Year: 2022
Type: dissertation
Study design: Observational Study
Abstract: While hypertension has been linked to various modifiable and fixed risk factors, the exact mechanisms behind blood pressure (BP) regulation and hypertension onset remain elusive. The rapid development in scientific branches studying genome, proteome, metabolome, and metagenome, coined collectively as ‘omics’, offer robust methods for studying complex biological phenomena in large population samples. The motivation of the current study was to assess the relation of the metabolome and metagenome with high BP in large Finnish cohorts. The specific aims were to estimate the association between gut microbiota and hypertension, to study the plasma metabolic profile of hypertension, and to elucidate if a family of circulating polyunsaturated fatty acid derived small molecule regulators of systemic inflammation, eicosanoids, are associated with BP. This and previous population studies demonstrate that gut microbiota is associated with human hypertension. Biologically reasonable pathophysiological mechanisms, including ones related to sodium intake, have been proposed to explain the phenomenon. However, the significance of these effects on population BP and health remains unclear and warrants further research. In this thesis, we demonstrate a strong association between circulating eicosanoids and BP in humans. We also use conventional statistical methods and multivariable machine learning models to define a metabolic profile of hypertension and blood pressure change using high abundance serum metabolic measures. Our results suggest that particularly serum lipids, and particularly low density lipoprotein-derived and very low density lipoprotein-derived cholesterol measures, and glucose metabolism abnormalities are associated with hypertension onset. Our studies improve the current knowledge on the associations of gut microbiota and circulating metabolites with BP. Metabolomics and metagenomics offer novel approaches to improve hypertension risk prediction and to discover potential targets for therapeutic intervention of elevated BP.
Source: UTUPub (University of Turku)
Author: Palmu, Joonatan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7020880138