Early and Transient Release of Leukocyte Pentraxin 3 during Acute Myocardial Infarction

Abstract

Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet–neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin+ platelets causes the formation of neutrophil–platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte β2 integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.

Selective up‐regulation of the soluble pattern‐recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: Relevance for recent optic nerve ischemia

“…In those patients, kinetics were significantly faster than in the patients with GCA in the present study, since PTX3 levels peaked 7.5 hours after coronary care unit admission, were high at 24 hours, but were in the normal range in the following days (42). Forty-eight hours after acute myocardial infarction, PTX3 elevation is no longer detectable (18). Different sources may contribute to PTX3 synthesis in patients with GCA and acute myocardial infarction.…”

“…PTX3 synthesis is a hallmark of vascular injury (12). It occurs in atherosclerotic lesions (13)(14)(15)(16), as a response to acute mechanical damage of the vessel wall, such as that associated with coronary stenting (17), and during acute myocardial infarction (18,19). PTX3 inhibits neointimal thickening after balloon injury of rat carotid arteries via interference with fibroblast growth factor 2 (20,21).…”

Prognostic importance of Pentraxin 3 level in acute cholesistitis

“…[8] Besides this, platelet aggregation has been shown to be increased correlated with PTX3 released from neutrophils in acute coronary syndrome. [9] Diseases such as sepsis, myocardial infarction and rheumatoid arthritis have been shown to increase plasma PTX3 values. [8,10,11] These findings increase the usability of PTX3 elevation as a harbinger of a probably developing acute episode.…”

Increased pentraxin-3 level in patients with slow coronary flow

“…Furthermore, it is detected that PTX-3 is also produced at atherosclerotic plaque. Demonstration of correlated increase of PTX-3 secreted from neutrophils and platelet aggregation in acute coronary syndrome (20) may be one reason of increased platelet aggregation shown in patients with SCF (21). Level of PTX-3 was shown to increase in acute atherothrombosis in CAD, and was accepted as a predictor of mortality (20).…”