Abstract
Atherosclerosis affects many patients with type 2 diabetes. Both are associated with platelet activation, but it remains unclear how diabetes contributes to, or even enhances, platelet activation in patients with atherosclerosis. We therefore investigated the impact of diabetes on platelet activation and protease activated receptor-1 (PAR-1) mediated platelet response in patients with symptomatic coronary artery disease (CAD), as compared with other manifestations of atherosclerosis. Baseline P-selectin expression, thrombin receptor activating peptide-6 (TRAP-6) inducible P-selectin, and relative increase of platelet P-selectin after activation with TRAP-6 were measured using flow cytometry in platelets from 317 patients after angioplasty and stenting for symptomatic atherosclerotic disease, and from 50 healthy controls. Patients with symptomatic atherosclerosis exhibited significantly higher levels of baseline P-selectin expression, TRAP-6-inducible P-selectin and relative increase of platelet P-selectin after stimulation with TRAP-6 than healthy controls. Patients with symptomatic peripheral artery disease or cerebrovascular disease (PAD/CVD) had higher levels of platelet activation and PAR-1-mediated platelet reactivity than patients with symptomatic CAD. Of interest, CAD patients with diabetes responded more strongly to TRAP-6 than those without diabetes, and their platelet activation and PAR-1-mediated platelet reactivity resembled those from PAD/CVD patients. Compared with healthy controls, platelets from patients with symptomatic atherosclerotic disease are activated and susceptible to PAR-1-mediated activation. Diabetes affects platelet reactivity only in patients with symptomatic CAD, while other manifestations of atherosclerosis may have an overwhelming effect on platelet reactivity that is not further enhanced by diabetes.
Highlights
Patients with type 2 diabetes frequently suffer from atherosclerosis [1, 2], and it has been reported that diabetics have a two- to four-fold increased risk of coronary artery disease (CAD) and peripheral artery disease (PAD) [2,3,4], and a higher incidence of carotid plaques, than matched control populations [5]
It has been shown that improved metabolic control decreases platelet activation markers in patients with type 2 diabetes [23, 24]. These findings suggest, among others, a reduction in thrombin generation, which is abundant in obese type 2 diabetic patients [11]
Patients with PAD suffered from intermittent claudication (n = 165), patients with CVD had signs of transient cerebral ischaemia within 4 weeks before study enrolment (n = 37), and patients with CAD suffered from stable angina (n = 47) or acute coronary syndromes (ACS; n = 68) prior to percutaneous intervention
Summary
Patients with type 2 diabetes frequently suffer from atherosclerosis [1, 2], and it has been reported that diabetics have a two- to four-fold increased risk of coronary artery disease (CAD) and peripheral artery disease (PAD) [2,3,4], and a higher incidence of carotid plaques, than matched control populations [5]. Platelets play a central role in the development of thrombotic events in these patients, as they are activated in association with impaired metabolic control [9, 10], which itself promotes thrombin generation and vulnerability of atherosclerotic plaques [11, 12]. Thrombin activates platelets via protease-activated receptors (PARs) – PAR-1 and PAR-4
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