Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome

Pedicino, Daniela; Vinci, Ramona; Giglio, Ada Francesca; Pisano, Eugenia; Porto, Italo; Vergallo, Rocco; Russo, Giulio; Ruggio, Aureliano; d’Aiello, Alessia; Flego, Davide; Annibali, Gianmarco; Trotta, Francesco; Piacentini, Roberto; Niccoli, Giampaolo; Liuzzo, Giovanna; Crea, Filippo

doi:10.1016/j.jacc.2018.06.072

Cited by 62 publications

(43 citation statements)

References 41 publications

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“…17,22,23) Recent clinical study found that enhanced hyaluronidase 2 and CD44v6 splicing variant expression in circulating peripheral blood mononuclear cells was prevalent in ACS patients presenting with PE. 24) Intriguingly, based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we know that the predicted target genes of miR-3667-3p participate in the "proteoglycans in cancer" pathway. In addition, a positive correlation between circulating miR-3667-3p levels and fibrotic plaque constituent that mainly consists of collagen, proteoglycans, and SMCs has been observed in our study.…”

Section: Discussionmentioning

confidence: 99%

High Levels of Circulating MicroRNA-3667-3p Are Associated with Coronary Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction

Dong

Sun

et al. 2019

Int. Heart J.

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Plaque erosion (PE) is a significant substrate of acute coronary thrombosis. An improved ability to distinguish plaque phenotype in vivo among patients with ST-segment elevation myocardial infarction (STEMI) is of considerable interest because of the potential to formulate tailored treatment. This study assessed the plaque features and screened the circulating microRNAs (miRNAs) characteristically expressed in patients with PE compared with those with plaque rupture (PR). An miRNA microarray profile was generated in an initial cohort of eight STEMI patients with PE and eight clinically matched subjects with PR to select the circulating miRNAs with significant differences. miRNAs of interest were validated in a prospective cohort, and the plaque characteristics of enrolled patients were assessed by optical coherence tomography (OCT). Thirty culprit lesions were classified as PE (32.6%) and 46 as PR (50%). The main component of PE was fibrotic tissue, whereas the chief component of PR was lipids (P < 0.001). Thirty-four miRNAs were differentially expressed between the two groups; we validated five candidates and found that only the level of circulating miR-3667-3p exhibited significant discriminatory power in predicting the presence of PE (AUC = 0.767; P < 0.001). Our results show that high levels of circulating miR-3667-3p are closely related to PE in STEMI patients, which provides further evidence for PE pathophysiology and potential tailor treatment strategies.(Int Heart J 2019; 60: 1061-1069)

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Section: Discussionmentioning

confidence: 99%

High Levels of Circulating MicroRNA-3667-3p Are Associated with Coronary Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction

Dong

Sun

et al. 2019

Int. Heart J.

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“…The sub-endothelial matrix of eroded plaques contains abundant hyaluronan and its binding partner versican [5]. The recent observation that OCT-defined plaque erosion patients have increased HYAL2 (the enzyme responsible for degrading high-molecular-weight hyaluronan to its proinflammatory 20-kDa isoform) and the hyaluronan receptor CD44v6 adds weight to a potential causal relationship [9]. Hyaluronan and versican may regulate vascular inflammation in atherosclerosis [75,76].…”

Section: Discussionmentioning

confidence: 99%

“…For example, plaque rupture occurs on inflamed and lipid-rich plaques with a greater degree of calcification. In contrast, sites of erosion generally occur on smooth muscle cell-and proteoglycan-rich plaques, specifically containing high levels of versican and the glycosaminoglycan hyaluronan and low levels of biglycan, containing few inflammatory leucocytes [1,[5][6][7][8][9]. In addition, the thrombi overlying eroded plaques display more organisation, indicative of a longer existence, potentially up to 7 days before presentation of clinical symptoms [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

