Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities

Background: Mitochondria-derived peptides (MDPs) represent a recently discovered family of peptides encoded by short open reading frames (ORFs) found within mitochondrial genes. This group includes notable members including humanin (HN), mitochondrial ORF of the 12S rDNA type-c (MOTS-c), and small humanin-like peptides 1-6 (SHLP1-6). MDPs assume pivotal roles in the regulation of diverse cellular processes, encompassing apoptosis, inflammation, and oxidative stress, which are all essential for sustaining cellular viability and normal physiological functions. Their emerging significance extends beyond this, prompting a deeper exploration into their multifaceted roles and potential applications. Aim of review: This review aims to comprehensively explore the biogenesis, various types, and diverse functions of MDPs. It seeks to elucidate the central roles and underlying mechanisms by which MDPs participate in the onset and development of cardiovascular diseases (CVDs), bridging the connections between cell apoptosis, inflammation, and oxidative stress. Furthermore, the review highlights recent advancements in clinical research related to the utilization of MDPs in CVD diagnosis and treatment. Key scientific concepts of review: MDPs levels are diminished with aging and in the presence of CVDs, rendering them potential new indicators for the diagnosis of CVDs. Also, MDPs may represent a novel and promising strategy for CVD therapy. In this review, we delve into the biogenesis, various types, and diverse functions of MDPs. We aim to shed light on the pivotal roles and the underlying mechanisms through which MDPs contribute to the onset and advancement of CVDs connecting cell apoptosis, inflammation, and oxidative stress. We also provide insights into the current advancements in clinical research related to the utilization of MDPs in the treatment of CVDs. This review may provide valuable information with MDPs for CVD diagnosis and treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license.