Soluble P-Selectin and Proinflammatory Cytokines in Patients with Polygenic Type IIa Hypercholesterolemia

Ferroni, Patrizia; Basili, Stefania; Vieri, M; Martini, Francesca; Labbadia, Giancarlo; Bellomo, A; Gazzaniga, Pier Paolo; Cordova, C; Alessandri, C.

doi:10.1159/000022513

Cited by 25 publications

(31 citation statements)

References 34 publications

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“…Platelet activation in human subjects with elevated serum cholesterol levels is evident from the increased expression of P-selectin on platelets 25 and the corresponding increase in plasma levels of soluble P-selectin. 26 Mice maintained on a cholesterol-enriched diet exhibit P-selectin-dependent rolling and adhesion of platelets in postcapillary venules. 27 Platelet accumulation in atherosclerotic lesions is also well documented.…”

Section: Plateletsmentioning

confidence: 99%

Modulation of the Inflammatory Response in Cardiovascular Disease

2004

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Abstract-There is a growing body of evidence that inflammation might play an important role in the initiation and progression of cardiovascular diseases (CVDs). The designation of CVD as a chronic inflammatory process is further supported by evidence that the risk factors for CVD cause endothelial cells throughout the vascular tree to assume an inflammatory phenotype. These activated endothelial cells characteristically exhibit oxidative stress and increased adhesiveness for circulating leukocytes. Although initial efforts to define the mechanisms underlying the inflammatory phenotype in diseased endothelial cells have focused on the linkage between oxidative stress and adhesion molecule activation/expression, recent work has implicated a variety of additional factors that can modulate the magnitude and/or nature of the inflammatory responses in CVD. Platelets, angiotensin II, and the CD40/CD40 ligand signaling system are gaining recognition as contributors to the pathogenesis of CVD. These factors appear to converge with known pathways that link oxidative stress with adhesion molecule expression and help to explain the apparent integration of coagulation with inflammation in CVD. These factors also hold the promise of offering multiple sites for therapeutic intervention in CVD. Key Words: oxidative stress Ⅲ integrins Ⅲ angiotensin II Ⅲ adhesion molecules I nflammation is gaining widespread attention for its role in the initiation and progression of cardiovascular disease (CVD). Epidemiological studies have revealed strong associations between biochemical markers of systemic inflammation and both the presence of and future risk for symptomatic CVD. Animal experimentation as well as clinical studies has provided convincing evidence that the known risk factors for CVD (hypertension, diabetes, hypercholesterolemia, and smoking) can elicit both an inflammatory and a prothrombogenic phenotype in the vascular system. The phenotypic changes are more pronounced in endothelial cells and can include oxidative stress, increased expression of endothelial cell adhesion molecules (CAMs), activation of cell signaling pathways (eg, the CD40/CD40 ligand [CD40L] dyad), and the consequent adhesion and activation of leukocytes and platelets. In the microcirculation, the inflammatory manifestations of CVD are more readily visible in postcapillary venules. There is growing evidence, however, that the endothelium-dependent arteriolar dysfunction often associated with CVD is also linked to the systemic inflammatory response. [1][2][3][4] Because the expression of adhesion glycoproteins by activated endothelial cells is a rate-determining step in the recruitment of inflammatory cells, much attention has been devoted to the role of endothelial CAMs in CVD. This attention has produced considerable evidence for the: (1) altered endothelial CAM expression in animal models of CVD 2,5 ; (2) use of circulating levels of soluble endothelial CAMs (eg, soluble intercellular adhesion molecule-1 [sICAM-1]) as a marker for the severity of inflammati...

