Vascular reactivity stimulated by TMA and TMAO: Are perivascular adipose tissue and endothelium involved?

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Carolina Baraldi A RestiniStephanie W Watts

Abstract

Trimethylamine (TMA), formed by intestinal microbiota, and its Flavin-Monooxygenase 3 (FMO3) product Trimethylamine-N-Oxide (TMAO), are potential modulators of host cardiometabolic phenotypes. High circulating levels of TMAO are associated with increased risk for cardiovascular diseases. We hypothesized that TMA/TMAO could directly change the vascular tone. Perivascular adipose tissue (PVAT) helps to regulate vascular homeostasis and may also possess FMO3. Thoracic aorta with(+) or without(-) PVAT, also + or - the endothelium (E), of male Sprague Dawley rats were isolated for measurement of isometric tone in response to TMA/TMAO (1nM-0.5 M). Immunohistochemistry (IHC) studies were done to identify the presence of FMO3. TMA and TMAO elicited concentration-dependent arterial contraction. However, at a maximally achievable concentration (0.2 M), contraction stimulated by TMA was of a greater magnitude (141.5 ± 16% of maximum phenylephrine contraction) than that elicited by TMAO (19.1 ± 4.03%) with PVAT and endothelium intact. When PVAT was preserved, TMAO-induced contraction was extensively reduced the presence (19.1 ± 4.03%) versus absence of E (147.2 ± 20.5%), indicating that the endothelium plays a protective role against TMAO-...Continue Reading

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Citations

Jun 19, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Carla B P SilvaRita C Tostes
Jun 25, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura BordoniRobert A Olek
May 15, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Camilla F WenceslauR Clinton Webb
Aug 19, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kinga JaworskaMarcin Ufnal

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