Objectives: Currently, cardiovascular risk associated with COVID-19 has been brought to people’s attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data.Methodology: Weighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm.Results: HIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation.Conclusions: The IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection

Radial artery deviation and reimplantation exhibits improved patency rates in both sexes and is associated with improved hemodynamics in a rat model.

Small diameter (< 6 mm) prosthetic vascular grafts continue to show very low long-term patency, but bioengineered vascular grafts show promising results in preclinical experiments. To assess a new scaffold source, we tested the use of decellularized fish swim bladder as a vascular patch and tube in rats. Fresh goldfish (Carassius auratus) swim bladder was decellularized, coated with rapamycin and then formed into patches or tubes for implantation in vivo. The rapamycin-coated patches showed decreased neointimal thickness in both the aorta and inferior vena cava patch angioplasty models. Rapamycin-coated decellularized swim bladder tubes implanted into the aorta showed decreased neointimal thickness compared to uncoated tubes, as well as fewer macrophages. These data show that the fish swim bladder can be used as a scaffold source for tissue-engineering vascular patches or vessels.

Tissue-engineered plant scaffolds have shown promising applications in in vitro studies. To assess the applicability of natural plant scaffolds as vascular patches, we tested decellularized leaf and onion cellulose in a rat inferior vena cava patch venoplasty model. The leaf was decellularized, and the scaffold was loaded with polylactic-co-glycolic acid (PLGA)-based rapamycin nanoparticles (nanoparticles). Nanoparticle-perfused leaves showed decreased neointimal thickness after implantation on day 14; there were also fewer CD68-positive cells and PCNA-positive cells in the neointima in the nanoparticle-perfused patches than in the control patches. Onion cellulose was decellularized, coated with rapamycin nanoparticles, and implanted in the rat; the nanoparticle-coated onion cellulose patches also showed decreased neointimal thickness. These data show that natural plant-based scaffolds may be used as novel scaffolds for tissue-engineered vascular patches. However, further modifications are needed to enhance patch strength for artery implantations.