Cardioprotective Properties of Human Platelets Are Lost in Uncontrolled Diabetes Mellitus: A Study in Isolated Rat Hearts

Russo, Isabella; Femminò, Saveria; Barale, Cristina; Tullio, Francesca; Geuna, Stefano; Cavalot, Franco; Pagliaro, Pasquale; Penna, Cláudia

doi:10.3389/fphys.2018.00875

Cited by 19 publications

(27 citation statements)

References 74 publications

(119 reference statements)

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“…Interestingly, a recent study has shown that the infusion of platelets from healthy subjects in rat isolated hearts exerts cardioprotective effects by reducing infarct size [153] with a mechanism that depends on the platelet capacity to activate cardiac sphingosine-1-phosphate (S1P) receptors and extracellular signal-regulated kinase (ERK)/PI3K/protein kinase C (PKC) pathways. However, platelets from poorly controlled T2DM subjects, as mirrored by high values of glycated hemoglobin (HbA1c), lost their cardioprotective effects, released less S1P, and a positive correlation between infarct size and the amount of ROS produced by diabetic platelets was found [153].…”

Section: Atherothrombotic Diseasesmentioning

confidence: 99%

Influence of Cardiometabolic Risk Factors on Platelet Function

Barale

Russo

2020

IJMS

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Platelets are key players in the thrombotic processes. The alterations of platelet function due to the occurrence of metabolic disorders contribute to an increased trend to thrombus formation and arterial occlusion, thus playing a major role in the increased risk of atherothrombotic events in patients with cardiometabolic risk factors. Several lines of evidence strongly correlate metabolic disorders such as obesity, a classical condition of insulin resistance, dyslipidemia, and impaired glucose homeostasis with cardiovascular diseases. The presence of these clinical features together with hypertension and disturbed microhemorrheology are responsible for the prothrombotic tendency due, at least partially, to platelet hyperaggregability and hyperactivation. A number of clinical platelet markers are elevated in obese and type 2 diabetes (T2DM) patients, including the mean platelet volume, circulating levels of platelet microparticles, oxidation products, platelet-derived soluble P-selectin and CD40L, thus contributing to an intersection between obesity, inflammation, and thrombosis. In subjects with insulin resistance and T2DM some defects depend on a reduced sensitivity to mediators-such as nitric oxide and prostacyclin-playing a physiological role in the control of platelet aggregability. Furthermore, other alterations occur only in relation to hyperglycemia. In this review, the main cardiometabolic risk factors, all components of metabolic syndrome involved in the prothrombotic tendency, will be taken into account considering some of the mechanisms involved in the alterations of platelet function resulting in platelet hyperactivation.

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Section: Atherothrombotic Diseasesmentioning

confidence: 99%

Influence of Cardiometabolic Risk Factors on Platelet Function

Barale

Russo

2020

IJMS

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“…8 Pre-treatment of isolated rat hearts with platelets from healthy subjects was protective against IR injury, whereas platelets from diabetic subjects were not, possibly due to altered release of S1P. 27 Cardioprotective strategies such as IPC and IPost can induce the release of S1P. 25,26 Whether these manoeuvres affect S1P release from platelets is not clear.…”

Section: Plateletsmentioning

confidence: 99%

Circulating blood cells and extracellular vesicles in acute cardioprotection

Davidson

Andreadou

Barile

et al. 2018

Cardiovascular Research

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115

111

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During an ST-elevation myocardial infarction (STEMI), the myocardium undergoes a prolonged period of ischaemia. Reperfusion therapy is essential to minimize cardiac injury but can paradoxically cause further damage. Experimental procedures to limit ischaemia and reperfusion (IR) injury have tended to focus on the cardiomyocytes since they are crucial for cardiac function. However, there is increasing evidence that non-cardiomyocyte resident cells in the heart (as discussed in a separate review in this Spotlight series) as well as circulating cells and factors play important roles in this pathology. For example, erythrocytes, in addition to their main oxygen-ferrying role, can protect the heart from IR injury via the export of nitric oxide bioactivity. Platelets are well-known to be involved in haemostasis and thrombosis, but beyond these roles, they secrete numerous factors including sphingosine-1 phosphate (S1P), platelet activating factor, and cytokines that can all strongly influence the development of IR injury. This is particularly relevant given that most STEMI patients receive at least one type of platelet inhibitor. Moreover, there are large numbers of circulating vesicles in the blood, including microvesicles and exosomes, which can exert both beneficial and detrimental effects on IR injury. Some of these effects are mediated by the transfer of microRNA (miRNA) to the heart. Synthetic miRNA molecules may offer an alternative approach to limiting the response to IR injury. We discuss these and other circulating factors, focussing on potential therapeutic targets relevant to IR injury. Given the prevalence of comorbidities such as diabetes in the target patient population, their influence will also be discussed. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

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“…The evidence of increased COX‐1 expression in human diabetic patients is rather scarce. In one of the published studies, no differences were reported, while the other showed significantly higher expression in diabetic platelets . Animal models of disease are usually more homogenous in terms of confounding factors which influence intra‐population variation than patients, which is why the differences are easier to be detected.…”

Section: Discussionmentioning

confidence: 98%

Effects of three‐month streptozotocin‐induced diabetes in mice on blood platelet reactivity, COX‐1 expression and adhesion potential

Przygodzki

Kassassir

Talar

et al. 2019

Int J Experimental Path

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Diabetes is associated with an increased risk of cardiovascular disease. This is partially attributed to an altered activation status of blood platelets in this disease. Previously, alterations have been shown in COX-1 and protease activated receptor (PAR)-3 receptor expression in platelets in two animal models of diabetes, there have not been studies which address expression of these proteins in mice with long-term streptozotocin (STZ)-induced diabetes. We have also addressed the effect of diabetes on platelet adhesion under flow conditions. With the use of flow cytometry, we have shown that certain markers of platelet basal activation, such as active form of α IIb β 3 and of CD40L were increased in STZ-induced diabetic mice. Platelets from STZ-induced diabetic mice were also more reactive when stimulated with PAR-4 activating peptide as revealed by higher expression of active form of α IIb β 3 , membrane-bound on vWillebrand Factor and binding of exogenous fluorescein isothyanate-labelled fibrinogen.Expression of COX-1 and production of thromboxane A 2 in platelets of STZ-induced diabetic mice were higher than in control animals. We observed no effect of diabetes on ability of platelets to form stable adhesions with fibrinogen in flow conditions. We conclude that although certain similarities exist between patterns of activation of platelets in animal models of diabetes, the differences should also be taken into account. K E Y W O R D Scell adhesion, diabetes, platelets, prostanoids 42 | PRZYGODZKI et al.

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Cardioprotective Properties of Human Platelets Are Lost in Uncontrolled Diabetes Mellitus: A Study in Isolated Rat Hearts

Cited by 19 publications

References 74 publications

Influence of Cardiometabolic Risk Factors on Platelet Function

Influence of Cardiometabolic Risk Factors on Platelet Function

Circulating blood cells and extracellular vesicles in acute cardioprotection

Effects of three‐month streptozotocin‐induced diabetes in mice on blood platelet reactivity, COX‐1 expression and adhesion potential

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