Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1 LDS mice by single-cell transcriptomics to identify molecular determinants of this vulnerability.

Nuclear Smooth Muscle α-actin Participates in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult-onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by diverse childhood-onset vascular diseases. Here we show that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors. The p.

Intrinsic expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of LDS mice by single cell and spatial transcriptomics.

Augmenting Mitochondrial Respiration in Immature Smooth Muscle Cells with an Pathogenic Variant Mitigates Moyamoya-like Cerebrovascular Disease.

pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusion of the distal internal carotid arteries. A smooth muscle cell (SMC)-specific knock-in mouse model () inserted the mutation into 67% of aortic SMCs, whereas explanted SMCs were uniformly heterozygous. SMCs fail to fully differentiate and maintain stem cell-like features, including high glycolytic flux, and increasing oxidative respiration (OXPHOS) with nicotinamide riboside (NR) drives the mutant SMCs to differentiate and decreases migration.

Reduced Pulmonary Artery Distensibility Predicts Persistent Pulmonary Hypertension and 2-Year Mortality in Patients with Severe Aortic Stenosis Undergoing TAVR.

Rationale And Objectives: Post-TAVR persistent pulmonary hypertension (PH) is a better predictor of poor outcome than pre-TAVR PH. In this longitudinal study we sought to evaluate whether pulmonary artery (distensibility (D) measured on preprocedural ECG-gated CTA is associated with persistent-PH and 2-year mortality after TAVR.

Materials And Methods: Three hundred and thirty-six patients undergoing TAVR between July 2012 and March 2016 were retrospectively included and followed for all-cause mortality until November 2017.

Smooth Muscle Cell Klf4 Expression Is Not Required for Phenotype Modulation or Aneurysm Formation in Marfan Syndrome Mice-Brief Report.

Background: Smooth muscle cell (SMC) phenotypic reprogramming toward a mixed synthetic-proteolytic state is a central feature of aortic root aneurysm in Marfan syndrome (MFS). Previous work identified as a potential mediator of SMC plasticity in MFS.

Methods: MFS () mouse strains with an inducible vascular SMC fluorescent reporter () with or without SMC-specific deletion of exons 2 to 3 () were generated.

Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice.

Background: The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS.

Methods: Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms.

Nuclear Smooth Muscle α-actin in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by childhood-onset diverse vascular diseases. Our data indicate that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors, and the p.R179 variant decreases nuclear localization of αSMA.

Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) in Uncomplicated Type B Aortic Dissection: Study Design and Rationale.

Purpose: To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD).

Materials And Methods: The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model.

Midterm Outcomes in Type A Aortic Dissection Repair With and Without Malperfusion in a Hybrid Operating Room.

Treatment approach to type A aortic dissection with malperfusion, immediate open aortic repair vs upfront endovascular treatment, remains controversial. From January 2017 to July 2021, 301 consecutive type A repairs were evaluated at our institution. Starting in 2019, all type A aortic dissections were performed in a fixed-fluoroscopy, hybrid operating room.

Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling.

Many cell-based therapies are challenged by the poor localization of introduced cells and the use of biomaterial scaffolds with questionable biocompatibility or bio-functionality. Endothelial progenitor cells (EPCs), a popular cell type used in cell-based therapies due to their robust angiogenic potential, are limited in their therapeutic capacity to develop into mature vasculature. Here, we demonstrate a joint delivery of human-derived endothelial progenitor cells (EPC) and smooth muscle cells (SMC) as a scaffold-free, bi-level cell sheet platform to improve ventricular remodeling and function in an athymic rat model of myocardial infarction.

Total aortic arch replacement using a frozen elephant trunk device: Results of a 1-year US multicenter trial.

Objective: In this prospective US investigational device exemption trial, we assessed the safety and 1-year clinical outcomes of the Thoraflex Hybrid device (Terumo Aortic) for the frozen elephant trunk technique to repair the ascending aorta, aortic arch, and descending thoracic aorta.

Methods: For the trial, which involved 12 US sites, 65 patients without rupture were recruited into the primary study group, and 9 patients were recruited into the rupture group. All patients underwent open surgical repair of the ascending aorta, aortic arch, and descending thoracic aorta in cases of aneurysm and/or dissection.

Smad3 regulates smooth muscle cell fate and mediates adverse remodeling and calcification of the atherosclerotic plaque.

Atherosclerotic plaques consist mostly of smooth muscle cells (SMC), and genes that influence SMC phenotype can modulate coronary artery disease (CAD) risk. Allelic variation at 15q22.33 has been identified by genome-wide association studies to modify the risk of CAD and is associated with the expression of in SMC.

Inter-observer variability of expert-derived morphologic risk predictors in aortic dissection.

Objectives: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning.

Methods: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow.

Midterm Outcomes of Endovascular Repair of Aortic Arch Aneurysms with the Gore Thoracic Branch Endoprosthesis.

Objective: Aortic aneurysms involving aortic arch vessels are anatomically unsuitable for standard thoracic endovascular repair (TEVAR) without cervical debranching of the arch vessels. Three year outcomes of a single branched thoracic endograft following previous publication of peri-operative and one year outcomes are reported.

Methods: This was a multicentre feasibility trial of the GORE TAG Thoracic Branch Endoprosthesis (TBE), a thoracic endovascular graft incorporating a single retrograde branch for aortic arch vessel perfusion.

Embryologic Origin Influences Smooth Muscle Cell Phenotypic Modulation Signatures in Murine Marfan Syndrome Aortic Aneurysm.

Background: Aortic root smooth muscle cells (SMC) develop from both the second heart field (SHF) and neural crest. Disparate responses to disease-causing variants by these lineages are proposed to promote focal aortic root aneurysm formation in Marfan syndrome (MFS), but lineage-stratified SMC analysis in vivo is lacking.

Methods: We generated SHF lineage-traced MFS mice and performed integrated multiomic (single-cell RNA and assay for transposase-accessible chromatin sequencing) analysis stratified by embryological origin.

Tetralogy of Fallot and Aortic Dissection: Implications in Management.

We present the case of a 61-year-old man with tetralogy of Fallot postrepair and mechanical aortic valve replacement with an aortic root/ascending/arch aneurysm with chronic type A aortic dissection. He underwent uncomplicated aortic root and total arch replacement. Continued surveillance for aortic aneurysm is necessary in the tetralogy of Fallot population.