Platelet hyaluronidase 2 enrichment in acute coronary syndromes: a conceivable role in monocyte-platelet aggregate formation

Vinci, Ramona; Pedicino, Daniela; d’Aiello, Alessia; Ciampi, Pellegrino; Ponzo, Myriana; Bonanni, Alice; Russo, Giulio; Montone, Rocco Antonio; Massetti, Massimo; Crea, Filippo; Liuzzo, Giovanna

doi:10.1080/14756366.2021.1900159

Cited by 8 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences in innate and adaptive immune system have been described in ACS patients (Liuzzo et al, 2007(Liuzzo et al, , 2020Flego et al, 2016;Leers et al, 2017;Pedicino et al, 2018a;Leistner et al, 2020). Starting from PBMCs as source material, our group documented an altered hyaluronan metabolism in NSTE-ACS patients presenting with plaque erosion (Pedicino et al, 2018b), further confirmed by later investigations on platelets and monocyte-platelet interaction (Vinci et al, 2021). Those findings pointed the attention to the extracellular matrix derangement and its altered components (Angelini et al, 2018).…”

Section: Discussionsupporting

confidence: 64%

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture

Vinci

Pedicino

Bonanni

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

The evaluation of monocyte subset distribution among acute coronary syndrome (ACS) patients according to culprit coronary plaque morphology has never been explored. We evaluated whether there were significant differences in frequency of circulating monocyte subsets isolated from ACS patients according to optical coherence tomography (OCT) investigation of plaque erosion and rupture. We enrolled 74 patients with non-ST-elevation ACS (NSTE-ACS), 21 of them underwent OCT investigation of the culprit coronary plaque and local macrophage infiltration (MØI) assessment. As control, we enrolled 30 chronic coronary syndrome (CCS) patients. We assessed the frequency of monocyte subsets in the whole study population, in reliance on their CD14 and CD16 expression (classical, CM: CD14++CD16–; intermediates, IM: CD14++CD16+; non-classical, NCM: CD14+CD16++). Then, we tested the effect of lipopolysaccharide (LPS) (a CD14 ligand) on peripheral blood mononuclear cells (PBMCs) of NSTE-ACS patients, quantifying the inflammatory cytokine levels in cell-culture supernatants. Our data proved that monocyte subsets isolated from NSTE-ACS patients represent a peculiar biological signature of the pathophysiological mechanism lying beneath atherosclerotic plaque with a ruptured fibrous cap (RFC) as compared with plaque erosion. Moreover, the magnitude of LPS-mediated effects on IL-1β, IL-6, and IL-10 cytokine release in cell-culture supernatants appeared to be greater in NSTE-ACS patients with RFC. Finally, we described a fourth monocyte population never explored before in this clinical setting (pre-classical monocytes, PCM: CD14+CD16–) that was prevalent in NSTE-ACS patients as compared with CCS and, especially, in patients with RFC and culprit plaque with MØI.

show abstract

Section: Discussionsupporting

confidence: 64%

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture

Vinci

Pedicino

Bonanni

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…HYAL2 (hyaluronidase 2) is related to inflammatory responses and cardiometabolic pathology. Expression of HYAL2 has been linked to acute coronary syndromes (Vinci et al, 2021) and inflammatory cytokines, chemokines, and angiogenic factors in bladder cancer tissue (Dominguez‐Gutierrez et al, 2021). KCNJ16 ( potassium inwardly rectifying channel subfamily J member 16) is important for potassium transport into kidney cells and has been associated with metabolic acidosis (Webb et al, 2021) as well as hypotension, hypokalemia, and associated mortality in rats fed a high salt diet (Palygin et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Section: Inflammation Immune Function and Accelerated Agingmentioning

