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
. 2024 Jan 23;13(2):70.
doi: 10.3390/biology13020070.

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Azra Kulovic-Sissawo  1   2 , Carolina Tocantins  1   2   3   4   5 , Mariana S Diniz  1   2   3   4   5 , Elisa Weiss  1   2 , Andreas Steiner  1   2 , Silvija Tokic  6 , Corina T Madreiter-Sokolowski  7 , Susana P Pereira  3   4   8 , Ursula Hiden  1   2
Affiliations
Review

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Azra Kulovic-Sissawo et al. Biology (Basel). .

Abstract

Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative diseases, and it contributes significantly to the global health burden. Recent research indicates a link between cardiovascular risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, and endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are recruited into the vessel wall to maintain appropriate endothelial function, repair, and angiogenesis. After attachment, EPCs differentiate into mature endothelial cells (ECs). Like ECs, EPCs are also susceptible to CVRFs, including metabolic dysfunction and chronic inflammation. Therefore, mitochondrial dysfunction of EPCs may have long-term effects on the function of the mature ECs into which EPCs differentiate, particularly in the presence of endothelial damage. However, a link between CVRFs and impaired mitochondrial function in EPCs has hardly been investigated. In this review, we aim to consolidate existing knowledge on the development of mitochondrial and endothelial dysfunction in the vascular endothelium, place it in the context of recent studies investigating the consequences of CVRFs on EPCs, and discuss the role of mitochondrial dysfunction. Thus, we aim to gain a comprehensive understanding of mechanisms involved in EPC deterioration in relation to CVRFs and address potential therapeutic interventions targeting mitochondrial health to promote endothelial function.

Keywords: cardiovascular disease; cardiovascular risk factors; endothelial dysfunction; endothelial progenitor cells; mitochondrial dysfunction; neurodegenerative disorders; reactive oxygen species.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The interplay between metabolism, inflammation, reactive oxygen species, and mitochondrial dysfunction in the development of endothelial dysfunction and cardiovascular disease. Arrows indicate the directionality and stimulation of the respective processes. Influences that represent cardiovascular risk factors (CVRFs), i.e., nutrient excess and inflammation, are marked with yellow flashes. AGE: advanced glycation end products; CVD: cardiovascular disease; EC: endothelial cell; eNOS: endothelial nitric oxide synthase; mt: mitochondrial; NO: nitric oxide; NOX: NADPH oxidases; ROS: reactive oxygen species; XDH: xanthine dehydrogenase; XO: xanthine oxidase. The figure was created using BioRender.com, accessed on 22 January 2024.
Figure 2
Figure 2
Characteristics of healthy and dysfunctional endothelia and the role of endothelial progenitor cells in repair. Cardiovascular risk factors (CVRFs) disturb normal endothelial function and promote an activated endothelial cell phenotype. A dysfunctional endothelium is accompanied by oxidative stress with increased reactive oxygen species (ROS), inflammation, and reduced nitric oxide (NO) bioavailability. Under healthy conditions, circulating endothelial progenitor cells (EPCs) support, as endothelial colony-forming cells (ECFCs), endothelial repair and recovery. However, it is unclear how CVRFs affect ECFC efficacy and whether the cells remain able to complete repair and restore the endothelium. The figure was created using BioRender.com, accessed on 22 January 2024.
Figure 3
Figure 3
Mitochondria play a decisive role in shaping healthy vs. dysfunctional endothelial phenotypes. Cardiovascular risk factors (CVRFs) trigger detrimental mitochondrial impairment and dysfunction. In this context, impaired or damaged mitochondria discharge reactive oxygen species (mtROS) and mitochondrial-damage-associated molecular patterns (mtDAMPs) into the cytoplasm, which are degraded in the NLRP3 inflammasome. Mitochondrial dynamics shift towards increased fission. Mitophagy, a cellular process that involves the selective removal of damaged or dysfunctional mitochondria, emerges as a guardian of endothelial homeostasis. This process takes on the role of an athero-protective sentinel, as it systematically rids the endothelium of compromised mitochondria, thus safeguarding against the progression of atherosclerosis. Disruption of mitochondrial function and dynamics can pave the way for the onset of endothelial dysfunction and diseases. The figure was created using BioRender.com, accessed on 22 January 2024.
Figure 4
Figure 4
Exposure of endothelial progenitor cells to cardiovascular risk factors disturbs mitochondrial function in the differentiated endothelial cells. Exposure of circulating endothelial progenitor cells (EPCs) and progenitor cells in the bone marrow to cardiovascular risk factors (CVRFs) modulates their mitochondrial function in the long term. Thus, after recruiting the progenitors to the vascular wall, the differentiated endothelial cells remain with dysfunctional mitochondria, elevated reactive oxygen species (ROS) production, reduced mitochondrial membrane potential (MMP), and increased cytokine release. The figure was created using BioRender.com, accessed on 22 January 2024.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Koenig W. Low-Grade Inflammation Modifies Cardiovascular Risk Even at Very Low LDL-C Levels: Are We Aiming for a Dual Target Concept? Circulation. 2018;138:150–153. doi: 10.1161/CIRCULATIONAHA.118.035107. - DOI - PubMed
    1. Rodgers J.L., Jones J., Bolleddu S.I., Vanthenapalli S., Rodgers L.E., Shah K., Karia K., Panguluri S.K. Cardiovascular Risks Associated with Gender and Aging. J. Cardiovasc. Dev. Dis. 2019;6:19. doi: 10.3390/jcdd6020019. - DOI - PMC - PubMed
    1. Benincasa G., Coscioni E., Napoli C. Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention. Biochem. Pharmacol. 2022;202:115108. doi: 10.1016/j.bcp.2022.115108. - DOI - PubMed
    1. Incalza M.A., D’Oria R., Natalicchio A., Perrini S., Laviola L., Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul. Pharmacol. 2018;100:1–19. doi: 10.1016/j.vph.2017.05.005. - DOI - PubMed
    1. Rajendran P., Rengarajan T., Thangavel J., Nishigaki Y., Sakthisekaran D., Sethi G., Nishigaki I. The vascular endothelium and human diseases. Int. J. Biol. Sci. 2013;9:1057–1069. doi: 10.7150/ijbs.7502. - DOI - PMC - PubMed

LinkOut - more resources

-