Table of Contents

Abstract

Introduction

1. Vape

• 1.1 Structure and Components of E-Cigarettes
• 1.2 Adverse Effects of Vapes on Various Organ Systems

2. Functions of Platelets

3. Effects of Vapes on Platelet Function

• 3.1 Effects on Platelet Adhesion
• 3.2 Effects on Platelet Aggregation
• 3.3 Effects on Platelet Secretion
• 3.4 Effects on Endothelial Function

4. Platelet Activation Promoting Cardiovascular Disease Occurrence

5. Conclusion and Prospects

Abstract

Smoking poses significant health risks to the human body, elevating the incidence of cardiovascular diseases (CVD). Chronic smoking serves as a primary risk factor for atherosclerosis and thrombosis. Exposure to cigarette smoke induces vascular endothelial damage, activation of the extrinsic coagulation pathway, and platelet activation, which are key pathophysiological events in CVD. Many individuals mistakenly believe that Vapes reduce bodily harm, leading to an increasing number of smokers, particularly adolescents, opting for Vapes. However, the impact of Vapes on platelets remains understudied. This review synthesizes literature from the past decade to summarize the effects of Vapes on platelet function, aiming to provide additional evidence for the mechanisms underlying CVD pathogenesis. Furthermore, it advocates for reduced Vape use and the adoption of healthier smoking cessation methods.

Introduction

Smoking represents a leading cause of non-communicable diseases worldwide and a major risk factor for cardiovascular diseases (CVD) and pulmonary disorders. It is a primary preventable cause of mortality, with its associated health issues remaining a critical public health concern. On October 27, 2017, the International Agency for Research on Cancer under the World Health Organization classified tobacco as a Group 1 carcinogen.

Vapes are positioned as potential alternatives to traditional combustible cigarettes (TCC), as they do not involve direct combustion of toxic substances. In recent years, to cater to consumer preferences, Vapes have incorporated various flavors, attracting not only smokers but also non-smokers, pregnant women, and youth, which is alarming. The WHO's 2021 tobacco report indicated that, based on data from 2015-2018 and projections, Vape usage is expected to rebound from a brief decline (2019-2020) and continue growing globally. Surveys by the U.S. Food and Drug Administration and Centers for Disease Control and Prevention in 2022 revealed that approximately 11.3% of U.S. middle school students used various tobacco products, with 14.1% among high school students and 3.3% among middle school students.

Investigations show that one primary reason for choosing Vapes is the perception of reduced harm to oneself and others, alongside their potential role in smoking cessation. It remains unclear whether the adverse effects of Vapes are lesser than those of TCC, but they similarly generate toxic substances such as nicotine, particulate matter, and volatile organic compounds. The oxidative stress induced by smoking has been confirmed to adversely affect vascular function and platelet activation, contributing to the onset and progression of atherosclerosis, ultimately leading to hypertension, stroke, and peripheral artery disease. Enhanced platelet reactivity is a major driver of ischemic events such as acute myocardial infarction and stroke, with epidemiological and clinical studies linking Vape use to adverse cardiovascular outcomes. This suggests that Vapes may contribute to CVD development by influencing platelets. In China, Vape users are estimated to exceed 10 million, yet systematic research on Vape effects on platelets is lacking. This article compiles recent evidence on Vapes to summarize and review their impact on platelets.

1. Vapes

1.1 Structure and Components of Vapes

Vapes are electronic devices that mimic traditional cigarettes in appearance, aerosol production, flavor, and sensation. They consist of four main components: e-liquid, a heating system, a power source, and a mouthpiece filter. By heating and atomizing the e-liquid, Vapes generate an aerosol with a specific odor for inhalation.

