Microcalcification: Effects on Atherosclerotic Vulnerable Plaques, Detection, and Therapeutic Perspectives

We aim to elucidate the formation mechanisms of microcalcification in atherosclerotic plaques, systematically clarify its heterogeneous effects on plaque vulnerability, and summarize the latest advances in microcalcification detection technologies and targeted therapeutic strategies.

Microcalcification plays a pivotal role in atherosclerotic plaque vulnerability. Key features of microcalcification (size: 5-65 μm, irregular/prolate spheroidal morphology, h/D <0.4 spacing, and fibrous cap localization aligned with tensile axes) amplify local stress and increase plaque rupture risk. Recent studies have developed novel models to simulate the presence of microcalcifications in plaques and focused on investigating the effects of microcalcifications on collagen fibers and plaque constituent cells. Current detection technologies, such as ¹⁸F-NaF PET/CT, are capable of detecting vascular microcalcifications while performing risk stratification for atherosclerotic plaques. Hydroxyapatite mineralization and nucleation represent the initial process of microcalcification formation. Drugs targeting this process, namely SNF472 and bisphosphonates, have demonstrated excellent efficacy and safety in recent clinical trials. The impact of microcalcification on atherosclerotic plaque vulnerability is determined by its size, morphology, spacing, and location. Micro-CT, optical coherence tomography, and ¹⁸F-NaF PET/CT each have their own advantages in the detection of microcalcifications. Among them, ¹⁸F-NaF PET/CT has been used as a biomarker for microcalcification activity and is capable of identifying high-risk plaques. Drugs targeting hydroxyapatite nucleation, such as SNF472 and bisphosphonates, have made considerable progress in the treatment of vascular calcification, yet further clinical translational trials are still needed to verify their efficacy.