Altered nitric oxide/cGMP platelet signaling pathway in platelets from patients with acute coronary syndromes

Bergandi, Loredana; Cordero, Marco; Anselmino, Matteo; Ferraro, Gaetana; Ravera, Laura; Dalmasso, Paola; Moiraghi, Corrado; Trevi, Gian Paolo; Ghigo, Dario; Bosìa, Amalia; Bergerone, Serena

doi:10.1007/s00392-010-0157-3

Cited by 15 publications

(6 citation statements)

References 32 publications

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“…Healthy donors showed no such increase, perhaps indicating that • NO generation was lower and that platelets were in a non-activated state compared to CHD. Such pre-activation has been noted previously in patients with CHD [44].…”

Section: Discussionsupporting

confidence: 82%

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Watt

Ewart

Greig

et al. 2012

Thrombosis Research

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BackgroundThe effect of reactive oxygen species (ROS) on platelet function in coronary heart disease (CHD) is complex and poorly defined. Platelet aggregation studies in healthy volunteers have demonstrated contrasting results when platelets are exposed to ROS. We investigated the effect of ROS on whole blood aggregation (WBA) and the endothelial cell-platelet interaction in patients with CHD.Methods and ResultsROS generated by xanthine and xanthine oxidase caused a concentration-dependent inhibition of WBA in blood from healthy donors and patients with CHD. In patients with CHD, 100 μM xanthine and 100 mU/ml xanthine oxidase inhibited WBA in response to 3 μg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p < 0.001) and in response to 5 μM ADP by 36.0% (95% CI 9.6%-62.4%, p = 0.005). Using nitrotyrosine expression, platelets isolated from patients with CHD were found to be susceptible to peroxynitrite damage. The addition of 1 × 105 cultured endothelial cells inhibited WBA in response to 3 μg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p < 0.05) and in response to 5 μM ADP by 31.6% (95% CI 2.5-60.7%, p < 0.05). Addition of xanthine and xanthine oxidase did not alter this effect, however pre-treatment of endothelial cells with a nitric oxide synthase inhibitor (L-NAME) partly reversed the inhibition.ConclusionROS inhibit WBA in blood from patients with CHD. Whilst endothelial cells also inhibit WBA, the effect is attenuated by L-NAME, suggesting that nitric oxide is likely to remain an important protective mechanism against thrombosis in CHD.

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Section: Discussionsupporting

confidence: 82%

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Watt

Ewart

Greig

et al. 2012

Thrombosis Research

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“…24 It has been hypothesized that increased inflammation leads to increased platelet activation in patients with ACSs. 25 To our knowledge, this is the first demonstration of an association between inflammatory markers and platelet activation as measured by PMP levels in a cohort of patients with ACSs who had moderate depressive symptoms. We hypothesize that neurohormones such as serotonin or brain-derived neurotrophic factor in individuals with depression may potentiate the platelet-activating properties of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 66%

Do Platelet-Derived Microparticles Play a Role in Depression, Inflammation, and Acute Coronary Syndrome?

et al. 2014

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Background Major depression is an independent predictor of increased mortality in patients presenting with acute coronary syndromes (ACS). There have been several mechanisms proposed to explain the link between depression and ischemic heart disease. Both abnormal platelet physiology and inflammation have been suggested as potential confounding variables. Objective We set out to examine platelet activation, inflammation, and levels of depression in hospitalized patients presenting with ACS. Methods We enrolled 28 patients with ACS and assessed levels of depression by PHQ-9. Platelet activation was assessed by the measurement of platelet microparticle levels and platelet aggregation to adenosine diphosphate and serotonin. Inflammatory markers were assessed by the measurement of TNF alpha, IL-6, and CRP. Results We found that ACS patients with moderate depressive symptoms who had higher TNF alpha, IL-6, and CRP levels had higher levels of platelet microparticles. We also found that ACS patients with PHQ-9 ≥ 10 had higher platelet aggregation to ADP. Conclusion Our results suggest that patients hospitalized for the treatment of an ACS who have moderate depression have increased platelet aggregation. These patients also have a positive association between elevated inflammatory markers and platelet activation, thus suggesting a pro-inflammatory component in ACS patients with depressive symptoms that may alter platelet function. These results are intriguing in that a potential pathway to explain the connection between depression, inflammation, and increased cardiovascular thrombosis might be found when both platelet activation and inflammation are measured.

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“…Both acute and chronic changes in plasma glucose correlate, indeed, with increased expression of platelet activation markers, such as P-selectin and CD40-ligand, on platelet surface [6,[49][50][51][52][53]. Hyperglycaemia may contribute to increase platelet activation via different mechanisms, which include augmented glycation of platelet surface proteins, which decreases membrane fluidity and increases platelet adhesion [54,55], and the direct osmotic effect of glucose [56], which can activate protein kinase C [57] and the nitric oxide/cyclic nucleotide pathway [58,59]. Further confirming these pieces of evidence, early intensive glucose control decreases platelet reactivity in patients with acute coronary syndrome and hyperglycaemia [60], and it reduces mortality in diabetic patients with acute coronary syndrome at 3.4 years of follow-up [61].…”

Section: Discussionmentioning

confidence: 99%

Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

Bosco

Vizio

Gruden

et al. 2021

IJMS

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Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.

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Altered nitric oxide/cGMP platelet signaling pathway in platelets from patients with acute coronary syndromes

Cited by 15 publications

References 32 publications

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Do Platelet-Derived Microparticles Play a Role in Depression, Inflammation, and Acute Coronary Syndrome?

Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

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