Volume 170, May 2024, 106569Author links open overlay panel, , , , , , , , Abstract

Micro- and macrovascular complications frequently occur in patients with diabetes, with endothelial dysfunction playing a key role in the development and progression of the complications. For the early diagnosis and optimal treatment of vascular complications associated with diabetes, it is imperative to comprehend the cellular and molecular mechanisms governing the function of diabetic endothelial cells. Mitochondria function as crucial sensors of environmental and cellular stress regulating endothelial cell viability, structural integrity and function. Impaired mitochondrial quality control mechanisms and mitochondrial dysfunction are the main features of endothelial damage. Hence, targeted mitochondrial therapy is considered promising novel therapeutic options in vascular complications of diabetes. In this review, we focus on the mitochondrial functions in the vascular endothelial cells and the pathophysiological role of mitochondria in diabetic endothelial dysfunction, aiming to provide a reference for related drug development and clinical diagnosis and treatment.

Section snippetsPathology of diabetic endothelial dysfunction

The endothelium consists of a single-cell layer lining the inner surface of the vascular lumen and acts as a protective barrier separating the blood from the vessel wall (Sumpio et al., 2002). Endothelial cells are both a permeable barrier and a versatile paracrine and endocrine organ. Endothelial cells are involved in immune responses, coagulation, growth regulation, and production of extracellular matrix components, and secrete various vasoactive agents (vasodilators such as prostaglandin I2,

Mitochondria-induced diabetic endothelial dysfunction

Mitochondria are involved in ATP synthesis, cellular metabolic control and regulation of apoptosis (Cai et al., 2022). Mitochondria play a crucial role in energetic metabolism by upholding a delicate regulatory equilibrium between the concentration of Ca2+ and the production of NO. Furthermore, ROS, the toxic by-products of aerobic metabolism, are mainly produced by mitochondria (Liu et al., 2020, Jamar et al., 2017). Mitochondrial dysfunction severely affects tissue homeostasis. Mitochondrial

Conclusions and prospects

Vascular complications are the major cause of morbidity and mortality in T2DM, ultimately resulting in a decreased life expectancy for these individuals. Although drug therapy can provide reasonable glycemic control, many oral antidiabetic drugs available for the treatment of T2DM have failed to show a sustained reduction in cardiovascular mortality. Considering the intricate nature of the mechanisms associated with the onset and advancement of diseases, it is improbable that a solitary

Ethics approval and consent to participate

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (81904187), Capital Health Development Research Project (CD2020-4-4155), CACMS Outstanding Young Scientific and Technological Talents Program (ZZ13-YQ-026), CACMS Innovation Fund (CI2021A01601), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202001), Open Project of National Facility for Translational Medicine (TMSK-2021-407).

Acknowledgements

We would like to thank all the authors for their contribution to the realization of this manuscript.

Consent for publication

Not applicable.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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