Arteries and veins develop different types of occlusive diseases and respond differently to injury. The biological reasons for this discrepancy are not well understood, which is a limiting factor for the development of vein-targeted therapies. This study contrasts human peripheral arteries and veins at the single-cell level, with a focus on cell populations with remodeling potential.
View Article and Find Full Text PDFThe venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses.
View Article and Find Full Text PDFIntroduction: The molecular transformation of the human preaccess vein after arteriovenous fistula (AVF) creation is poorly understood. This limits our ability to design efficacious therapies to improve maturation outcomes.
Methods: Bulk RNA sequencing (RNA-seq) followed by paired bioinformatic analyses and validation assays were performed in 76 longitudinal vascular biopsies (veins and AVFs) from 38 patients with stage 5 chronic kidney disease or end-stage kidney disease undergoing surgeries for 2-stage AVF creation (19 matured, 19 failed).
Background: Systemic cytokines are elevated in patients with chronic kidney disease (CKD) and on hemodialysis compared with the general population. However, whether cytokine levels interfere with vascular remodeling, increasing the risk of arteriovenous fistula (AVF) failure, remains unknown.
Methods: This is a case-control study of 64 patients who underwent surgery for AVF creation (32 with AVF maturation failure and 32 matching controls with successful maturation).
Pharmacological activation of integrin CD11b/CD18 (αβ, Mac-1, and CR3) shows anti-inflammatory benefits in a variety of animal models of human disease, and it is a novel therapeutic strategy. Reasoning that genetic models can provide an orthogonal and direct system for the mechanistic study of CD11b agonism, we present in this study, to our knowledge, a novel knock-in model of constitutive active CD11b in mice. We genetically targeted the gene (which codes for CD11b) to introduce a point mutation that results in the I332G substitution in the protein.
View Article and Find Full Text PDFRationale & Objective: Improving arteriovenous fistula (AVF) outcomes requires better understanding of the biology underlying maturation or failure. Our current knowledge of maturation relies on extrapolation from other vascular pathologies, which does not incorporate unique aspects of AVF remodeling. This study compares the RNA expression of pre-access (native) veins and AVFs with distinct maturation outcomes.
View Article and Find Full Text PDFThe homeostatic lung protective effects of alpha-1 antitrypsin (A1AT) may require the transport of circulating proteinase inhibitor across an intact lung endothelial barrier. We hypothesized that uninjured pulmonary endothelial cells transport A1AT to lung epithelial cells. Purified human A1AT was rapidly taken up by confluent primary rat pulmonary endothelial cell monolayers, was secreted extracellularly, both apically and basolaterally, and was taken up by adjacent rat lung epithelial cells co-cultured on polarized transwells.
View Article and Find Full Text PDFThe role of short, large or intermediate normal alleles (ANs) of the ataxin-2 gene in generating expanded alleles (EAs) causing spinocerebellar ataxia type 2 (SCA2) is poorly understood. It has been postulated that SCA2 prevalence is related to the frequency of large ANs. SCA2 shows the highest worldwide prevalence in Cuban population, which is therefore a unique source for studying the relationship between the frequency of large and intermediate alleles and the frequency of SCA2 mutation.
View Article and Find Full Text PDFThe objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1-3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families.
View Article and Find Full Text PDFWe assessed maximal saccade velocity (MSV) in 82 spinocerebellar ataxia type 2 (SCA2) patients and 80 controls, correlating it to disease duration, polyglutamine expansion size, age at onset, ataxia score, age, and sex. Little overlap with normal values was found even at earliest stages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutamine size and less by disease duration, whereas the reverse was found for ataxia score.
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