Inflammation and thrombosis – testing the hypothesis with anti- inflammatory drug trials

Abstract

SummaryThe hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammationrelated plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.

Morroniside on anti-inflammation activities in rats following acute myocardial infarction

“…Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1β. The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) examines how blocking IL-1β with canakinumab lowers recurrence rates of myocardial infarction, stroke and cardiovascular disease [ 24 25 ].…”

Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis

“…n tested % positive n tested % positive disease, shares many of the aforementioned features with infection and may also contribute to thrombosis. 16 PVT induced by inflammation or infection can be seen close to the site of infection/inflammation and may extend and or embolise to the portal trunk and branches ( Fig. 1).…”

Procoagulant activity during viral infections

“…Thrombin generation during inflammation shifts the system towards the procoagulant state (1, 28). Also, protease-activated receptors (PARs) activation on the ECs induces the TF expression, von Willebrand factor, and other pro-inflammatory cytokines release during systemic inflammation (29)(30)(31).…”