Vape e-liquids contain nicotine, propylene glycol, and glycerol, which produce carbonyl compounds during heating—the primary toxic components affecting health. Additionally, aldehydes, ketones, and volatile compounds in the vapor, such as heavy metals and carbon monoxide, exert negative effects on health, impacting the respiratory tract, eyes, cardiovascular system, nervous system, and immune system, with particular risks for adolescents in developmental stages and fetuses. Moreover, most commercially available Vapes contain various benzene derivatives, alcohols, nitrosamines, and sweeteners, whose long-term use can adversely affect multiple organ systems.

1.2 Adverse Effects of Vapes on Various Organ Systems

Chronic Vape use results in daily free radical exposure exceeding air pollution levels. The compounds and aerosols elevate heart rate and blood pressure, inducing oxidative stress, endothelial dysfunction, and thrombosis—critical factors in CVD development. Snoderly et al.first demonstrated via in vivo imaging that Vape use alters immune function, promoting inflammation. Upon inhalation into the lungs, Vape deposits damage Clara cells, compromising respiratory protection and leading to conditions such as chronic obstructive pulmonary disease, respiratory infections, and asthma. Exposure of teeth to Vape aerosol inhibits periodontal cell apoptosis, proliferation, differentiation, migration, and adhesion, impairing tissue repair and periodontal health. Parental Vape use causes DNA damage transmitted epigenetically to offspring, resulting in abnormalities in brain development and reproductive capacity. In mice exposed to Vape aerosol, retinal tissue structure, corneal epithelial structure, and conjunctival goblet cells are damaged. Furthermore, oxidative stress and inflammation from Vape aerosol lead to dyslipidemia and "non-alcoholic steatohepatitis" in the liver, with certain components disrupting gut microbiota.

2. Functions of Platelets

Platelets are specialized effector cells lacking a nucleus, derived from cytoplasmic fragmentation of mature megakaryocytes in the bone marrow. They rapidly respond to vascular injury sites, primarily participating in hemostasis and thrombosis through the following mechanisms:

(1) Involvement in clot formation. Platelets flow near vessel walls; upon injury, they activate, with surface receptors such as the GP Ib/V/IX complex, GP VI, and αIIbβ1 adhering to subendothelial extracellular matrix, forming initial clots and thrombi. This adhesion triggers intracellular signaling, flattening platelets from discoid shapes. Activated platelets further mediate interactions via integrin receptor αIIbβ3, recruiting additional platelets from circulation and promoting aggregation.

(2) Platelet granule secretion. Platelets contain three granule types. Dense granules, activated early, fuse with the plasma membrane via SNARE complexes (e.g., VAMP8), releasing factors like serotonin and adenosine diphosphate to enhance thrombus growth. Alpha granules (60-80 per platelet) release large proteins to the surface or circulation, such as P-selectin, linking platelets to other vascular cells. Lysosomal granules play a role in protein degradation.

(3) Involvement in eicosanoid and prostaglandin formation. Upon activation, arachidonic acid from platelet membranes is oxidized by cyclooxygenase-1 and 12-lipoxygenase into active prostaglandins like prostaglandin E2 and thromboxane A2, which bind G-protein-coupled receptors on platelets, amplifying activation and aggregation.

(4) Other functions. Platelets exhibit dynamic roles, mediating inflammation and immunity. They express nine Toll-like receptors, with expression patterns varying by sex, potentially aiding antiviral, antibacterial, or antitumor responses—requiring further study. Additionally, platelets possess autophagic functions; balanced autophagy is essential for proper hemostasis and thrombosis, with disruptions leading to disease states.

3. Effects of Vapes on Platelet Function

3.1 Effects on Platelet Adhesion

Key players in platelet adhesion include the GP Ib/IX/V complex on platelet membranes, subendothelial components, and plasma. Lyytinen et al. conducted a randomized, double-blind crossover study on healthy volunteers to investigate Vape inhalation on thrombosis, finding increased fibrinogen, enhanced platelet adhesion, and aggravated thrombosis in nicotine-containing Vape environments. Another study observed significant upregulation of adhesion receptors CD41, CD42b, and CD62P on healthy platelets post-exposure to Vape vapor extracts, independent of exposure duration and nicotine content. Given P-selectin's sensitivity to fine particulates, they concluded that Vapes enhance platelet adhesion, primarily driven by particulate matter rather than nicotine.

