Relationship of Endothelial Microparticles to Obesity and Cardiovascular Disease Risk in Children and Adolescents

Abstract

Background Microparticles and endothelial microparticles (EMPs) are implicated in accelerating cardiovascular disease (CVD); however, data in pediatrics are limited. We examined the relationship of microparticles and EMPs with adiposity and subclinical CVD risk measures in a pediatric population to determine their potential as biomarkers of CVD risk. Methods and Results A cross‐sectional study of youth (n=280; ages 8–20 years) with a range of body mass index categories was used. Microparticles, EMPs, and activated EMPs were measured by flow cytometry. %Body fat and %visceral adipose tissue were measured by dual X‐ray absorptiometry. Measures of arterial stiffness and vascular wall structure were obtained. Linear regression (with log‐transformed outcomes) and logistic regression were used to evaluate associations and all results were exponentiated. Youth with overweight/obesity and severe obesity had 2.50 (95% CI, 1.56–4.01) and 3.42 (95% CI, 2.15–5.43) times the geometric means of the total number of microparticles, respectively, compared with those with normal weight. Youth with overweight/obesity and severe obesity had 1.97 (95% CI, 1.09–3.55) and 2.34 (95% CI, 1.31–4.19) times the geometric means of the total number of EMPs, respectively, compared with those with normal weight. There were positive associations between the levels of both microparticles and EMPs with higher adiposity measures and poor CVD risk measures. Youth with higher adiposity showed 1.84 times the odds of having high levels of activated EMPs (%) (odds ratio, 1.84; 95% CI, 1.08–3.14) compared with those with normal weight. Conclusions Levels of microparticles, EMPs, and activated EMPs were positively associated with adiposity and poor subclinical CVD risk in a pediatric population.

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…Thus, blocking the generation and release of EVs was found to reduce blood pressure in hypertensive rats [ 203 ]. Furthermore, an increase in circulatory EC-EV levels has been found in patients with endothelial dysfunction [ 204 ], obstructive sleep apnea [ 205 ], obesity [ 206 , 207 ], renal failure [ 208 ], coronary artery disease [ 209 ], myocardial infarction [ 210 , 211 , 212 ], β-thalassemia [ 213 ], and stroke [ 214 ]. Nevertheless, it is not clear if the increase in their number contributes to these conditions.…”

“…Similarly, in patients with inflammatory bowel disease, granulocyte-derived EVs enriched for metalloproteinases and pro-inflammatory cytokines have been shown to increase intestinal permeability [ 230 ]. Other studies have linked EV-mediated inflammation to CVDs [ 206 , 231 , 232 , 233 , 234 ], MS [ 189 , 235 , 236 , 237 ], and more. Autoimmune diseases can stem from EV-presenting self-antigens that auto-activate lymphocytes and trigger immune cells with antigen specificity for EVs’ own parent cells.…”

Endothelial dysfunction: molecular mechanisms and clinical implications

“…Acute‐phase proteins, cytokines (including IL‐6, IL‐1, and tumor necrosis factor‐alpha [TNF‐α]), adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), and endothelial microparticles (EMPs) have been extensively investigated as indicators of endothelial dysfunction. 5 , 6 , 7 Furthermore, interventions targeting endothelial dysfunction, such as traditional medicine, engineered extracellular vesicles (EVs), and molecular techniques, have shown promise in the prevention and mitigation of cardiovascular events and their complications. 8 , 9 , 10 Consequently, there is significant value in the exploration of novel biomarkers and therapeutic approaches for endothelial dysfunction.…”

Channels of Communication: Extracellular Vesicles in Environmental Stress and Human Disease

“… 14 In one study, rats exposed to tobacco smoke showed changes in blood EV biomarkers that were associated with lung function decline. 15 In another, smokers with preclinical loss of lung function had a higher circulating level of a type of EV called endothelial microparticles, known to be elevated in vascular-related disorders, 16 than did smokers with normal lung function. Both groups had more endothelial microparticles than healthy nonsmokers.…”