Vascular Calcification

Background and aimsThe large-scale, randomized ILUMIEN IV trial was examined to determine whether procedural guidance with optical coherence tomography (OCT) during percutaneous coronary intervention (PCI) of angiographically calcified lesions improves outcomes.MethodsPatients with a single PCI target lesion were included in the present analysis. The presence of none, mild, moderate or severe lesion calcification was determined by an angiographic core laboratory. The primary imaging endpoint was the post-PCI minimal stent area (MSA) assessed by OCT. The primary clinical endpoint was 2-year target-vessel failure (TVF), a composite of cardiac death, target-vessel myocardial infarction (TV-MI), or ischaemia-driven target-vessel revascularization.ResultsIn the overall population (n = 2114), there was a significant interaction between the effect of randomization to OCT guidance vs angiography guidance in lesions with moderate/severe calcification (n = 1082) vs no/mild calcification (n = 1032) on the 2-year rate of TVF (Pinteraction = .01). The post-PCI MSA in moderately and severely calcified lesions was larger with OCT guidance (n = 544) compared with angiography guidance (n = 538) (5.57 ± 1.86 mm2 vs 5.33 ± 1.78 mm2; P = .03). In the moderate/severe calcified lesion cohort, TVF within 2 years occurred in 35 patients with OCT guidance and in 51 patients with angiography guidance (6.8% vs 9.7%; adjusted hazard ratio [aHR] 0.62; 95% confidence interval [CI] 0.40-0.96), whereas there was no significant difference in TVF in the no/mild calcified lesion cohort (7.7% vs 5.2%; aHR 1.48; 95% CI 0.90-2.44) (Pinteraction = .01). In moderately/severely calcified lesions, OCT-guided PCI also reduced the 2-year rates of serious major adverse cardiac events (2.8% vs 4.7%; aHR 0.49; 95% CI 0.25-0.95; P = .03), TV-MI (1.9% vs 4.0%; aHR 0.36; 95% CI 0.17-0.79; P = .01), and stent thrombosis (0.2% vs 1.5%; aHR 0.11; 95% CI 0.01-0.89; P = .04) compared with angiography-guided PCI.ConclusionsIn the ILUMIEN IV trial, OCT-guided PCI in patients with angiographically determined moderately or severely calcified lesions reduced the 2-year rate of TVF compared with angiography-guided PCI, an effect that was not seen in patients with lesions with no or mild angiographic calcium.

Vascular diseases present a significant threat to human health worldwide. Atherosclerosis is the most prevalent vascular disease, accounting for the majority of morbidity and mortality globally. Vascular calcification is a dynamic pathological process underlying the development of atherosclerotic plaques and involves the phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic cells. Specifically, the phenotypic switch in VSMCs often involves modifications in gene expression due to epigenetic changes, including DNA methylation, histone modification, and non-coding RNAs. Understanding the role of these epigenetic changes in regulating the pathophysiology of vascular calcification, along with the proteins and pathways that mediate these changes, will aid in identifying new therapeutic candidates to enhance vascular health. This review discusses a comprehensive range of epigenetic modifications and their implications for vascular health and the development of vascular calcification.

Background and Objectives: Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those on hemodialysis. Once considered a passive process, VC is now recognized as an active, cell-mediated pathology influenced by mineral dysregulation, chronic inflammation, and oxidative stress. This review aims to synthesize current evidence on the underlying mechanisms of VC in CKD and hemodialysis, with particular focus on emerging biomarkers and therapeutic implications. Materials and Methods: A structured narrative review was conducted by searching PubMed, Web of Science, ScienceDirect, and Google Scholar. The final search was completed on 29 August 2025. A total of 1326 articles were initially retrieved, of which 65 met the inclusion criteria and were analyzed. Studies addressing VC mechanisms, the bone-vascular axis, mineral metabolism, vitamin K-dependent proteins, and biomarkers such as matrix Gla protein (MGP), osteocalcin (OC), and intact parathyroid hormone (iPTH) were included. Results: VC in CKD arises from phenotypic transformation of vascular smooth muscle cells, vesicle-mediated calcification, oxidative stress, and impaired activity of endogenous calcification inhibitors. Disruption of the fibroblast growth factor 23 (FGF23)-Klotho axis and secondary hyperparathyroidism further exacerbate vascular pathology. Among emerging biomarkers, dp-ucMGP reflects vitamin K deficiency and correlates with calcification burden, while OC and iPTH provide insight into bone-vascular crosstalk and mineral turnover. However, biomarker interpretation is limited by assay variability, renal clearance, and clinical heterogeneity. Conclusions: VC in CKD represents a complex process driven by systemic and cellular dysregulation. While biomarkers such as dp-ucMGP, OC, and iPTH offer mechanistic insights and prognostic potential, further validation is required for clinical application. A multimarker approach, combined with individualized management of mineral metabolism, may improve risk stratification and therapeutic targeting in this high-risk population.

Key pointsA high-phosphate and low-protein combination diet induced medial artery calcification, cutaneous vascular calcification, and kidney fibrosis in CKD mice. p38 mitogen-activated protein kinase signaling was highly activated in CKD mice fed a high-phosphate and low-protein diet. Pharmacologic p38 mitogen-activated protein kinase inhibition reduced vascular calcification and kidney fibrosis, suggesting a novel treatment for patients with CKD.BackgroundMedial artery calcification and cutaneous arteriolar calcification are prevalent in patients with CKD and are strongly associated with higher morbidity and mortality. Current experimental CKD models, however, often fail to fully replicate the patterns of medial artery calcification and cutaneous arteriolar calcification, limiting our ability to elucidate their underlying molecular pathways. Developing a reliable experimental model for CKD-associated calcification and using it to identify therapeutic targets is essential for advancing treatment strategies for these vascular complications. In this study, we used a novel strategy that incorporated a high-phosphate and low-protein (HPi-Lp) diet to promote medial artery and cutaneous vascular calcification in CKD mice.MethodsMice underwent five-sixths (5/6) nephrectomy and were then fed various diets. Vascular calcification was assessed using micro-computed tomography scans, Alizarin Red staining, Von Kossa staining, and calcium assays. Kidney impairment and fibrosis were also evaluated. RNA sequencing analysis was performed to identify key molecular pathways. The pharmacologic inhibitor SB203580 was used to determine the significance of p38 mitogen-activated protein kinase (MAPK) signaling in vivo .ResultsThe HPi-Lp diet markedly induced both medial artery and cutaneous vascular calcification in 5/6 nephrectomized mice while exacerbating kidney dysfunction and fibrosis. The p38 MAPK signaling was specifically highly activated. Pharmacologic inhibition of p38 MAPK signaling significantly reduced medial artery and cutaneous vascular calcification as well as associated kidney fibrosis.ConclusionsThe 5/6 nephrectomy CKD mouse model combined with a HPi-Lp diet effectively replicated medial artery and cutaneous arteriolar calcification.