Eighteen patients had hemodynainically significant this website graft stenoses confirmed by imaging, and 18 were free from stenosis. The level of PMA in whole blood was quantified after blood draw using two-color flow cytometry. Three measurements were made per sample: the basal, in-vivo level of aggregates (baseline
PMA); the predisposition to spontaneously generate PMA (spontaneous PMA); and PMA generation by the addition of exogenous thrombin receptor-activating peptide (stimulated PMA). The baseline, in-vivo level of PMA was estimated by immediate flow analysis. The predisposition to spontaneously generate PMA was measured after in vitro incubation. Responsiveness to thrombin stimulation of the blood was quantified by the in vitro dose response to an exogenous thrombin receptor-activating peptide (sfllrn).
Results: Baseline PMA levels were similar in patients with vein graft stenosis vs nonstenosis (14.8% +/- 3.2 vs 10.1% +/- 1.5, respectively, mean +/- SEM). However, patients with stenosis showed higher spontaneous PMA levels (58.5% +/- 4.5 vs 28.3% +/- 4.3; P < .001) and higher stimulated PMA levels (P < .001; analysis of variance). Covariables of smoking, diabetes, statin, or antithrombotic therapy could not account for these differences.
Conclusions: Platelet-monocyte reactivity may play a role in the development of vein graft stenoses. Those
with/without stenosis differed primarily in their threshold, or predisposition to form aggregates (spontaneous PMA), while their basal circulating levels of PMA (baseline PMA) were similar. Silmitasertib These measurements may unmask pathologic differences in thrombo-inflammatory responsiveness that are not apparent in basal measurements. Understanding the causes and mechanisms leading to abnormal platelet-monocyte responses may improve approaches to predicting or preventing vein graft stenosis. (J Vase Surg 2011;54:1124-30.)
Clinical Relevance: Infrainguinal autogenous
vein grafts are especially prone to narrowing and failure with both inflammatory and thrombotic pathways implicated. Platelets MK-8776 manufacturer and monocytes are key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. Excessive platelet-monocyte interactions are associated with myocardial infarction, unstable coronary syndrome, and cerebral vascular accidents. This article bridges clinical and basic science. It has a potentially large clinical impact in that it could lead to development of methods that identify patients who have increased risk of graft failure and provide clues that help with the design of drugs that limit thrombo-inflammatory processes that lead to graft failure.