Unique fluoroalkyl substituents: is there life after CF(3)?

Vascular calcification (VC) is the abnormal deposition of calcium phosphate, primarily hydroxyapatite, within the vascular walls. It serves as a common pathophysiological mechanism underlying several diseases, including atherosclerosis, diabetes mellitus (DM), chronic kidney disease (CKD), and hypertension. VC is a major contributor to the high incidence and mortality rates of cardiovascular and cerebrovascular diseases (). DM is a systemic metabolic disorder resulting from the combined effects of genetic and environmental factors, characterized primarily by abnormally elevated blood glucose levels. This condition substantially increases the risk of complications, impairs quality of life, and increases mortality (). Existing clinical studies provide substantial evidence supporting a clear association between DM and VC (–). Mechanistically, mounting evidence suggests that several factors associated with metabolic syndrome (MetS) and linked to type 2 DM (T2DM) may promote VC. These factors include oxidative stress, endothelial dysfunction, dyslipidemia, mineral metabolism disturbances, and elevated synthesis of pro-inflammatory cytokines (). Recent studies suggest that under high glucose (HG) conditions induced by DM, disrupted extracellular pyrophosphate (PPi) metabolism, along with the action of extracellular vesicles via the circ_0008362/miR-1251-5p/Runx2 axis, promotes VC (, ). Uric acid (UA) is the end product of purine metabolism. At physiological concentrations, serum uric acid (SUA) plays a key role in combating oxidative stress, protecting against DNA damage, and scavenging free radicals (, ). However, excessively high SUA levels promote oxidative reactions that trigger vascular smooth muscle proliferation, endothelial dysfunction, and local tissue damage, contributing to conditions such as gout and cardiovascular disease (). Excessively low SUA levels may contribute to the development of conditions such as Alzheimer’s and Parkinson’s diseases (–). The current pooled prevalence of hyperuricemia in China is 16.4%, demonstrating a significant upward trend (). Basic research using animal and cellular models suggests that HUA inhibits osteoblast differentiation and proliferation both and , while promoting the osteoblast-like transdifferentiation of vascular smooth muscle cells (VSMCs), thereby increasing the risk of VC (). However, existing clinical evidence is mixed, and the clinical relevance of SUA levels to VC has not been conclusively established (–). In patients with T2DM, the association between SUA levels and VC also remains. In summary, to further explore the relationship between SUA and VC in patients with T2DM, this study conducted a follow-up investigation of hospitalized T2DM patients at the Central hospital of Dalian University of Technology from January 2010 to January 2023. The aim was to determine whether SUA is an independent risk factor for the development of VC.