Spontaneous coronary artery dissection: Overview of pathophysiology

Fusco, Stefania Angela Di; Rossini, Roberta; Zilio, Filippo; Pollarolo, Luigi; Uccio, Fortunato Scotto di; Iorio, Annamaria; Lucà, Fabiana; Gulizia, Michele Massimo; Gabrielli, Domenico; Colivicchi, Furio

doi:10.1016/j.tcm.2021.01.002

Cited by 30 publications

(23 citation statements)

References 72 publications

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“…Therefore, identification of the indirect factors in the regulatory pathway was the key to elucidating the genetic association. Circulating proteins are critical factors implicated in the development of SCAD ( 25 ). We found that the shared genetic variants were strongly associated with many circulating proteins and that the associated proteins have specific biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the GWAS identified loci containing genes that encode proteins or regulate the expression of proteins involved in arterial wall structure and/or function. Circulating proteins such as TGF β receptor, collagen α1 chain, fibrillin, endotelin-1, ribosome maturation factor, and talin 1 were implicated in the development of SCAD ( 25 ). Currently, multiple cytokines, including interleukins, interferon, the tumor necrosis factor superfamily, colony stimulating factor, chemotactic factor, growth factor and so on, have all been demonstrated to play a critical role in SCAD.…”

Section: Introductionmentioning

confidence: 99%

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Association of Circulating Cathepsin B Levels With Blood Pressure and Aortic Dilation

Chai

Tian

Yang

et al. 2022

Front. Cardiovasc. Med.

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Hypertension is a key risk factor for spontaneous coronary artery dissection (SCAD) and aortic dilation. Circulating proteins play key roles in a range of biological processes and represent a major source of druggable targets. The aim of this study was to identify circulating proteins that were associated with blood pressure (BP), SCAD and aortic dilation. We identified shared genetic variants of BP and SCAD in genome-wide association studies, searched for circulating protein affected by these variants and examined the association of circulating protein levels with BP, aortic aneurysm and dissection (AAD) and aortic diameters by integrating data from circulating protein quantitative trait loci (pQTL) studies and genome wide association study (GWAS) in individuals from the UK Biobank using two-sample Mendelian randomization analysis methods. Single nucleotide polymorphisms (SNPs) in JAG1, ERI1, ULK4, THSD4, CMIP, COL4A2, FBN1, FAM76B, FGGY, NUS1, and HNF4G, which were related to extracellular matrix components, were associated with both BP and SCAD. We found 49 significant pQTL signals among these SNPs. The regulated proteins were encoded by MMP10, IL6R, FIGF, MMP1, CTSB, IGHG1, DSG2, TTC17, RETN, POMC, SCARF2, RELT, and GALNT16, which were enriched in biological processes such as collagen metabolic process and multicellular organism metabolic process. Causal associations between BP and AAD and aortic diameters were detected. Significant associations between circulating levels of cathepsin B, a well-known prorenin processing enzyme, and BP and aortic diameters were identified by using several Mendelian randomization analysis methods and were validated by independent data.ConclusionThe present study identified the association between circulating cathepsin B and BP and aortic diameters. The findings indicated that BP-associated genetic variants may influence aortic dilation risk by circulating proteins that regulate BP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Circulating Cathepsin B Levels With Blood Pressure and Aortic Dilation

Chai

Tian

Yang

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…Indeed, the GWAS identified loci containing genes that encode proteins involved in arterial vascular wall structure and function. Circulating proteins such as TGF β receptor, collagen α1 chain, fibrillin, endotelin-1, ribosome maturation factor, and talin 1 were implicated in the development of SCAD ( 28 ). Cytokines such as the tumor necrosis factor superfamily, growth factor, interferon, interleukins, colony stimulating factor, and chemotactic factor play important roles in AAD.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification of Associations of Circulating Molecules With Spontaneous Coronary Artery Dissection and Aortic Aneurysm and Dissection

Chai

Tian

Yang

et al. 2022

Front. Cardiovasc. Med.

