Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study

Vancheri, Chiara; Morini, Elena; Prandi, Francesca Romana; Alkhoury, Elie; Celotto, Roberto; Romeo, Francesco; Novelli, Giuseppe; Amati, Francesca

doi:10.3390/genes12060939

Cited by 4 publications

(5 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main clinical data of the 96 subjects studied are summarized and reported in Table 1 ; a more detailed description is present in our previous study [ 26 ]. All the enrolled CAD and CTR patients are of white race/ethnicity.…”

Section: Resultsmentioning

confidence: 99%

“…The principal clinical characteristics of these patients are summarized and reported in Table 1 . A more detailed description of clinical data of these patients is available in Vancheri et al [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…Genome-wide methylation and miRNA sequencing (miRNA-seq) studies were performed in collaboration with “ICM-Plateforme de Génotypage-Séquençage” (Hôpital de la Pitié Salpêtrière, Paris, France) and GenoSplice ( , accessed on 31 December 2022) on two selected patients from CTR and CAD groups, matched for age and clinical features accordingly with their medical condition, already analyzed in another study ( Table 2 ) [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease

Vancheri

Morini

Prandi³

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Coronary heart disease (CHD), one of the leading causes of disability and death worldwide, is a multifactorial disease whose early diagnosis is demanding. Thus, biomarkers predicting the occurrence of this pathology are of great importance from a clinical and therapeutic standpoint. By means of a pilot study on peripheral blood cells (PBMCs) of subjects with no coronary lesions (CTR; n = 2) and patients with stable CAD (CAD; n = 2), we revealed 61 differentially methylated regions (DMRs) (18 promoter regions, 24 genes and 19 CpG islands) and 14.997 differentially methylated single CpG sites (DMCs) in CAD patients. MiRNA-seq results displayed a peculiar miRNAs profile in CAD patients with 18 upregulated and 32 downregulated miRNAs (FC ≥ ±1.5, p ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FCCAD = −2.97, p ≤ 0.05) associated to the hypermethylation of two sites (genomic coordinates: chr12:7073122-7073122 and chr12:7072599-7072599) located intragenic to the miR-200c/141 genomic locus (encoding hsa-miR-200c-3p) (p-value = 0.009) in CAD patients. We extended the hsa-miR-200c-3p expression study in a larger cohort (CAD = 72, CTR = 24), confirming its reduced expression level in CAD patients (FCCAD = −2; p = 0.02). However, when we analyzed the methylation status of the two CpG sites in the same cohort, we failed to identify significant differences. A ROC curve analysis showed good performance of hsa-miR-200c-3p expression level (AUC = 0.65; p = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R2 = 0.212, p < 0.005, Pearson r = 0.461) in CAD patients. Finally, a phenotypic correlation performed in the CAD group revealed lower hsa-miR-200c-3p expression levels in CAD patients affected by dyslipidemia (+DLP, n = 58) (p < 0.01). These results indicate hsa-miR-200c-3p as potential epi-biomarker for the diagnosis and clinical progression of CAD and highlight the importance of deeper studies on the expression of this miRNA to understand its functional role in coronary artery disease development.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease

Vancheri

Morini

Prandi³

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the meantime, until the role of alternative splicing in cardiovascular disease has been fully evaluated, alternatively spliced variants could serve as important biomarkers. For example, an investigation earlier this year focused on stable and unstable coronary artery disease uncovered a significant difference in the expression of long and short RECK alternatively spliced variants [ 79 ]. Although further research is required to fully explore the pathogenic mechanism of RECK splicing in plaque vulnerability, the RECK splice variants in the meantime could nevertheless act as promising biomarkers to monitor atherosclerosis.…”

Section: Alternative Splicing Based Therapeutic Strategiesmentioning

confidence: 99%

Alternative Splicing: A Key Mediator of Diabetic Vasculopathy

Cornelius¹,

Fulton²,

Margariti³

2021

Genes

View full text Add to dashboard Cite

Cardiovascular disease is the leading cause of death amongst diabetic individuals. Atherosclerosis is the prominent driver of diabetic vascular complications, which is triggered by the detrimental effects of hyperglycemia and oxidative stress on the vasculature. Research has extensively shown diabetes to result in the malfunction of the endothelium, the main component of blood vessels, causing severe vascular complications. The pathogenic mechanism in which diabetes induces vascular dysfunction, however, remains largely unclear. Alternative splicing of protein coding pre-mRNAs is an essential regulatory mechanism of gene expression and is accepted to be intertwined with cellular physiology. Recently, a role for alternative splicing has arisen within vascular health, with aberrant mis-splicing having a critical role in disease development, including in atherosclerosis. This review focuses on the current knowledge of alternative splicing and the roles of alternatively spliced isoforms within the vasculature, with a particular focus on disease states. Furthermore, we explore the recent elucidation of the alternatively spliced QKI gene within vascular cell physiology and the onset of diabetic vasculopathy. Potential therapeutic strategies to restore aberrant splicing are also discussed.

show abstract

“…The review by Hasimbegovic et al constitutes a well-written summary about the available findings on the role of alternative splicing in cardiovascular disease, focusing on atherosclerosis, myocardial infarction, heart failure, dilated cardiomyopathy, and circular RNAs in myocardial infarction [ 2 ]. Moreover, the interesting research study by Vancheri et al investigated the role of two RECK transcripts in coronary artery disease, showing their differential expression and proposing a functional role of these splice variants in the progression and development of this disease [ 3 ]. It should be mentioned that cardiovascular diseases constitute the leading cause of death among diabetic patients.…”

mentioning

confidence: 99%