Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with the Seurat 4, clusterProfiler, and Connectome software packages (V1.0.1). Immunostaining was performed with standard protocols. Within normal and aneurysmal aortae, three unique populations of cells that express smooth muscle cell (SMC) markers were identified (SMC1, SMC2, and SMCmod). A greater proportion of TAA SMCs clustered as a unique population, SMCmod, relative to the AAA SMCs (38% vs. 10–12%). These cells exhibited transcriptional features distinct from other SMCs, which were characterized by Igfbp2 and Tnfrsf11b expression. Genes upregulated in TAA SMCs were enriched for the Reactome terms “extracellular matrix organization” and “insulin-like growth factor (IGF) transport and uptake by IGF binding proteins (IGFBPs)”, indicating a role for Igfbp2 in TAA pathogenesis. Regulon analysis revealed transcription factors enriched in TAAs and AAAs. Validating these mouse bioinformatic findings, immunostaining demonstrated that both IGFBP2 and TNFRSF11B proteins increased in human TAAs compared to AAAs. These results highlight the unique cellular composition and transcriptional signature of SMCs in TAAs and AAAs. Future studies are needed to reveal the pathogenetic pathways of IGFBP2 and TNFRSF11B.
20 May 2024 in American Heart Journal Plus: Cardiology Research and Practice
Coronary in-stent restenosis (ISR) is a major clinical challenge of contemporary percutaneous revascularization and portends adverse cardiovascular outcomes. We aimed to evaluate gender, race, and ethnicity related outcomes in acute coronary syndromes (ACS) with ISR. Primary hospitalizations for ACS and ISR in the National Inpatient Sample database from 2016 to 2019 were included. Patients were stratified by gender, race, and ethnicity. The primary end points were all cause in-hospital mortality and coronary revascularization defined as composite of percutaneous coronary intervention (PCI), balloon angioplasty and/or coronary artery bypass grafting (CABG). During the study period, a nationally weighted total of 97,680 patients with ACS and ISR were included. There was substantial variation in comorbidities, with greatest burden among Black and Hispanic women. All-cause in-hospital mortality was 2.4 % in the study cohort, but significantly higher in women (2.1 % vs. 2.1 %; aOR: 1.282, 95 % CI: 1.174–1.4; p < 0.001) and revascularization rates were significantly lower in women (77 % vs 80.2 %; aOR: 0.891, 95 % CI: 0.862–0.921; p < 0.001). Compared to White men, all women except Hispanic women, had significantly higher likelihood of in-hospital mortality, while White women, Black men and women, and Hispanic men had lower odds of revascularization. There are significant gender, racial, and ethnic related differences in revascularization practices and clinical outcomes in patients with ACS and ISR with an adverse impact on women, racial and ethnic minorities in the U.S.
Background and Aims: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with increasing recognition of cardiovascular disease (CVD) as a major contributor to mortality. National data on cardiovascular deaths among individuals with IPF remains limited, and the impact of various disparities is unclear. The purpose of this study was to examine trends in the United States mortality rate involving cardiovascular deaths and pre‐existing pulmonary fibrosis. Methods: This was a retrospective cohort study conducted by gathering mortality data from the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research (CDC WONDER) publicly available database between the years 1999 and 2020. Death certificate data was extrapolated in this database, from which the subset of pulmonary fibrosis patients (ICD‐10 J84.1) were analyzed for cardiovascular‐related deaths (I00‐I99). Statistical analysis was then conducted via the Joinpoint regression software. Results: There were 47,814 cardiovascular‐related deaths with underlying pulmonary fibrosis between 1999 and 2000. The overall age‐adjusted mortality rate (AAMR) per 100,000 increased from 59.1 in 1999 to 134.5 in 2020 (Annual percent change [APC] = 3.37%, p < 10⁻⁶). Males had a higher AAMR and more pronounced increase than females (APC male = 4.09%, p < 10⁻⁶; APC female = 1.63%, p = 0.056). White individuals had the highest AAMR with the steeper upward mortality trend. Conclusions: Cardiovascular deaths with underlying pulmonary fibrosis have consistently increased from 1999 to 2020, highlighting the urgent need for preventative techniques and the necessity for additional targeted public health interventions based on demographic disparities.