Satta

McElroy

Langford-Smith

et al. 2019

Preprint

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Endothelial erosion of atherosclerotic plaques and resulting thrombosis causes approximately 30% of acute coronary syndromes (ACS). As changes in the haemodynamic environment strongly influence endothelial function and contribute to plaque development, we reconstructed the coronary artery geometries of plaques with thrombi overlying intact fibrous caps from 17 ACS patients and performed computational fluid dynamic analysis. The results demonstrated that erosions frequently occur within areas of stenosis exposed to elevated flow. We recapitulated this flow environment in vitro, exposing human coronary artery endothelial cells to elevated flow and modelled smoking (a risk factor for erosion) by exposure to a combination of aqueous cigarette smoke extract and TNFα. This treatment induced endothelial detachment, which increased with pharmacological activation of the antioxidant system controlled by transcription factor Nrf2 (encoded by NFE2L2). The expression of Oxidative Stress Growth INhibitor genes OSGIN1 and OSGIN2 increased under these conditions and also in the aortas of mice exposed to cigarette smoke. Sustained high level expression of OSGIN1+2 resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and dysregulation of autophagy. Overexpression of either Nrf2 or OSGIN1+2 induced cell detachment, which did not depend on apoptosis, and could be partially rescued by inhibition of HSP70 using VER-155008, or AMP kinase activation using metformin. These findings demonstrate that under elevated flow, smokinginduced hyperactivation of Nrf2 can trigger endothelial cell detachment, highlighting a novel mechanism that could contribute to ACS involving endothelial erosion overlying stenotic plaques.

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“…6 Furthermore, an in vivo experiment found that hyaluronidase 2 (HYAL2) and its receptor mediated the recruitment of polymorphonuclear (PMNc) leukocytes and the formation of thrombi in plaque erosion was induced by ow perturbation. 7 However, whether systemic HA changes in STEMI is unknown. Moreover, the difference in circulating HA expression between plaque rupture and erosion has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

The association between plasma hyaluronan level and plaque types in ST-Segment–Elevation Myocardial Infarction patients

Tan

Sheng

et al. 2020

Preprint

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Background The metabolism of hyaluronan (HA) is widely known to be involved in the process of acute coronary syndrome, but it is unknown how circulating HA levels change in ST-Segment–Elevation Myocardial Infarction (STEMI) patients and whether HA is associated with plaque morphology, including rupture and erosion. Objectives This study focused on the changes in the plasma levels of HA and CD44 in STEMI patients and their relationship with plaque morphology evaluated by optical coherence tomography (OCT). Methods We prospectively enrolled 3 cohorts in this study, including 162 patients with STEMI, 34 patients with stable coronary artery disease (SCAD) and 50 healthy controls. Plaque morphology was detected by OCT analysis, and the plasma levels of HA and CD44 were examined by enzyme-linked immunosorbent assay (ELISA). We compared HA and CD44 expression among STEMI patients, SCAD patients and healthy controls, as well as in plaque rupture and plaque erosion. Results The plasma levels of HA and CD44 were significantly lower in STEMI patients than in healthy controls (p = 0.009 and p < 0.001, respectively). In addition, plasma HA expression in plaque erosion was significantly lower than that in plaque rupture (p = 0.021), whereas no differences were found in soluble CD44 expression between plaque rupture and erosion. Conclusions Low levels of circulating HA and CD44 were independently correlated with STEMI, and low levels of HA were associated with plaque erosion compared with rupture. Moreover, plasma HA might be a useful biomarker for identifying plaque erosion to improve the risk stratification and management of STEMI patients.

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Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome

Abstract: HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.

Cited by 62 publications

References 41 publications

High Levels of Circulating MicroRNA-3667-3p Are Associated with Coronary Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction

High Levels of Circulating MicroRNA-3667-3p Are Associated with Coronary Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction

A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

The association between plasma hyaluronan level and plaque types in ST-Segment–Elevation Myocardial Infarction patients

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