Microparticles from Patients with the Acute Coronary Syndrome Impair Vasodilatation by Inhibiting the Akt/eNOS-Hsp90 Signaling Pathway

Abstract

Objectives: Endothelial dysfunction is involved in the development of the acute coronary syndrome (ACS). Plasma microparticles (MPs) from other diseases have been demonstrated to initiate coagulation and endothelial dysfunction. However, whether MPs from ACS patients impair vasodilatation and endothelial function remains unclear. Methods: Patients (n = 62) with ACS and healthy controls (n = 30) were recruited for MP isolation. Rat thoracic aortas were incubated with MPs from ACS patients or healthy controls to determine the effects of MPs on endothelial-dependent vasodilatation, the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the interaction of eNOS with heat shock protein 90 (Hsp90), and nitric oxide (NO) and superoxide anion (O₂^-) production. The origin of MPs was assessed by flow cytometry. Results: MP concentrations were increased in patients with ACS compared with healthy controls. They were positively correlated with the degree of coronary artery stenosis. MPs from ACS patients impair endothelial-dependent vasodilatation, decrease both Akt and eNOS phosphorylation, decrease the interaction between eNOS and Hsp90, and decrease NO production but increase O₂^- generation in rat thoracic aortas. Endothelial-derived MPs and platelet-derived MPs made up nearly 75% of MPs. Conclusions: Our data indicate that MPs from ACS patients negatively affect endothelial-dependent vasodilatation via Akt/eNOS-Hsp90 pathways.

Microparticles: A Novel Player in Cardiovascular Diseases

“…Previously, it was demonstrated that MPs could reduce the generation of NO in cultured endothelial cells [9]. In the study by Han et al [8], the concentration of MPs was related to the stenosis of coronary arteries, in keeping with the previous observation by Biasucci et al [10], which showed a correlation between the concentrations of MPs and the severity of coronary artery disease. Interestingly, most of the circulating MPs in the ACS patients in their study were endothelial or platelet MPs; it has been suggested that these play the most important role in the pathogenesis of ACS.…”

“…In the context of mitral valve disease, in patients with atrial fibrillation compared to healthy volunteers, it has been found that an elevated endothelial MP concentration impairs endothelial function by inhibiting the Akt/eNOS-HSP90 signalling pathway [17]. This is in line with the results obtained by Han et al [8] in patients with ACS. Endothelial MPs have been also studied in heart failure.…”

“…In this issue of Cardiology , Han et al [8] have confirmed that MP concentrations are increased in ACS patients compared to in healthy subjects. They showed that these concentrations are positively correlated with the degree of coronary artery stenosis.…”

“…Accumulating evidence, including what appears in the study by Han et al [8], indicates that the endothelium plays a central role in the regulation of vascular homeostasis. A derangement of the endothelium can cause a shift from vasorelaxation to a vasocontrictive and prothrombotic state, which could, in turn, exacerbate plaque instability.…”

Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction

“…MPs, once they pinch off from the parent cell, can transfer the contents to the targeted cells and MPs from different origins or stimuli can lead to distinct phenotypic characteristics and functional effects [2]. Endothelial microparticles (EMPs) are released from the injured ECs and numerous studies have linked EMPs with many different vascular diseases, such as severe hypertension [3], acute coronary syndromes [4], acute lung injury [5]. During activation and apoptosis, endothelial cells release phenotypically and quantitatively distinct EMPs.…”