UPLC-MS-Based Serum Metabolomics Reveals Potential Biomarkers of Ang II-Induced Hypertension in Mice

Abstract

Hypertension is caused by polygenic inheritance and the interaction of various environmental factors. Abnormal function of the renin-angiotensin-aldosterone system (RAAS) is closely associated with changes in blood pressure. As an essential factor in the RAAS, angiotensin II (Ang II) contributes to vasoconstriction and inflammatory responses. However, the effects of overproduction of Ang II on the whole body-metabolism have been unclear. In this study, we established a hypertensive mouse model by micro-osmotic pump perfusion of Ang II, and the maximum systolic blood pressure reached 140 mmHg after 2 weeks. By ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolites in the serum of hypertensive model and control mice were analyzed. Partial least squares discriminant analysis (PLS-DA) in both positive and negative ionization modes showed clear separation of the two groups. Perfusion of Ang II induced perturbations of multiple metabolic pathways in mice, such as steroid hormone biosynthesis and galactose metabolism. Tandem mass spectrometry revealed 40 metabolite markers with potential diagnostic value for hypertension. Our data indicate that non-targeted metabolomics can reveal biochemical pathways associated with Ang II-induced hypertension. Although researches about the clinical use of these metabolites as potential biomarkers in hypertension is still needed, the current study improves the understanding of systemic metabolic response to sustained release of Ang II in hypertensive mice, providing a new panel of biomarkers that may be used to predict blood pressure fluctuations in the early stages of hypertension.

Probiotics Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 prevent high blood pressure via modulating the gut microbiota composition and host metabolic products

“…Moreover, Alistipes was associated with the level of bile acid, influencing portal hypertension though farnesoid-X receptor ( 25 , 26 ); therefore, we speculated that Alistipes might affect the host hypertension via bile acid metabolism. Additionally, the strong negative correlation between Alistipes and steroid hormone biosynthesis may suggest that Alistipes could reduce the BP by regulating steroid hormone biosynthesis, which is associated with hypertension ( 27 ). The potential mechanisms underlying the link between Alistipes and BP certainly need more evidence based on future well-controlled studies.…”