confidence: 99%

PTSD, major depression, and advanced transcriptomic age in brain tissue

Zhao

Logue

Hawn

et al. 2022

Depression and Anxiety

View full text Add to dashboard Cite

Background: Psychiatric disorders have been associated with advanced epigenetic age in DNA methylation, yet this relationship has not been studied in the brain transcriptome. We examined transcriptomic age using an RNA-based algorithm recently developed by Ren and Kuan ("RNAAgeCalc") and the associations between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and alcohol use disorder with age-adjusted RNA age ("RNA age residuals") in three brain regions: dorsolateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), and motor cortex.Methods: RNA sequencing was used to measure gene expression in postmortem brain tissue from the VA National PTSD Brain Bank (n = 94; 59% male).Results: Linear models revealed that diagnoses of PTSD and/or MDD were positively associated with RNA age residuals in vmPFC only (p-adj = 0.012). Three genes in the RNAAgeCalc algorithm (KCNJ16, HYAL2, and CEBPB) were also differentially expressed in association with PTSD/MDD in vmPFC (p-adj = 6.45E−05 to 0.02). Enrichment analysis revealed that inflammatory and immune-related pathways were overrepresented (p-adj < 0.05) among the 43 genes in RNAAgeCalc that were also at least nominally associated with PTSD/MDD in vmPFC relative to the 448 RNAAgeCalc genes. Endothelial and mural cells were negatively associated with RNA age residuals in vmPFC (both p-adj = 0.028) and with PTSD/MDD (both p-adj = 0.017).Conclusions: Results highlight the importance of inflammation and immune system dysregulation in the link between psychopathology and accelerated cellular aging and raise the possibility that blood−brain barrier degradation may play an important role in stress-related accelerated brain aging.

show abstract

“…Notably, only one gene of our array, HYAL2, originally involved in hyaluronan catabolism and glycocalyx impairment [ 27 , 28 , 29 ], displayed an increased expression in PBMCs of INOCA patients. HYAL2 has been studied in the context of shear stress and plaque erosion [ 27 , 30 , 31 ]; however, no study before has investigated HYAL2 in INOCA patients. The endothelium bears a crucial aspect in vascular tone modulation.…”

Section: Discussionmentioning

confidence: 99%

Molecular Hallmarks of Ischemia with Non-Obstructive Coronary Arteries: The “INOCA versus Obstructive CCS” Challenge

Bonanni

d’Aiello

Pedicino

et al. 2022

JCM

Self Cite

View full text Add to dashboard Cite

Up to 4 million patients with signs of myocardial ischemia have no obstructive coronary artery disease (CAD). The absence of precise guidelines for diagnosis and treatment in non-obstructive CAD encourages the scientific community to fill the gap knowledge, to provide non-invasive and less expensive diagnostic tools. The aim of our study was to explore the biological profile of Ischemia with Non-Obstructive Coronary Arteries (INOCA) patients with microvascular dysfunction compared to patients presenting with obstructive chronic coronary syndrome (ObCCS) in order to find specific hallmarks of each clinical condition. We performed a gene expression array from peripheral blood mononuclear cells (PBMCs) isolated from INOCA (n = 18) and ObCCS (n = 20) patients. Our results showed a significantly reduced gene expression of molecules involved in cell adhesion, signaling, vascular motion, and inflammation in INOCA as compared to the ObCCS group. In detail, we found lower expression of Platelet and Endothelial Cell Adhesion Molecule 1 (CD31, p < 0.0001), Intercellular Adhesion Molecule-1 (ICAM1, p = 0.0004), Tumor Necrosis Factor (TNF p = 0.0003), Transferrin Receptor (TFRC, p = 0.002), and Vascular Endothelial Growth Factor A (VEGFA, p = 0.0006) in the INOCA group compared with ObCCS. Meanwhile, we observed an increased expression of Hyaluronidase (HYAL2, p < 0.0001) in INOCA patients in comparison to ObCCS. The distinct expression of molecular biomarkers might allow an early and non-invasive differential diagnosis between ObCCS and INOCA, improving clinical management and treatment options, in the era of personalized medicine.

show abstract

Platelet hyaluronidase 2 enrichment in acute coronary syndromes: a conceivable role in monocyte-platelet aggregate formation

Cited by 8 publications

References 18 publications

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture

PTSD, major depression, and advanced transcriptomic age in brain tissue

Molecular Hallmarks of Ischemia with Non-Obstructive Coronary Arteries: The “INOCA versus Obstructive CCS” Challenge

Contact Info

Product

Resources

About