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Circulating proteins play functional roles in various biological processes and disease pathogenesis. The aim of this study was to highlight circulating proteins associated with aortic aneurysm and dissection (AAD) and spontaneous coronary artery dissection (SCAD). We examined the associations of circulating molecule levels with SCAD by integrating data from a genome-wide association study (GWAS) of CanSCAD and 7 pQTL studies. Mendelian randomization (MR) analysis was applied to examine the associations between circulating molecule levels and AAD by using data from UK Biobank GWAS and pQTL studies. The SCAD-associated SNPs in 1q21.2 were strongly associated with circulating levels of extracellular matrix protein 1 (ECM1) and 25 other proteins (encoded by CTSS, CAT, CNDP1, KNG1, SLAMF7, TIE1, CXCL1, MBL2, ESD, CXCL16, CCL14, KCNE5, CST7, PSME1, GPC3, MAP2K4, SPOCK3, LRPPRC, CLEC4M, NOG, C1QTNF9, CX3CL1, SCP2D1, SERPINF2, and FN1). These proteins were enriched in biological processes such as regulation of peptidase activity and regulation of cellular protein metabolic processes. Proteins (FGF6, FGF9, HGF, BCL2L1, and VEGFA) involved in the Ras signaling pathway were identified to be related to AAD. In addition, SCAD- and AAD-associated SNPs were associated with cytokine and lipid levels. MR analysis showed that circulating ECM1, SPOCK3 and IL1b levels were associated with AAD. Circulating levels of low-density lipoprotein cholesterol and small very-low-density lipoprotein particles were strongly associated with AAD. The present study found associations between circulating proteins and lipids and SCAD and AAD. Circulating ECM1 and low-density lipoprotein cholesterol may play a role in the pathology of SCAD and AAD.

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“…Intravascular imaging -optical coherence tomography (OCT) and intravascular ultrasound (IVUS) -can clarify the ambiguous angiographic appearance of SCAD. 14,15,21,22 The optimal management and treatment strategy are not yet well defined. Conservative treatment with medical therapy is preferred for stable patients without ongoing chest pain and/or impaired flow.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous coronary artery dissection: an Italian single centre experience

Solinas¹,

Alabrese

Cattabiani³

et al. 2021

Journal of Cardiovascular Medicine

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Aims Spontaneous coronary artery dissection (SCAD) is an emerging cause of acute myocardial infarction (AMI) in young women without a typical cardiovascular risk profile. Knowledge on SCAD is based on observational studies and is still scarce. The aim of this monocentric observational study was to evaluate the predisposing factors, clinical features and prognosis of SCAD patients.Methods Between 2013 and 2020, 58 patients with angiographic diagnosis of SCAD were identified in our centre with an overall prevalence of 0.9% among patients admitted for AMI (58 of 6414 patients). ResultsThe mean age was 54W 11 years and the majority were women (n U 50, 86%) with one or fewer cardiovascular risk factors (n U 35, 60%). The prevalence of Fibromuscolar Dysplasia (FMD) was 39% (7 of 18 screened patients). The rate of major adverse cardiovascular and cerebrovascular events (MACCEs) was used to assess the prognosis. Out-of-hospital cardiac arrest because of ventricular fibrillationo was observed in four (7%) patients. The majority of patients (n U 51, 88%) were treated conservatively without revascularization. The inhospital and 30-day clinical course was uneventful in most patients (n U 54, 93%) with two cardiac deaths. During a median follow-up of 12 months, there were no further deaths. The global rate of SCAD recurrence was significant (n U 8, 14%) but predictors have not been identified. ConclusionAlthough overall survival seems good, SCAD is a potentially malignant, not rare disease, which can present with sudden cardiac death and not uncommon recurrence. Prognostic stratification and optimal management of SCAD patients remain to be defined.

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Spontaneous coronary artery dissection: Overview of pathophysiology

Cited by 30 publications

References 72 publications

Association of Circulating Cathepsin B Levels With Blood Pressure and Aortic Dilation

Association of Circulating Cathepsin B Levels With Blood Pressure and Aortic Dilation

Genome-Wide Identification of Associations of Circulating Molecules With Spontaneous Coronary Artery Dissection and Aortic Aneurysm and Dissection

Spontaneous coronary artery dissection: an Italian single centre experience

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