The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4

Abstract

The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals ( n = 343 ) were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants ( P < 0.001 ). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells ( P < 0.001 ). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells ( P < 0.001 ). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels ( P < 0.001 ). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.

Effect of miR-21 in mesenchymal stem cells-derived extracellular vesicles behavior

“…Several authors already indicated the role of miR-21 as an inflammation marker in age-associated diseases [20,21] which was characterized by a prominent activation of the innate immune response. Besides elevated circulatory miR-21 concentrations have a positive correlation with aging [2]. Our group have reported that miR-21 was abundant in extracellular vesicles from aging-MSC and after conducting functional experiments inhibiting its expression, it was demonstrated the link between miR-21 expression and damage-associated molecular patterns and SASP by aging [9].…”

Evaluation of New Cardiac Damage Biomarkers in Polytrauma: GDF-15, HFABP and uPAR for Predicting Patient Outcomes

“…In a rat model of drug-induced cardiac injury, miR-21 was specifically localized to inflammatory cell infiltrates in the heart and therefore was suggested as a biomarker of cardiotoxicity [47]. In patients with coronary heart disease, expression of plasma miR-21 was found to be progressively higher in single-, dual-, and multivessel occluded coronary artery disease patients [14]. In heart failure patients, the level of plasma miR-21 was higher than in healthy controls, but no association between this miRNA and the prognostic outcome parameters was described [48].…”

“…In patients with coronary artery disease, the expression of miR-21 in plasma samples progressively increased in those with single-, dual-and multivessel occlusion. This suggests the potential diagnostic capability of miRNAs for cardiac damage [14]. Furthermore, multiple studies have focused on the identification of biomarker miRNAs in small extracellular vesicles (EVs) or exosomes in recent years.…”

PDCD4 Inhibition Alleviates Neuropathic Pain by regulating Spinal Autophagy and neuroinflammation

“…As a cancer-inhibiting protein, PDCD4 is involved in the occurrence and development of tumors [10] . Recent years, numerous studies have reported the role of PDCD4 in other diseases such as polycystic ovary syndrome, obesity, diabetes, and coronary artery atherosclerosis [11][12][13][14] . PDCD4 also plays a crucial regulatory role in in ammation [15] .…”