title: Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient.
abstract: Recent evidence has shown that 346million people in the world have diabetes mellitus (DM); this number will increase to 439million by 2030. In addition, current data indicate an increase in DM cases in the population between 40 and 59years of age. Diabetes is associated with the development of micro- and macro-vascular complications, derived from chronic hyperglycemia on the endothelium. Some reports demonstrate that people in a prediabetic state have a major risk of developing early endothelial dysfunction (ED). Today, it is accepted that individuals considered as prediabetic patients are in a pro-inflammatory state associated with endothelial and mitochondrial dysfunction. It is important to mention that impaired mitochondrial functionality has been linked to endothelial apoptosis and release of mitochondrial DNA (mtDNA) in patients with sepsis, cardiac disease, or atherosclerosis. This free mtDNA could promote ED, as well as other side effects on the vascular system through the activation of the toll-like receptor 9 (TLR9). TLR9 is expressed in different cell types (e.g., T or B lymphocytes, mastocytes, and epithelial and endothelial cells). It is localized intracellularly and recognizes non-methylated dinucleotides of viral, bacterial, and mitochondrial DNA. Recently, it has been reported that TLR9 is associated with the pathogenesis of lupus erythematosus, rheumatoid arthritis, and autoimmune diabetes. In this work, it is hypothesized that the increase in the levels of circulating mtDNA is the trigger of early ED in the prediabetic patient, and later on in the older patient with diabetes, through activation of the TLR9 present in the endothelium.
authors.affiliation: Department of Biochemistry, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Calz. de Tlalpan 4502, Col. Sección XVI, 14080 Mexico, D.F., Mexico, Mexico. Electronic address: nnooee@gmail.com.
authors.forename: Noé
authors.initials: N
authors.lastname: Alvarado-Vásquez
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000097:blood*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D042241:Early Diagnosis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D011236:Prediabetic State / Q000097:blood / Q000150:complications / Q000473:pathology; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D051217:Toll-Like Receptor 9
keywords: Diabetes mellitus type 2; Endothelial cell; Mitochondria; TLR9; Vascular system