The prevalence and clinical significance of intracranial vertebral artery terminated in posterior inferior cerebellar artery: A multicenter hospital-based study in China.

Objective: Intracranial vertebral artery terminated in the posterior inferior cerebellar artery (PICA-VA) is the most popular variant of the posterior inferior cerebellar artery, while its prevalence and clinical significance remained unclear. In the present study, we aimed to investigate the prevalence and clinical significance of PICA-VA. Methods: This was a multicenter hospital-based cross-sectional study. Patients were enrolled for cerebral MRI and MRA within 1 week of stroke onset. Clinical characteristics were recorded. PICA-VA is termed as a vertebral artery that does not communicate with the basilar artery but terminates in an ipsilateral PICA. We observed the prevalence of PICA-VA and identified a relationship between PICA-VA and vertebrobasilar stroke. Results: From 1 August 2015 to 31 May 2017, a total of 2,528 patients were enrolled in the present study. Among them, 95 patients (3.76%, 95/2,528) had the variation of PICA-VA, 51 of which (53.7%) were located on the right side. The prevalence of vertebrobasilar stroke was considerably higher in patients with PICA-VA than those without (40.2%, 37/92 vs. 17.1%, 417/2,436, p < 0.01). PICA-VA was an independent risk for vertebrobasilar stroke after being adjusted for a history of intracranial hemorrhage, diabetes, body mass index, and triglyceride. Conclusion: The present study showed that 3.76% of patients with acute stroke had PICA-VA, which independently increased the risk of acute vertebrobasilar stroke.

Gut Microbial Metabolite Trimethylamine N-Oxide Aggravates Pulmonary Hypertension.

Trimethylamine N-oxide (TMAO), a metabolite derived from intestine microbial flora, enhances vascular inflammation in a variety of cardiovascular diseases, and the bacterial communities associated with TMAO metabolism are higher in pulmonary hypertension (PH) patients. The effects of TMAO on PH, however, have not been elucidated. In the present study, circulating TMAO was found to be elevated in intermediate to high-risk PH patients when compared with healthy control or low-risk PH patients. In monocrotaline-induced rat PH models, circulating TMAO was elevated; and reduction of TMAO using 3,3-dimethyl-1-butanol (DMB) significantly decreased right ventricle systolic pressure and pulmonary vascular muscularization in both monocrotaline-induced rat PH and hypoxia-induced mouse PH models. RNA sequencing of rat lungs revealed that DMB treatment significantly suppressed the pathways involved in cytokine-cytokine receptor interaction and in cytokine and chemokine signaling. Protein-protein interaction analysis of the differentially expressed transcripts regulated by DMB showed five hub genes with a strong connectivity of proinflammatory cytokines and chemokines, including Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6. In vitro, TMAO significantly increased the expression of Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6 in bone-marrow-derived macrophage. Also, TMAO-treated conditioned medium from macrophage increased the proliferation and migration of pulmonary artery smooth muscle cells, but TMAO treatment did not change the proliferation or migration of pulmonary artery smooth muscle cells. In conclusion, our study demonstrates that TMAO is increased in severe PH, and the reduction of TMAO decreases pulmonary vascular muscularization and alleviates PH by suppressing the macrophage production of chemokines and cytokines.