Perspective: Collagen induced platelet activation the GPVI receptor as a primary target of colchicine in cardiovascular disease.

Colchicine has been demonstrated to reduce cardiovascular death, myocardial infarction (MI), ischemic stroke, and ischemia-driven coronary revascularization in people with coronary artery disease (CAD). These reductions were observed even in patients already taking antiplatelet therapy. As well as having anti-inflammatory effects, colchicine demonstrates antiplatelet effects.

Colchicine as a Modulator of Platelet Function: A Systematic Review.

The microtubule inhibitor and anti-inflammatory agent colchicine is used to treat a range of conditions involving inflammasome activation in monocytes and neutrophils, and is now known to prevent coronary and cerebrovascular events. In vitro studies dating back more than 50 years showed a direct effect of colchicine on platelets, but as little contemporary attention has been paid to this area, we have critically reviewed the effects of colchicine on diverse aspects of platelet biology in vitro and in vivo. In this systematic review we searched Embase, Medline, and PubMed for articles testing platelets after incubation with colchicine and/or reporting a clinical effect of colchicine treatment on platelet function, including only papers available in English and excluding reviews and conference abstracts.

Identification of a Distinct Platelet Phenotype in the Elderly: ADP Hypersensitivity Coexists With Platelet PAR (Protease-Activated Receptor)-1 and PAR-4-Mediated Thrombin Resistance.

Background: Thrombin (via PAR [protease-activated receptor]-1 and PAR-4) and ADP (via P2Y receptors) are potent endogenous platelet activators implicated in the development of cardiovascular disease. We aimed to assess whether platelet pathways alter with aging.

Methods: We characterized platelet activity in community-dwelling volunteers (n=174) in the following age groups: (1) 20 to 30 (young); (2) 40 to 55 (middle-aged); (3) ≥70 years (elderly).

Circulating platelet-derived extracellular vesicles are decreased after remote ischemic preconditioning in patients with coronary disease: A randomized controlled trial.

Background: Brief nonharmful ischemia, remote ischemic preconditioning (RIPC) has been proposed to confer benefit to patients with coronary artery disease via unknown mechanisms.

Objectives: We aimed to investigate the effect of RIPC on circulating levels of extracellular vesicles (EVs) and global coagulation and fibrinolytic factors in patients with coronary disease.

Patients/methods: Blood samples were taken from 60 patients presenting for coronary angiography enrolled in a randomized, controlled trial before and after RIPC (3 × 5 min administration of 200 mmHg sphygmomanometer on the arm, n = 31) or sham (n = 29) treatment.

Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase.

Objective:  Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.

Remote ischemic preconditioning inhibits platelet α β activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial.

Objectives: We investigated whether remote ischemic preconditioning (RIPC) inhibits agonist-induced conformational activation of platelet α β in patients with coronary artery disease already receiving conventional antiplatelet therapy.

Patients/methods: Consecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham.

Thrombin Generation and Cancer: Contributors and Consequences.

The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects.

Procoagulant Effects of Low-Level Platelet Activation and Its Inhibition by Colchicine.

Platelets play an important role in diseases such as cardiovascular disease and cancer, especially through their release of extracellular vesicles (EVs) and role in thrombosis. The effects of the anti-inflammatory drug colchicine on platelets are not well understood. We investigated the effect of colchicine on the release of pro-coagulant EVs from platelets under low-level activation.

Natural history of hypercoagulability in patients undergoing coronary revascularization and effect of preoperative myocardial infarction.

Objectives: The balance between hyper- and hypocoagulable states is critical after coronary artery surgery both with (coronary artery bypass grafting [CABG]) and without (off-pump coronary artery bypass [OPCAB]) cardiopulmonary bypass to prevent thrombotic or bleeding complications. We aimed to quantify novel parameters of coagulation, fibrinolysis, and overall hemostasis ≤6 months after CABG and OPCAB and to determine the influences on these parameters.

Methods: A total of 63 patients (30 CABG, 33 OPCAB) had blood collected before and at various points ≤6 months after surgery.

Tropoelastin modulates TGF-β1-induced expression of VEGF and CTGF in airway smooth muscle cells.

Elastin is predominantly comprised of crosslinked tropoelastin. For many years elastin was considered to serve a solely structural role but is now being increasingly identified as causal in cell signaling, development and repair. We introduced tropoelastin into an in vitro model in which airway smooth muscle cells (ASMCs) were stimulated with transforming growth factor (TGF)-β1 to examine the modulatory effect of this modular elastin sequence on release of angiogenic factors and matrix metalloproteinases (MMPs).

Detection of hypofibrinolysis in stable coronary artery disease using the overall haemostatic potential assay.

Introduction: Patients with stable coronary artery disease (CAD) are at risk of arterial thrombosis causing myocardial infarction. Detection of global haemostatic markers of hypercoagulability and hypofibrinolysis may be important for risk stratification and individualised treatment. We examined overall haemostatic potential (OHP) and thrombin generation in a group of stable CAD patients.

Off-pump coronary artery bypass surgery induces prolonged alterations to host neutrophil physiology.

Persistent alteration to host polymorphonuclear cell (PMN) physiology has been demonstrated after cardiac surgery performed with cardiopulmonary bypass (CPB). However, to date, PMN physiology and function beyond the first 24 h have not been investigated after cardiac surgery performed without CPB (off-pump coronary artery bypass grafting [OPCAB]). Blood samples of 15 patients were collected preoperatively and on days 1, 3, and 5 after OPCAB.

Elastin in asthma.

Extracellular matrix is generally increased in asthma, causing thickening of the airways which may either increase or decrease airway responsiveness, depending on the mechanical requirements of the deposited matrix. However, in vitro studies have shown that the altered extracellular matrix produced by asthmatic airway smooth muscle cells is able to induce increased proliferation of non-asthmatic smooth muscle cells, which is a process believed to contribute to airway hyper-responsiveness in asthma. Elastin is an extracellular matrix protein that is altered in asthmatic airways, but there has been no systematic investigation of the functional effect of these changes.