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Section: Plateletsmentioning

confidence: 99%

Modulation of the Inflammatory Response in Cardiovascular Disease

2004

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“…P-selectin is an adhesion molecule whose basal level is essentially endothelial cell-derived, 11 whereas its increase above the basal level is primarily attributable to platelet activation. 12 Because sP-selectin is enhanced in hypercholesterolemia, 3,5 it has been hypothesized that the platelet is the origin of this increment in this setting. 3,5 In our study, an endothelial origin of P-selectin is excluded by the fact that either simvastatin or aspirin did not reduce vWF levels.…”

Section: Discussionmentioning

confidence: 99%

“…12 Because sP-selectin is enhanced in hypercholesterolemia, 3,5 it has been hypothesized that the platelet is the origin of this increment in this setting. 3,5 In our study, an endothelial origin of P-selectin is excluded by the fact that either simvastatin or aspirin did not reduce vWF levels. Because P-selectin and vWF are coexpressed by endothelial cells, 13 one would expect a concomitant decrease of both proteins, provided that sP-selectin was derived from endothelial cells rather than platelets.…”

Section: Discussionmentioning

confidence: 99%

“…3 Enhanced thromboxane (Tx)-dependent platelet activation is present in hypercholesterolemic patients, as shown by increased urinary excretion of 11-dehydro-TxB 2 (a major enzymatic metabolite of TxA 2 ). 4 Besides this Tx-dependent pathway, other mechanisms may be involved in the occurrence of in vivo platelet activation in hypercholesterolemia, as suggested by the increased levels of soluble (s) P-selectin.…”

mentioning

confidence: 99%

“…4 Besides this Tx-dependent pathway, other mechanisms may be involved in the occurrence of in vivo platelet activation in hypercholesterolemia, as suggested by the increased levels of soluble (s) P-selectin. 3,5 A few years ago, platelets were thought to play a minor role, if any, in ongoing inflammation or vascular injury and repair beyond initial adhesion, secretion, and eicosanoid synthesis. However, increasing evidence is accumulating suggesting that platelets have inflammatory actions and are a rich source of chemokines (eg, platelet factor-4 and RAN-TES) 6,7 and inflammatory cytokines (eg, IL-1␤ and sCD40L) 8,9 that are preformed and packaged in storage granules.…”

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confidence: 99%

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Enhanced Interleukin-1β in Hypercholesterolemia

et al. 2003

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Background-This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1␤ levels in hypercholesterolemia. To this purpose, we compared the effects of a short-term treatment with simvastatin or low-dose aspirin on circulating levels of this cytokine. Methods and Results-Fifty patients with hypercholesterolemia were randomly allocated to receive an 8-week therapeutic course of simvastatin 20 mg daily (nϭ25) or aspirin 100 mg daily (nϭ25

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The adhesion molecule P-selectin and cardiovascular disease

Blann

Nadar

Lip

2003

European Heart Journal

461

385

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The adhesion molecule P-selectin (CD62P) is of interest because of its role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. Although present on the external cell surface of both activated endothelium and activated platelets, it now seems clear that most, if not all, of the measured plasma P-selectin is of platelet origin. P-selectin is partially responsible for the adhesion of certain leukocytes and platelets to the endothelium. Animal models have also shown the important role of P-selectin in the process of atherogenesis. For example, increased P-selectin expression has been demonstrated on active atherosclerotic plaques; in contrast, fibrotic inactive plaques lack P-selectin expression, and animals lacking P-selectin have a decreased tendency to form atherosclerotic plaques. Increased levels of soluble P-selectin in the plasma have also been demonstrated in a variety of cardiovascular disorders, including coronary artery disease, hypertension and atrial fibrillation, with some relationship to prognosis. The objective of this review is to provide an overview of the current literature on this molecule and thus present a concise view of its potential in dissecting the pathophysiology of atherosclerosis. In doing so we shall focus primarily on human biology but will note a small number of excellent lessons provided by non-human work.

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Soluble P-Selectin and Proinflammatory Cytokines in Patients with Polygenic Type IIa Hypercholesterolemia

Cited by 25 publications

References 34 publications

Modulation of the Inflammatory Response in Cardiovascular Disease

Modulation of the Inflammatory Response in Cardiovascular Disease

Enhanced Interleukin-1β in Hypercholesterolemia

The adhesion molecule P-selectin and cardiovascular disease

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