IntroductionPlatelet activation is thought to be a key event in acute vascular thrombosis. Therefore, prevention of enhanced platelet activation is a major target of therapeutic strategies fighting cardiovascular and cerebrovascular diseases. [1][2][3] An important stimulus for physiologic platelet activation and thrombus formation is the contact of platelets with components of the subendothelial matrix, like collagen. 4 Although Marcus et al have shown as early as 1977 that platelets have the ability to release superoxide anions (O 2 Ϫ ), 5 it was only recently proposed that platelets stimulated by collagen produce reactive oxygen species (ROS) such as hydrogen peroxide, 6 hydroxyl radicals, 7 or O 2 Ϫ . 7,8 While O 2 Ϫ , a highly reactive radical, damages cells in high concentrations by reacting with proteins, lipids, and DNA, in low concentrations its continuous production, with similarity to second messengers, has been suggested to indirectly affect signal transduction processes. 9,10 Platelet agonists other than collagen, such as thrombin or ADP, do not seem to induce ROS formation during aggregation. 8 This difference raises the question whether O 2 Ϫ formation could serve a modulating function when thrombus formation is induced by collagen.The cellular source of platelet O 2 Ϫ is unclear. Growing evidence supports the assumption that platelet activation by collagen is specifically due to binding to the glycoprotein VI (GPVI)-receptor, 11,12 resulting in a cascade of tyrosine phosphorylation events ultimately leading to activation of phospholipase C␥ (PLC␥), 13 which is known to strongly activate protein kinase C (PKC) through production of diacylglycerol. 4 Recently, evidence for the existence of a neutrophil-type reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase in platelets that can be activated by PKC and is involved in O 2 Ϫ formation has been presented, [14][15][16] similar as in other O 2 Ϫ -generating systems, like the vascular endothelium. In endothelial cells, an NAD(P)H oxidase is the main source of O 2 Ϫ . 17 As O 2 Ϫ readily reacts with NO, this has been suggested to result in attenuated 18,19 and the role of O 2 Ϫ in the regulation of vascular tone has become a major focus of interest. 17 Moreover, antioxidants like N-acetylcysteine (NAC) have been shown to exert direct antiaggregatory effects. 20 Although these findings raise the possibility that platelet-derived O 2 Ϫ is involved in regulating platelet activation, evidence for a role of platelet-derived O 2 Ϫ in platelet function is rare. In a canine model of coronary arterial thrombosis, thrombus formation was regulated by intraplatelet redox state. 21 Leo and colleagues have shown that platelets subjected to anoxia/ reoxygenation are more reactive, due to an enhanced O 2 Ϫ generation. 14 However, so far it remains unclear whether an enhanced O 2 Ϫ production occurs also during direct platelet activation, such as with collagen, and how this could affect thrombus growth. Whereas Supported by a grant from the Friedrich-...

In contrast to earlier studies that compared CMRI with morphological examination (CA) alone, the present study compared CMRI with CA plus a standard invasive functional assessment (FFR) and demonstrated that CMRI is able to distinguish haemodynamically relevant from non-relevant coronary lesions with a high sensitivity and specificity and may therefore contribute to clinical decision-making.

DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.

No abstract

Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.