Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker

Abstract

Early recognition of vulnerable carotid plaques could help in identifying patients at high stroke risk, who may benefit from earlier revascularisation. Nowadays, different biomarkers of plaque instability have been unravelled, among these miRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression. The goal of the present study was to determine whether miR-200c could be an atherosclerosis biomarker. Carotid plaques of patients that underwent carotid endarterectomy (CEA) were assayed for miR-200c expression. miR-200c was up-regulated in carotid plaques (n=22) and its expression was higher in unstable (n=12) compared with stable (n=10) plaques. miR-200c positively correlated with instability biomarkers (i.e. monocyte chemoattractant protein-1, cicloxigenase-2 (COX2), interleukin 6 (IL6), metalloproteinase (MMP) 1 (MMP1), 9 (MMP9)) and miR-33a/b. Moreover, miR-200c negatively correlated with stability biomarkers (i.e. zinc finger E-box binding homoeobox 1 (ZEB1), endothelial nitric oxide (NO) synthase (eNOS), forkhead boxO1 (FOXO1) and Sirtuin1 (SIRT1)) (stable plaques = 15, unstable plaques = 15). Circulating miR-200c was up-regulated before CEA in 24 patients, correlated with miR-33a/b and decreased 1 day after CEA. Interestingly, 1 month after CEA, circulating miR-200c is low in patients with stable plaques (n=11) and increased to control levels, in patients with unstable plaques (n=13). Further studies are needed to establish whether miR-200c represents a circulating biomarker of plaque instability. Our results show that miR-200c is an atherosclerotic plaque progression biomarker and suggest that it may be clinically useful to identify patients at high embolic risk.

The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk

“…Further, circulating miR-200c correlates with cardiac hypertrophy and diastolic dysfunction as assessed by E/e ′ and miR-200a with cardiac hypertrophy and arterial stiffness. In light of the findings of the present work and of the previously described negative effects of miR-200c and miR-200a on endothelial [24,25,29,63] and vascular smooth muscle cells [31] and cardiac [45][46][47] function, the upregulation of these miRNAs could play a role in the inflammation and oxidative stress upregulation, increasing the risk of adverse CV events in psoriatic patients.…”

“…Recently, we found that miR-200c is upregulated in carotid plaques and its expression is higher in unstable vs. stable plaque, its expression levels correlated with inflammatory markers, and circulating miR-200c levels were highly upregulated in the plasma of atherosclerotic patients compared to healthy subjects [29].…”

“…Since miR-200c has a role in endothelial dysfunction [25] and increases in both plaques and plasma of atherosclerotic patients [29], we evaluated whether miR-200c expression levels may relate to echocardiographic findings associated with an increased CV risk. To this aim, we correlated circulating miR-200c levels with some echocardiographic parameters (see Table 2) assessed both in Pso patients (N = 17) and in Ctrl patients (N = 23).…”

“…miR-200c increases also in carotid plaques, and its expression is higher in unstable vs. stable plaques and is upregulated in the plasma of atherosclerotic patients. Further, miR-200c expression displays a positive correlation with the inflammatory molecules interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2) and also with plaque destabilizators, such as metalloproteinase-(MMP-) 1 and MMP-9 [29].…”

UTMD inhibit EMT of breast cancer through the ROS/miR-200c/ZEB1 axis

“…The results revealed that US and UTMD both showed the potential in upregulation of miR-200c. The levels of miR-200c in MDA231 cells of UTMD group were higher than those of control and US groups, which was similar to the findings in previous studies on the relationship of oxidative stress and miR-200c 27,28 . MiR-200c has been identified to play a central role in cancer aggressiveness by controlling tumor spreading and drug resistance through a double negative-feedback loop with the transcription factor ZEB1 [5][6][7]29 .…”