. A.; Boon, Louis; Noelle, Randolph J.; Soehnlein, Oliver; Heemskerk, Johan W. M.; Weber, Christian; Lutgens, Esther

doi:10.1161/atvbaha.115.307074

Cited by 92 publications

(85 citation statements)

References 57 publications

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“…Interestingly, platelet:PMN aggregates formed during inflammation lead to SPM biosynthesis, which have been shown to reduce human platelet:PMN aggregates 119, 120 . Given that platelet:PMN aggregates contribute to plaque inflammation 121 , these results highlight that SPM may have additional protective roles in regulating PMN activation during inflammation associated with atherosclerosis.…”

Section: Cellular Actions Of Resolvins In the Context Of Cvdmentioning

confidence: 86%

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Sansbury

Spite

2016

Circulation Research

166

103

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Acute inflammation is a host-protective response that is mounted in response to tissue injury and infection. Initiated and perpetuated by exogenous and endogenous mediators, acute inflammation must be resolved for tissue repair to proceed and for homeostasis to be restored. Resolution of inflammation is an actively regulated process governed by an array of mediators as diverse as those that initiate inflammation. Among these, resolvins have emerged as a genus of evolutionarily conserved pro-resolving mediators that act on specific cellular receptors to regulate leukocyte trafficking and blunt production of inflammatory mediators, while promoting clearance of dead cells and tissue repair. Given that chronic unresolved inflammation is emerging as a central causative factor in the development of cardiovascular diseases, an understanding of the endogenous processes that govern normal resolution of acute inflammation is critical for determining why sterile maladaptive cardiovascular inflammation perpetuates. Here, we provide an overview of the process of resolution with a focus on the enzymatic biosynthesis and receptor-dependent actions of resolvins and related pro-resolving mediators in immunity, thrombosis and vascular biology. We discuss how nutritional and current therapeutic approaches modulate resolution and propose that harnessing resolution concepts could potentially lead to the development of new approaches for treating chronic cardiovascular inflammation in a manner that is not host-disruptive.

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Section: Cellular Actions Of Resolvins In the Context Of Cvdmentioning

confidence: 86%

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Sansbury

Spite

2016

Circulation Research

166

103

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“…The CD40 is the receptor for CD40L, being present in platelets. Gerdes et al 17 have demonstrated in knockout mice for CD40 and ApoE that platelet plays a crucial role in inflammation by stimulating leukocyte and endothelial cells activation, thereby promoting atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent

Farsky¹,

Hirata²,

Arnoni³

et al. 2018

Arquivos Brasileiros De Cardiologia

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BackgroundStudies have pointed out a higher mortality after coronary artery bypass surgery (CABG) in patients with stent.ObjectiveTo evaluate inflammatory markers in peripheral blood cells and in coronary artery tissue samples obtained during CABG in patients with stent compared to controls.MethodsThe case series consisted of two groups, one with previous stent implantation (n = 41) and one control (n = 26). The expression of the LIGHT, IL-6, ICAM, VCAM, CD40, NFKB, TNF, IFNG genes was analyzed in peripheral blood cells collected preoperatively. The coronary artery was evaluated for: interleukin-6, ICAM, VCAM, CD40, NFKB, TNF-alpha and IFN-gamma by immunohistochemistry. A total of 176 tissue samples were grouped for analysis in: A1- arteries with stent (n = 38); A2- native arteries from patients with stent in another artery (n = 68); and A3- arteries without stent from controls undergoing routinely CABG surgery (n = 70). A significance level of 0.05 was adopted.ResultsPatients with stent showed higher TNF (p = 0.03) and lower CD40 gene expression (p = 0.01) in peripheral blood cells than controls without stent. In coronary artery samples, the TNF-alpha protein staining was higher in the group A1, not only in the intima-media layer (5.16 ± 5.05 vs 1.90 ± 2.27; p = 0.02), but also in the adipose tissue (6.69 ± 3.87 vs 2.27 ± 4.00; p < 0.001). Furthermore, group A1 had a higher interleukin-6 protein staining in adipose tissue than group A3 (p = 0.04).ConclusionWe observed a persistently higher systemic TNF expression associated with exacerbated TNF-alpha and interleukin-6 local production in patients with stents. This finding may contribute to a worse clinical outcome.

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“…Platelet CD40 stimulates activations of leukocyte and endothelial cells and further promotes atherosclerosis [108]. Meanwhile, increased MMP-2 activity potentiates inflammation insults and plaque instability in the injured vascular wall [109].…”

Section: Effects Of S Miltiorrhiza and Its Isolated Compounds On Thementioning

confidence: 99%

Salvia miltiorrhiza: A Potential Red Light to the Development of Cardiovascular Diseases

Wang

Liu

et al. 2017

CPD

190

125

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Salvia miltiorrhiza Bunge, also known as Danshen in Chinese, has been widely used to treat cardiovascular diseases (CVD) in China and other Asia countries. Here, we summarize literatures of the historical traditional Chinese medicine (TCM) interpretation of the action of Salvia miltiorrhiza, its use in current clinical trials, its main phytochemical constituents and its pharmacological findings by consulting Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, and the Web of Science Databases. Since 2000, 39 clinical trials have been identified that used S. miltiorrhiza in TCM prescriptions alone or with other herbs for the treatment of patients with CVD. More than 200 individual compounds have been isolated and characterized from S. miltiorrhiza, which exhibited various pharmacological activities targeting different pathways for the treatment of CVD in various animal and cell models. The isolated compounds may provide new perspectives in alternative treatment regimes and reveal novel chemical scaffolds for the development of anti-CVD drugs. Meanwhile, there are also some rising concerns of the potential side effects and drug-drug interactions of this plant. The insights gained from this study will help us to better understanding of the actions of this herb for management of cardiovascular disorders. As an herb of red root, S. miltiorrhiza will act as a potential red light to prevent the development of CVD.

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Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes

Cited by 92 publications

References 57 publications

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent

Salvia miltiorrhiza: A Potential Red Light to the Development of Cardiovascular Diseases

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