bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.09.26.508411

Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease Associated Coronary Arteritis

Rashid, A.·Malik, R.·Malik, Z.·Shaikh, G.·Hussain, Z.·Al-Dubai, A.·Hussain, A.
View original source ↗Export metadata ↓

Abstract

Kawasaki Disease (KD) is a childhood vasculitis primarily affecting medium-sized arteries, which can lead to severe complications, particularly with respect to coronary artery disease (CAD). The impact of thermal stress on KD coronary artery pathogenesis, in association with prolonged fever and inflammation, remains unclear. In this study, we hypothesized that altered gene expression (GE) of angiogenesis-inducing Heat Shock Proteins (HSPs) is associated with KD-CAD through pro-inflammation. Transcriptomic analysis was performed using the three largest KD peripheral blood studies in the clinical literature (KD1-KD3), and one study direct from coronary artery tissue (KD4). The analysis revealed a significant increase in TNF and NFKB1 GE, indicating the presence of inflammation based on gene expression profiles. Gene set enrichment analysis (GSEA) of KD1-KD3 datasets identified inflammatory pathways, including TNFA signaling via NFKB, IL6 JAK STAT 3 Signalling, and p53 (Heat Shock Protein 90). The study also focused on specific HSPs known to be associated with angiogenesis, namely HSPB1, HSPA1A, and HSP90AB1. The temporal transcript model (TTM) consistently showed up-regulation of pro-inflammatory genes VEGF-A, TNF, and NFKB1, as well as up-regulation of HSPA1A. GSEA revealed gene ontology pathways associated with VEGF production. These findings suggest that the binding of VEGF-A or VEGF-B to their receptors could potentially impact the coronary artery in KD. Additionally, the up-regulation of the gene HSPAB1 in KD has not been described previously. In contrast, KD4 showed no differential GE for the studied genes potentially related to end-stage KD. This study provides valuable insights into VEGF and HSPs in KD-associated inflammation. Future research should focus on developing a VEGF-HSP CAD model to explore implications for KD biomarking as well as developing precision management strategies.

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rashid, A., Malik, R., Malik, Z., Shaikh, G., Hussain, Z., Al-Dubai, A., Hussain, A.. 2022-09-28. Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease Associated Coronary Arteritis. https://doi.org/10.1101/2022.09.26.508411

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Genome-wide diversity across 130 years reveals drastic post-bottleneck genetic erosion in a recovering population of golden eagles (Aquila chrysaetos)

Many wild populations have experienced severe human-induced declines, but the genetic consequences of such bottlenecks are often poorly understood. In Finland, as well as in many other countries, golden eagles were heavily persecuted during the 19th-20th centuries, disappearing from southern regions and reaching their lowest population size in the 1950-1960s. Although conservation efforts facilitated demographic recovery, the long-term genomic consequences of the bottleneck remained unknown. Here, we used whole-genome sequencing data spanning 136 years to evaluate patterns of genetic diversity in 26 Finnish golden eagles before, during, and after the mid-20th century bottleneck. We found substantial loss of genetic variation, including an 82% reduction in genome-wide heterozygosity, a 42% decline in nucleotide diversity, a 67% reduction in Watterson's theta, and a substantial loss of variable sites. Analyses of the site frequency spectrum and Tajima's D confirmed historical population contraction, and runs of homozygosity analysis indicated elevated post-bottleneck inbreeding. These results indicate strong genetic erosion in Finnish golden eagles despite the census size recovery. Therefore, incorporating genomic indicators in conservation monitoring and performing regional assessments are necessary to guide management and preserve biodiversity in line with the Global Biodiversity Framework's goal of maintaining genetic variation.

genomics↗
bioRxiv2026

Long-read analysis of complete human 5S rDNA arrays reveals a zoned organization with two-state unit methylation linked to chromatin architecture

Despite the fundamental importance of the 5S ribosomal DNA (rDNA) to all cellular life, the landscape of its units by position along its array has remained poorly understood. Here, recent telomere-to-telomere long-read sequencing is used to resolve 5S rDNA arrays from flank to flank and to follow the state of each unit along single molecules. The array is zoned at both the sequence and the epigenetic level. Notably, methylation is bimodal at the level of the unit, and the combination of low-methylation and high-methylation units gives rise to the overall methylation pattern of the array. Moreover, the average number of low-methylation units remains relatively constant regardless of array length. Chromatin fiber sequencing (Fiber-seq) data further show that low-methylation units are more accessible, have lower nucleosome occupancy and are more frequently footprinted at the TFIIIB-binding site, consistent with analyses of ATAC-seq and ChIP-seq data from cell lines. Across species, this pattern is shared among apes, whereas other species show diverse patterns. These results provide a unit-resolved view of the human 5S rDNA array and reveal a zone-specific organization of unit methylation that is associated with chromatin architecture.

genomics↗
bioRxiv2026

Using Oyster Genomics to Understand Human Health

As sessile filter feeders that experience continuous environmental exposure, oysters, particularly Crassostrea virginica, offer a unique opportunity to understand how environmental exposure alters the genome and influence health. Furthermore, oysters must be sorted by size for market value for premium size and taste. However, it requires intensive labor, specialized equipment (tumblers), and is susceptible to environmental risks like pollution. Therefore, it is desirable to produce uniform oysters without machines. However, limitations in the previous reference genome [2] have constrained our understanding of how genes are organized and maintained in oyster populations. To this end, we harvested 240 adult oysters in same location, 120 extremely large size and 120 extremely small, controlled with all confounding factors such as age and water temperature. We perform a genome wise associate study (GWAS) using next generation whole genome sequencing, aiming to discover genomic regions associated with oyster size. Using PacBio HiFi, Illumina, and Hi-C technologies, we generated a 99.7% complete chromosome-level genome assembly for C. virginica (NCBI RefSeq GCF_053477285.1) [75]. We identified a ~13 Mb region on chromosome 1 uniquely expanded in C. virginica and enriched for innate immune and stress-response genes. To evaluate whether these structural features are reflected at the population level, we then conducted a k-mer analysis. This revealed differential sequence patterns by size, including enrichment of bacterial DNA in smaller individuals and host variation at the RNF213 locus within this region. By highlighting genome structure as a mediator of immune resilience, this work supports the use of oysters as sentinels to advance out understanding of how the dynamic reassembly of the genome due to environmental exposures influence health in human populations.

genomics↗