Dynamic Release and Clearance of Circulating Microparticles During Cardiac Stress

Abstract

Rationale: Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. Objective: To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. Methods and Results: We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Conclusions: Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Circulating Microparticles Decrease After Cardiac Stress in Patients With Significant Coronary Artery Stenosis

“…Whereas previous studies showed an increase of diverse circulating MPs in patients after DSE, 10,25 we found a drop of EMPs and MMPs in patients with relevant coronary stenosis and no changes in patients with stable CAD. These heterogenous findings regarding circulating MP (cMP) levels after stress might be due to (1) patient collectives that are not comparable, (2) variances in the used MP quantification protocols, and (3) relatively low patient numbers.…”

“…Surprisingly, this dynamic rise and fall was not apparent in patients with CAD that was predominantly diagnosed from medical history in this study and, when available, from QCA. 10 Augustine et al suggested that MPs may have a physiological function to remove stress-induced cellular byproducts and unwanted debris; and, therefore, a presumably physiological MP-level elevation in response to strenuous cardiac exercise can be observed in healthy subjects. 10 This response could be relevant to CVD pathogenesis because failure to clear MPs might lead to an increase in the circulating levels of proatherogenic factors.…”

“…10,11 This presumably physiological response was diminished in patients with coronary artery disease (CAD) undergoing DSE, as levels of circulating MP surprisingly remained unchanged after cardiac stress. 10 Coronary ischemia locally and systemically affects the function of endothelial cells, platelets, and monocytes, but its influence on circulating MP level is unknown. To explore circulating MPs as a tool for risk stratification in patients with stable CAD, we studied the kinetics of circulating MP levels during cardiac stress in patients with or without significant coronary artery stenoses.…”

Platelet Microvesicles (Microparticles) in Cardiac Surgery

“…Microvesicles released following dobutamine stress echocardiography are cleared from the circulation within an hour. 33 These studies suggest that microvesicles exert their actions in a very short time-frame and that there exists separate pathways for microvesicle and platelet clearance.…”

Cellular Biomarkers of Endothelial Damage Associated With Adverse Prognosis in Acute Coronary Events

“…При динамическом исследовании клиренса циркулирующих микрочастиц во время сердечно-го стресс-теста было показано, что их повышение в ответ на стресс может быть нормальной физио-логической реакцией [23]. Таким образом, остается не до конца ясна граница между физиологическим образованием и взаимодействием микрочастиц и началом их патологического влияния.…”