Abstract 13595: Lactobacillus Supplementation Augments Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension

乳酸菌 医学 肺动脉高压 内科学 鼠李糖乳杆菌 植物乳杆菌 右心室肥大 失调 内分泌学 免疫学 心脏病学 肠道菌群 生物 生物化学 细菌 乳酸 遗传学 发酵
作者
Sasha Z. Prisco,Anna Park,Rashmi M. Raveendran,Kurt W. Prins
出处
期刊:Circulation [Ovid Technologies (Wolters Kluwer)]
卷期号:146 (Suppl_1)
标识
DOI:10.1161/circ.146.suppl_1.13595
摘要

Introduction: Gut microbiome dysbiosis induces hyperactivation of the immune systemic in multiple diseases. In pulmonary arterial hypertension (PAH), dysbiosis could therefore regulate right ventricular (RV) function because inflammatory glycoprotein 130 (GP130) signaling pathologically restructures RV microtubules and junctophilin-2 (JPH2) to promote RV dysfunction (RVD) in MCT rats. Interestingly, increases in intestinal Lactobacillus, an anti-inflammatory bacteria, by intermittent fasting enhance RV function in monocrotaline (MCT) rats. However, it is unknown if Lactobacillus supplementation can restructure the microbiome to suppress GP130-mediated RVD. Methods: Male rats were randomly allocated into 3 groups: control, MCT water gavage (MCT-water), and MCT Lactobacillus rhamnosus (4x10 7 CFU/day) gavage (MCT- Lactobacillus ) with treatments starting 2 weeks after MCT injection. Next-generation sequencing evaluated the composition of the bacterial and fungal components of the microbiome. SomaScan proteomics quantified levels of serum GP130 ligands. Immunoblots probed RV microtubule and JPH2 expression. Echocardiography and closed-chest pressure-volume (PV) loops determined RV function. Results: Lactobacillus supplementation restructured the micro/mycobiome, and concomitantly improved jejunal epithelial cell morphology. Serum proteomics revealed Lactobacillus treatment decreased circulating GP130 ligand levels which normalized RV microtubule and JPH2 protein expression. Finally, Lactobacillus reduced RV hypertrophy and fibrosis and enhanced RV function without changing PAH severity. Conclusions: Lactobacillus supplementation restructured the microbiome, dampened GP130 activation, normalized RV microtubule and JPH2 expression, and augmented RV function. Thus, Lactobacillus treatment could be a readily translatable approach to combat RVD in PAH.

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