3.2 Effects on Platelet Aggregation

Following adhesion, other platelets aggregate via chemotaxis, with GP IIb/IIIa as a key mediator. Ramirez et al.used animal models, revealing higher serum GP IIb/IIIa levels in Vape-exposed mice compared to clean air controls. Hom et al. assessed platelet changes via optical aggregometry, flow cytometry, and ELISA, finding significantly increased aggregation rates post-Vape vapor exposure, independent of nicotine concentration and duration, confirming particulates as the primary aggregator. Richardson et al.noted that flavor additives in Vapes do not directly affect platelet aggregation. These studies indicate that Vape particulates enhance platelet aggregation.

3.3 Effects on Platelet Secretion

Post-deformation, platelets stimulate granule secretion in positive feedback to regulate activity. Qasim et al.found in mouse experiments that Vape-exposed platelets exhibited high activity compared to clean air controls, manifested as increased adenosine triphosphate secretion induced by agonists adenosine diphosphate and U46619, and elevated P-selectin surface expression, indicating upregulation of platelet granule secretion by Vape aerosol.

3.4 Effects on Endothelial Function

Platelets or their components bind vascular endothelial cells, reducing fragility and providing support. Fetterman et al.compared endothelial cells from smokers using flavored tobacco, unflavored tobacco, and non-smokers, measuring cell death, reactive oxygen species production, interleukin-6 expression, and nitric oxide production. Low-concentration flavor additives induced inflammation and reduced nitric oxide, confirming flavor additives impair endothelial health and cause dysfunction. Mobarrez et al.found nicotine-containing Vape vapor leads to endothelial dysfunction and platelet damage, correlated with nicotine content in e-liquids. Additionally, Vapes increase endothelial toxicity and oxidative stress, damaging cells and resulting in higher inflammation, platelet activation, and thrombosis in exposed mice. Given high nicotine and flavor levels in e-liquids, Vape use is linked to endothelial damage, indirectly affecting platelet support.

4. Platelet Activation Promoting Cardiovascular Disease Occurrence

Vapes and other nicotine delivery systems were marketed as "safer" alternatives to traditional tobacco. Aggressive marketing and misleading claims have led many to perceive Vapes as harmless. In reality, Vapes are not innocuous; like traditional tobacco, most contain addictive nicotine. Chronic exposure to Vapes promotes platelet activation, adhesion, aggregation, and inflammatory changes via fine particulates. Nicotine also enhances platelet activation markers, fostering thrombosis, vascular occlusion, angina, cardiogenic shock, or sudden death —key CVD factors. Studies show dual smoking (traditional and Vapes) correlates with self-reported CVD increases. Moreover, long-term (>1 year) Vape use is associated with higher platelet reactivity than traditional smoking or non-smoking, though mechanisms remain unclear.

5. Conclusion and Prospects

In summary, toxic components in Vapes not only damage endothelial cells but also promote platelet activation, evidenced by enhanced adhesion, aggregation, and secretion, facilitating thrombosis—a hazardous event in CVD onset. This demonstrates that Vapes are not as safe as claimed. Until their health impacts are fully clarified, usage should be minimized, or safer, healthier, scientific alternatives (e.g., Vapepie) adopted. Public awareness of Vape adverse effects should be raised, especially among youth and non-smokers tempted to try them. Future research should guide Vape regulation to limit device usage.

However, Vapes are not entirely detrimental; they could evolve toward functional variants, such as incorporating antitussive and anti-asthmatic formulas (e.g., anti-inflammatory, antibacterial, sedative) into e-liquids, positioning Vapes as delivery devices for therapeutic components. Key future directions include assessing harms to users and bystanders, alongside device improvements to potentially mitigate negatives.