Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb 8;24(4):3385.
doi: 10.3390/ijms24043385.

Gut Molecules in Cardiometabolic Diseases: The Mechanisms behind the Story

Andreea-Ioana Inceu  1 , Maria-Adriana Neag  1 , Anca-Elena Craciun  2 , Anca-Dana Buzoianu  1
Affiliations
Review

Gut Molecules in Cardiometabolic Diseases: The Mechanisms behind the Story

Andreea-Ioana Inceu et al. Int J Mol Sci. .

Abstract

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases.

Keywords: atherosclerosis; atrial fibrillation; diabetes mellitus; gut hormones; gut microbiota; heart failure; inflammation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The signaling pathways involved in GLP-1 protective effects in the pancreatic β-cells. The activation of GLP-1R leads to multiple effects in β-2 cells. The direct signaling pathways are represented in black arrows and the mediators involved are depicted in orange boxes. The indirect molecular cascades comprise green arrows that involve additional mediators represented in yellow boxes. The two-headed arrow represents the bidirectional relationship between PKC and Akt-PKB. GLP-1: glucagon-like peptide-; GLP-1R: GLP-1 receptor; cAMP: Adenosine 3’,5’-cyclic monophosphate; PKA: protein kinase A; EPAC2: exchange protein directly activated by cAMP 2; MAPK: mitogen-activated protein kinase; CREB: cAMP response element binding protein; TORC2: transducer of regulated CREB activity 2; PI-3K: Phosphatidylinositol-4,5-bisphosphate 3-kinase; PKC: protein kinase C; Akt-PKB: Akt-protein kinase B; JNK: Jun N-terminal kinase; BCL-2: B-cell lymphoma 2.
Figure 2
Figure 2
The effects of incretins in atherogenesis. NO: nitric oxide; ROS: reactive oxygen species; EC: endothelial cells; SMC: smooth muscle cells; MMP: metalloproteinase; EPCs: endothelial progenitor cells.
See this image and copyright information in PMC

References

    1. Townsend N., Wilson L., Bhatnagar P., Wickramasinghe K., Rayner M., Nichols M. Cardiovascular disease in Europe: Epidemiological update 2016. Eur. Heart J. 2016;37:3232–3245. doi: 10.1093/eurheartj/ehw334. - DOI - PubMed
    1. Visseren F.L.J., MacH F., Smulders Y.M., Carballo D., Koskinas K.C., Bäck M., Benetos A., Biffi A., Boavida J.M., Capodanno D., et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 2021;42:3227–3337. doi: 10.1093/eurheartj/ehab484. - DOI - PubMed
    1. Conrad N., Judge A., Tran J., Mohseni H., Hedgecott D., Crespillo A.P., Allison M., Hemingway H., Cleland J.G., McMurray J.J.V., et al. Temporal trends and patterns in heart failure incidence: A population-based study of 4 million individuals. Lancet. 2018;391:572–580. doi: 10.1016/S0140-6736(17)32520-5. - DOI - PMC - PubMed
    1. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Böhm M., Burri H., Butler J., Celutkiene J., Chioncel O., et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021;42:3599–3726. doi: 10.1093/eurheartj/ehab368. - DOI - PubMed
    1. Tsao C.W., Lyass A., Enserro D., Larson M.G., Ho J.E., Kizer J.R., Gottdiener J.S., Psaty B.M., Vasan R.S. Temporal Trends in the Incidence of and Mortality Associated with Heart Failure with Preserved and Reduced Ejection Fraction. JACC Heart Fail. 2018;6:678–685. doi: 10.1016/j.jchf.2018.03.006. - DOI - PMC - PubMed

MeSH terms