Vascular
Young male smokers have altered platelets and endothelium that precedes atherosclerosis

https://doi.org/10.1016/S0022-4804(03)00343-3Get rights and content

Abstract

Background

Cigarette smoking results in abnormalities of platelets and endothelium with platelet dysfunction implicated in vascular complications. Healthy endothelium plays a pivotal role in regulating hemostasis via the inhibition of platelet activation and aggregation. Thus, we examined if platelet dysfunction correlated with serum vWF levels—a circulating marker of endothelial dysfunction.

Materials and methods

We tested this hypothesis in young male smokers. The parameters of platelet function tested included: CD62/CD63; Glycoprotein (GP) IIb/IIIa; Platelet function analzyer (PFA) studies, platelet aggregometry, flow assessment of platelet microparticles, platelet-leukocyte interactions and receptor numbers. Endothelial dysfunction was assessed with serum von Willebrand Factor (vWF).

Results

There was a significant increase in platelet CD62 receptor expression and aggregation with an associated delay in time to aggregation using PFA. Endothelial dysfunction was represented by higher serum levels of von Willebrand Factor. All other platelet parameters tested were within the standardized reference range.

Conclusions

These initial data suggests that anti-platelet therapy may have a role in reduction of platelet activation and aggregation in young smokers and possibly alter vascular endothelial abnormalities.

Introduction

Cigarette smoking is a major recognized risk factor for cardiovascular disease 1, 2 being associated with an increase in vascular morbidity and mortality such as myocardial infarction and sudden death. There exists strong evidence implicating enhanced platelet aggregation and activation 3, 4, 5 and dysfunctional vascular endothelium 6, 7.

Healthy endothelium is essential for the maintenance of hemostasis with endothelial derived nitric-oxide (NO) inhibiting platelet activation and aggregation 8, 9. Under physiological conditions platelets do not interact with the vascular endothelium. However, endothelial dysfunction or denudation and reduced bioavailability of NO and prostacyclin has been implicated in platelet activation and leads to enhanced platelet-endothelial interactions and arterial thrombosis [10].

When platelets aggregate they release thromboxane A, serotonin, and ADP. The latter two substances induce NO formation, which is vasodilatory and anti-aggregatory. All three substances are powerful vasoconstrictors when not counter-balanced by NO. Altered production or availability of endothelial NO is a key determinant in this dysfunction and predisposes to disease by facilitating platelet-endothelial interactions and allowing further monocyte/neutrophil adhesion to vascular endothelium.

Smokers with established macrovascular disease are reported to have platelet abnormalities. They display increased platelet reactivity and hypersensitivity to aggregating agents, predisposing to thrombus formation [11]. They lose sensitivity to the normal restraints exercised by prostacylins (PGI2) and NO generated by the vascular endothelium and this abnormal platelet physiology has been implicated in the vascular complications seen. This reactivity is characterized by increased glycoprotein (GP) IIb/IIIa (platelet fibrinogen receptor) complex, CD62/CD63 receptor and release of platelet microparticles [12].

Glycoprotein (GP) IIb/IIIa is a platelet specific integrin, which is a key mediator in platelet activation and aggregation to a variety of physiological and inflammatory stimuli. Blockage of this complex attenuates platelet aggregation and is now an important therapeutic target.

CD62/CD63 are proteins associated with α-granules of platelets. Upon platelet activation and granule secretion, the α-granule membrane fuses with the external plasma membrane and CD62/63 is expressed on the platelet surface [13].

Microparticles are shed from many cell types that undergo activation including platelets [14], monocytes [15], and endothelial cells and are used as platelet activation markers. They modulate interactions between circulating cells and the endothelium and may be of clinical relevance in the early stages of atherogenesis [16].

However, the majority of data pertains to smokers with established atherosclerosis and macrovascular disease 17, 18, 19. While dysfunctional endothelium in young smokers is known, the role of the platelet is not. The aims of this study, was to determine that platelet abnormalities are early alterations in young male smokers and that these correlate with serum vWF.

Section snippets

Subjects

Subjects were recruited from family and hospital staff members (Table 1). They were young male smokers (n = 10) of at least 10 cigarettes per day for 5 years. Exclusion criteria included diabetes, family history of premature heart disease, hypertension, and hypercholesterolemia. Control patients (n = 9) were a non-smoking, age and sex- matched group. All volunteers were requested to avoid aspirin and non-steroidal anti-inflammatory use for a 2-week period before assessment.

There were 40 ml of

Results

There were no significant differences between groups in terms of age, body mass index (BMI), blood pressure, pulse rate, total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol. All hematological parameters assessed were normal. These included coagulation times, hemoglobin, MCV, and hematocrit (Table 1). Factors known to affect closure times (platelet count, size, and volumes) were also normal (Table 1). There was no difference between groups in the number of platelet

Discussion

Platelets are paramount to the complex and dynamic process of vascular homeostasis through interaction with inflammatory mediators, vascular endothelium and various cytokine products. Their contribution to endothelial dysfunction in the smoker is crucial to atherogenesis and their importance in acute ischemic syndromes is supported by the clinical benefit of anti-platelet treatment with aspirin 22, 23.

However, there is a lack of clinical data relating to platelet characteristics and

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