Mitochondrial-Derived Peptides as Targets for Cardiovascular Disease Therapies

This review takes a look at a number of peptides related to mitochondrial function, and which are thought to potentially provide therapeutic benefit. Some are interesting in the context of aging. As is the case for most peptides with enough scientific literature to justify a review paper, availability and use is somewhat ahead of the science. Peptide manufacture is easy enough and cheap enough that most studied peptides can be purchased from established manufacturers. That certainly doesn't mean that they are in fact useful at the end of the day! This marketplace is very much like the supplement marketplace in that respect: there is a great deal more marketing than there is truth and robust evidence of benefits. That a mechanism exists, and connects to aspects of aging, such as mitochondrial dysfunction, is no guarantee that manipulating it will have a large enough effect to matter.

Mitochondria-derived peptides (MPDs) are a class of recently identified peptides, which are found within other known mitochondrial genes and encoded by small open reading frames (ORFs). The first MDP, Humanin (HN), was discovered in 2001 in patients with Alzheimer's disease and described as a neuroprotective peptide with a high therapeutic potential for neurodegenerative diseases. After HN, two other types of MDPs were discovered: mitochondrial ORF of the 12S rDNA type-c (MOTS-c) and small Humanin-like peptide, 1 to 6 (SHLP1-6).

MDPs are widely presented in different tissues, such as the kidney, skeletal muscle, colon, vascular wall, and heart. MDPs are released into the body via paracrine and endocrine pathways and have diverse functions as cytoprotective agents, such as maintaining cell viability and mitochondrial function under stress, are involved in cellular metabolism and cell survival and act in response to inflammation and oxidative stress. Recently, the role of MDPs was highlighted for many senescence and ageing-associated diseases, chronic inflammation diseases, cancer and neurodegenerative diseases, and retinal and fertility diseases.

In this review, we focus on the role of on MDPs as crucial peptides, modulating and regulating mitochondrial function and involved in pathological changes in cardiovascular disease via different molecular mechanisms. We also discuss the application of MDPs, modified MDPs and synthetic MDPs as uprising pharmaceutical tools for the treatment of cardiovascular diseases and other conditions. Further understanding the role of MDPs in various signalling pathways related to CVD would improve its medical significance and therapeutic potential.


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