Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Background: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. Methods: We developed a sensitive high-pressure liquid chromatography technique to quantify dietary GGPP and conducted proteomics, qualitative real-time polymerase chain reaction screening, and Western blot to determine signaling cascades, gene expression, protein–protein interaction, and protein membrane trafficking in wild-type and transgenic rats. Results: GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate–rich garlic extracts. In human pulmonary artery smooth muscle cells treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2 (Rho associated coiled-coil containing protein kinase 2)/Rab10 (Ras-related protein rab-10) signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and human pulmonary artery smooth muscle cells upregulated the expression of Ca ²⁺ -sensing receptor (CaSR) and HIMF (hypoxia-induced mitogenic factor), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10 knockdown almost abrogated hypoxia-promoted CaSR membrane trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed a high GGPP diet, blood GGPP levels were increased. This abolished statin-lowering effects on plasma GGPP, and also on hypoxia-enhanced RhoA activity of blood monocytes that was rescued by garlic extracts. Conclusions: There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of RhoA-ROCK2 cascade activation and Rab10-faciliated CaSR membrane trafficking with subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.

We aimed to summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% CI : 1.90-4.29) or high ( CI : 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 ( P = 0.0004 and P = 0.0003, respectively) and day 28/35 ( P < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All P < 0.001). In conclusion, our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.

Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single‐stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA‐binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.

Background: Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). Methods: Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. Results: Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. Conclusion: Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.

The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We searched several databases and preprint platforms using core terms ‘eosinophil’, ‘myocardial infarction’, ‘ischemic stroke’, and ‘venous thromboembolism’ (VTE), among others. Studies comparing the odds ratios (ORs) or risk ratios (RRs) of EOSs with the abovementioned diseases were eligible. Overall, 22 studies were included. A high EOS count was associated with acute coronary artery thrombosis events (OR: 1.23, 95% CI: 1.15–1.32), short‐term cerebral infarction and mortality (RR: 2.87, 95% CI: 1.49–5.51). The short‐term risk of VTE was more common in patients with EOS‐related diseases (RR: 6.52, 95% CI: 2.42–17.54). For coronary artery disease, a high EOS count was a protective factor against 6‐month to 1‐year mortality (RR: 0.56, 95% CI: 0.45–0.69) but was associated with long‐term mortality (RR: 1.64, 95% CI: 1.25–2.14). Therefore, we conclude that for coronary artery thrombosis, EOS count is not associated with AMI events in general population. It may be associated with NSTEMI and STEMI in CAD patients, but more studies are needed to confirm this. In addition, EOS count is associated with an increased risk of both short‐ and long‐term mortality but is not predictive of the composite endpoints. For cerebral artery thrombosis, EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short‐term prognosis. For VTEs, EOS count was a risk factor for some patients, especially those with acute‐phase EOS‐related diseases.