Platelets, Inflammation and Cardiovascular Diseases. New Concepts and Therapeutic Implications

Gawaz, Meinrad; Favaloro, Emmanuel J.

doi:10.1055/s-0030-1251495

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Platelets are the cellular mediator of thrombosis, but it is becoming increasingly evident that platelets actively participate in inflammation and immune responses (1)(2)(3)(4)(5). Platelets either initiate or accelerate the immune response in diverse inflammatory diseases, including atherosclerosis, arthritis, cerebral malaria, and transplant rejection (1,4,(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection

Shi

Field

et al. 2014

J. Clin. Invest.

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Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development, which is important in many diseases, in addition to transplantation.

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Section: Introductionmentioning

confidence: 99%

Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection

Shi

Field

et al. 2014

J. Clin. Invest.

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“…Platelets play a role not only in normal hemostasis and thrombosis but also in the onset and progression of atherosclerosis, the underlying cause of cardiovascular disease and stroke [9,10]. Evidence for the importance of platelets in the development of atherosclerosis was first observed in a prospective study showing an association between platelet number and aggregability and long-term fatal coronary artery disease [11].…”

Section: Introductionmentioning

confidence: 99%

Platelet activation in chronic cocaine users: Effect of short term abstinence

Pereira¹,

Sáez²,

Pallavicini³

et al. 2011

Platelets

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Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20-54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks' abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p< 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.

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“…Beyond their known role in homeostasis, platelets have been proposed to contribute to acute and chronic inflammatory pathologies, including atherosclerosis and atherothrombosis in the later stages of the disease ( 184 , 185 ). Key mechanism of platelets that promote inflammation include the adhesion to the injured endothelium, leukocyte activation, and the formation of leukocyte-platelet aggregates ( 186 ).…”

Section: Trafs In Platelet Function and Homeostasismentioning

confidence: 99%

The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis

Gissler

Stachon

Wolf

et al. 2022

Front. Cardiovasc. Med.

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TNF receptor associated factors (TRAFs) represent a family of cytoplasmic signaling adaptor proteins that regulate, bundle, and transduce inflammatory signals downstream of TNF- (TNF-Rs), interleukin (IL)-1-, Toll-like- (TLRs), and IL-17 receptors. TRAFs play a pivotal role in regulating cell survival and immune cell function and are fundamental regulators of acute and chronic inflammation. Lately, the inhibition of inflammation by anti-cytokine therapy has emerged as novel treatment strategy in patients with atherosclerosis. Likewise, growing evidence from preclinical experiments proposes TRAFs as potent modulators of inflammation in atherosclerosis and vascular inflammation. Yet, TRAFs show a highly complex interplay between different TRAF-family members with partially opposing and overlapping functions that are determined by the level of cellular expression, concomitant signaling events, and the context of the disease. Therefore, inhibition of specific TRAFs may be beneficial in one condition and harmful in others. Here, we carefully discuss the cellular expression and signaling events of TRAFs and evaluate their role in vascular inflammation and atherosclerosis. We also highlight metabolic effects of TRAFs and discuss the development of TRAF-based therapeutics in the future.

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Platelets, Inflammation and Cardiovascular Diseases. New Concepts and Therapeutic Implications

Cited by 8 publications

References 32 publications

Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection

Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection

Platelet activation in chronic cocaine users: Effect of short term abstinence

The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis

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