-
Journal of the American College of... Aug 2023Valvular heart disease (VHD) is common and poses important challenges from the standpoints of diagnosis and therapeutic management. Clinical practice guidelines have... (Review)
Review
Valvular heart disease (VHD) is common and poses important challenges from the standpoints of diagnosis and therapeutic management. Clinical practice guidelines have been developed to help health care professionals to overcome these challenges and provide optimal management to patients with VHD. The American College of Cardiology, in collaboration with the American Heart Association, and the European Society of Cardiology, in collaboration with the European Association for Cardio-Thoracic Surgery, recently updated their guidelines on the management of VHD. Although these 2 sets of guidelines are generally concordant, there are some substantial differences between these guidelines, which may have significant implications for clinical practice. This review prepared on behalf of the EuroValve Consortium describes the consistencies and discrepancies between the guidelines and highlights the gaps in these guidelines and the future research perspectives to fill these gaps.
Topics: United States; Humans; Heart Valve Diseases; Heart; American Heart Association; Cardiology; Health Personnel
PubMed: 37587584
DOI: 10.1016/j.jacc.2023.05.061 -
Brain : a Journal of Neurology Nov 2023Moyamoya disease is an uncommon cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis and abnormal vascular network development. Ring...
Moyamoya disease is an uncommon cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis and abnormal vascular network development. Ring finger protein 213 (RNF213) has been identified as an important susceptibility gene for Asian patients, but researchers have not completely elucidated whether RNF213 mutations affect the pathogenesis of moyamoya disease. Using donor superficial temporal artery samples, whole-genome sequencing was performed to identify RNF213 mutation types in patients with moyamoya disease, and histopathology was performed to compare morphological differences between patients with moyamoya disease and intracranial aneurysm. The vascular phenotype of RNF213-deficient mice and zebrafish was explored in vivo, and RNF213 knockdown in human brain microvascular endothelial cells was employed to analyse cell proliferation, migration and tube formation abilities in vitro. After bioinformatics analysis of both cell and bulk RNA-seq data, potential signalling pathways were measured in RNF213-knockdown or RNF213-knockout endothelial cells. We found that patients with moyamoya disease carried pathogenic mutations of RNF213 that were positively associated with moyamoya disease histopathology. RNF213 deletion exacerbated pathological angiogenesis in the cortex and retina. Reduced RNF213 expression led to increased endothelial cell proliferation, migration and tube formation. Endothelial knockdown of RNF213 activated the Hippo pathway effector Yes-associated protein (YAP)/tafazzin (TAZ) and promoted the overexpression of the downstream effector VEGFR2. Additionally, inhibition of YAP/TAZ resulted in altered cellular VEGFR2 distribution due to defects in trafficking from the Golgi apparatus to the plasma membrane and reversed RNF213 knockdown-induced angiogenesis. All these key molecules were validated in ECs isolated from RNF213-deficient animals. Our findings may suggest that loss-of-function of RNF213 mediates the pathogenesis of moyamoya disease via the Hippo pathway.
Topics: Humans; Animals; Mice; Moyamoya Disease; Endothelial Cells; Hippo Signaling Pathway; Zebrafish; Neovascularization, Pathologic; Genetic Predisposition to Disease; Adenosine Triphosphatases; Ubiquitin-Protein Ligases
PubMed: 37399508
DOI: 10.1093/brain/awad225 -
Circulation Apr 2024Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α),...
BACKGROUND
Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive.
METHODS
Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global -knockout and vascular smooth muscle cell-specific -knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl; 0.5 mol/L; 42 days).
RESULTS
Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II- or CaCl-treated mice. Global or vascular smooth muscle cell-specific knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. , an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II- and CaCl-induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATAC-seq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process.
CONCLUSIONS
Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA.
PubMed: 38557060
DOI: 10.1161/CIRCULATIONAHA.123.065202 -
Otolaryngologic Clinics of North America Apr 2024Swallowing is an elaborate process that requires neuromuscular coordination. Pediatric esophageal dysphagia is broadly categorized into structural and nonstructural... (Review)
Review
Swallowing is an elaborate process that requires neuromuscular coordination. Pediatric esophageal dysphagia is broadly categorized into structural and nonstructural causes. The structural causes of pediatric esophageal dysphagia are related to processes that narrow the lumen of the esophagus. Esophageal strictures are the result of scar tissue formation within the lumen of the esophagus, leading to stenosis. Vascular rings and slings cause external compression of the esophagus. Diagnosis requires an esophagram and computed tomography or magnetic resonance imaging. Treatment is guided by the patient's symptoms and underlying diagnosis, although it often requires surgical intervention when symptomatic.
PubMed: 38575487
DOI: 10.1016/j.otc.2024.02.015 -
International Journal of Cardiology Jan 2024Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical...
Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.
Topics: Humans; Cicatrix; Consensus; Contrast Media; Gadolinium; Arrhythmogenic Right Ventricular Dysplasia; Cardiomyopathies; Arrhythmias, Cardiac
PubMed: 37844667
DOI: 10.1016/j.ijcard.2023.131447