Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite

Autor: Izabella Mogilnicka, Marcin Ufnal, Katarzyna Kraszewska, Mateusz Szudzik, Kinga Jaworska, Dawid Chabowski, Adrian Drapala, Emilia Samborowska
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
tight junctions
Metabolite
Hemodynamics
Trimethylamine
030204 cardiovascular system & hematology
Rats
Inbred WKY
Mass Spectrometry
lcsh:Chemistry
chemistry.chemical_compound
Feces
0302 clinical medicine
cardiovascular disease
Rats
Inbred SHR
lcsh:QH301-705.5
Spectroscopy
Chromatography
High Pressure Liquid
Tight junction
Chemistry
General Medicine
Computer Science Applications
medicine.medical_specialty
leaky gut
Renal function
TMAO
digestive system
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Methylamines
Internal medicine
medicine
Animals
Physical and Theoretical Chemistry
Claudin
Molecular Biology
bacterial metabolites
Heart Failure
Bacteria
Organic Chemistry
Blood flow
medicine.disease
Gastrointestinal Microbiome
Rats
intestinal barrier
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
Heart failure
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 6161, p 6161 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 17
ISSN: 1661-6596
1422-0067
Popis: Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut&ndash
blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut&ndash
blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology.
Databáze: OpenAIRE
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