Alterations in Platelet Function During Aging: Clinical Correlations with Thromboinflammatory Disease in Older Adults

Mohebali, Donya; Kaplan, David; Carlisle, McKenzie; Supiano, Mark A.; Rondina, Matthew T.

doi:10.1111/jgs.12700

Cited by 62 publications

(47 citation statements)

References 55 publications

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“…Previous studies investigated the interplay between platelet activation and aging using ex vivo methods to assess platelet function, such as beta-thromboglobulin and platelet factor 4 [5]. Despite a relationship between platelet activation and aging emerged from previous studies, small sample size, lack of follow-up and, overall unreliability, of ex vivo tests assessing platelet activation limits definite conclusion.…”

Section: Discussionmentioning

confidence: 99%

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Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

et al. 2016

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Aging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, ≥ 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70-79 (p < 0.001) and ≥ 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF.

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Section: Discussionmentioning

confidence: 99%

“…These trials demonstrated, a significant reduction of CVEs in patients treated with aspirin [2, 3]. While experimental studies demonstrated a relationship between platelet activation and aging in animals [4], data in humans are inconclusive because of unreliable methods to assess platelet activation or small sample size [5–7]. …”

Section: Introductionmentioning

confidence: 99%

Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

et al. 2016

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“…57 The dual function of 2-AG should be taken into account, especially considering that platelet hyperactivation is related to aging, inflammation and cancer. 58,59 Age-related decline in cardiovascular function (and, therefore, susceptibility to thrombotic and inflammatory disorders) is often associated to increased levels of reactive oxygen species and oxidative stress; 60,61 since aged platelets display increased NADPH oxidase expression and hydrogen peroxide generation, platelet hyperactivity may contribute to this phenomenon. 62 Aging and activated platelets also modulate lineage-specific development, as well as the senescence program itself, thus promoting cell transformation and playing a role in the early progression to malignancy; [63][64][65][66] in particular, by shedding micro-RNA-containing microvesicles, activated platelets may have clinical relevance in promoting tumor growth and spread, 67 and potentially could be used as biomarkers, as circulating micro-RNA-containing microvesicles may differ according to cancer stage.…”

Section: Discussionmentioning

confidence: 99%

2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts

et al. 2014

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Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors toward the megakaryocytic lineage. Against this background, we sought to further interrogate the role of 2-AG in megakaryocyte/platelet physiology by investigating terminal differentiation, and subsequent thrombopoiesis. To this end, we used MEG-01 cells, a human megakaryoblastic cell line able to produce in vitro platelet-like particles.2-AG increased the number of cells showing ruffled surface and enhanced surface expression of specific megakaryocyte/platelet surface antigens, typical hallmarks of terminal megakaryocytic differentiation and platelet production. Changes in cytoskeleton modeling also occurred in differentiated megakaryocytes and blebbing platelets. 2-AG acted by binding to CB 1 and CB 2 receptors, because specific antagonists reverted its effect. Platelets were split off from megakaryocytes and were functional: they contained the platelet-specific surface markers CD61 and CD49, whose levels increased following stimulation with a natural agonist like collagen. Given the importance of 2-AG for driving megakaryopoiesis and thrombopoiesis, not surprisingly we found that its hydrolytic enzymes were tightly controlled by classical inducers of megakaryocyte differentiation.In conclusion 2-AG, by triggering megakaryocyte maturation and platelet release, may have clinical efficacy to counteract thrombocytopenia-related diseases.

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“…Secondary hemostasis corresponds to the activation of coagulation factors and the formation of the fibrin network. Meanwhile fibrinolysis is a mechanism of fibrin breakdown for blood clotting to occur [23,24].…”

Section: Introductionmentioning

confidence: 99%