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.

Tumour cells enhance their survival and proliferation through autocrine and paracrine signalling, thereby facilitating tumour progression. Sustained growth requires the formation of new blood vessels, making angiogenesis a major therapeutic target. Concurrently, tumour development involves metabolic reprogramming to support uncontrolled proliferation. While the role of tumour metabolism in immune regulation has been widely studied, its contribution to angiogenesis remains less understood. To summarize current knowledge on how tumour-driven lipid metabolic reprogramming influences angiogenesis within the tumour microenvironment (TME) and to identify potential therapeutic opportunities. We reviewed recent studies focusing on the intersection between tumour lipid metabolism and angiogenesis, integrating findings from experimental and translational research. Emerging evidence indicates that lipid metabolic alterations in tumour cells modulate endothelial function, vascular remodelling, and pro-angiogenic signalling pathways. These changes reshape the angiogenic landscape of the TME, contributing to tumour progression and therapy resistance. Understanding the interplay between lipid metabolism and angiogenesis may uncover novel therapeutic vulnerabilities. Targeting metabolic reprogramming in the TME could provide new avenues for anti-angiogenic strategies and improve patient outcomes.

Atherosclerosis is a chronic inflammatory disease driven by metabolic disorders, and macrophages play a central role in their occurrence and development. Macrophages are not static; their functional polarization and fate decisions are highly regulated by metabolic signals from the microenvironment, a process known as metabolic reprogramming. This review systematically reviews the latest progress in the metabolic reprogramming of glucose, lipids, and mitochondria in atherosclerosis, focusing on how key metabolites such as glycolysis, pentose phosphate pathway, cholesterol/sphingolipid metabolism, gut microbiota derivatives, and oxaloacetate dynamically regulate the inflammatory phenotype, foam cell formation, and immune response of macrophages. This review also delves into new concepts such as trained immunity and analyzes the therapeutic potential of targeting these metabolic pathways, aiming to comprehensively reveal the core role of metabolic‐immune cross‐talk in atherosclerosis and provide a theoretical basis for developing new strategies for diagnosing and treating atherosclerosis based on macrophage metabolic reprogramming.

BACKGROUND:Diabetes is one of the most common and fastest-growing diseases worldwide, and diabetic atherosclerotic calcification is a frequent and fatal complication, the underlying mechanisms of which remain unclear. In this study, we investigated the mechanism by which HNRNPC regulates diabetic vascular calcification. METHODS:We retrieved datasets GSE211722, GSE84012, and GSE74755 from the GEO database and performed probe-to-gene name conversion. Based on expression profile data and aortic transcriptomic data from diabetic and non-diabetic mice, RNA m6A methylation-related regulatory genes were screened, and violin plots and heatmaps were generated accordingly. Differential genes identified from the expression profiles and experimental groups were subjected to intersection analysis to ultimately identify the target gene. We also enrolled coronary heart disease patients meeting predefined inclusion criteria to analyze the correlation between coronary artery calcium scores and serum HNRNPC levels. Subsequently, through transcription factor prediction and validation using single-cell transcriptomic data from the anterior tibial arteries of diabetic amputation patients, transcription factors of HNRNPC were identified. The role of HNRNPC in diabetic atherosclerotic calcification was further investigated by establishing an in vitro model of smooth muscle cells under high-glucose conditions and an in vivo model of diabetic atherosclerotic calcification in ApoE-/- mice. RESULTS:Analysis of GEO datasets and diabetic mouse transcriptomic data identified HNRNPC as the only overlapping differentially expressed m6A methylation regulatory gene from both sources. Clinical investigations revealed that serum HNRNPC levels and coronary artery calcium scores were elevated in diabetic patients and exhibited a positive correlation. In vitro and in vivo experiments demonstrated that inhibiting HNRNPC reduced the expression of the osteogenic marker RUNX2 and decreased calcium deposition, whereas HNRNPC overexpression promoted calcification. By integrating bioinformatics analysis with cellular (MOVAS) and animal (ApoE-/- mice) models, the transcription factor YY1 was revealed to play a pivotal role in vascular calcification. During calcification, YY1 expression was upregulated, and it directly bound to and activated the HNRNPC promoter, thereby enhancing HNRNPC transcription. Silencing YY1 significantly suppressed calcium deposition and osteogenic marker expression, whereas overexpressing HNRNPC reversed this effect, confirming that YY1 drives smooth muscle cell calcification by regulating HNRNPC expression. CONCLUSION:We demonstrate a previously unrecognized role of HNRNPC as a key driver of diabetic atherosclerotic calcification. Specifically, the transcription factor YY1 promotes calcification by mediating HNRNPC's function.

Vascular calcification (VC) is a complex pathological process, which is closely related to chronic kidney disease, atherosclerosis, diabetes and aging. This phenomenon is mainly driven by the convergence of cellular and molecular molecular mechanisms, including osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), persistent oxidative stress, extracellular vesicle-mediated calcification, and activation of multiple cross-signaling signaling pathways. The multifaceted evidence emphasizes the key role of VSMCs cytoskeleton remodeling in the progression of VC, and establishes a significant link between cytoskeleton dynamics and calcification initiation, which has potential predictive value under specific conditions. This article reviews the factors affecting the remodeling and stability of VSMCs cytoskeleton, focusing on their effects on VSMCs transdifferentiation and calcification. Finally, we highlighted the role of cytoskeleton in the process of cardiovascular calcification, explored strategies for mediating calcification, and proposed potential directions for future research.

BACKGROUND AND PURPOSE:Diabetes can lead to serious complications and significantly increase the risk of myocardial infarction. This study aimed to elucidate the role of STING1 in angiogenesis after diabetic myocardial infarction. METHODS:We established a diabetic myocardial infarction model in wild-type and Sting1-/- mice. Myocardial structure, fibrosis, and cardiac function were assessed via histological analysis and echocardiography. In vitro, primary cardiac microvascular endothelial cells were transfected with siRNA targeting STING1 to evaluate their proliferation, migration, tube formation ability, and apoptosis. Pathway enrichment analysis was performed using Gene Set Enrichment Analysis. RESULTS:Wild-type diabetic myocardial infarction mice exhibited disordered myocardial structure, increased fibrosis, and impaired cardiac function. In contrast, Sting1-/- mice exhibited restored cardiac function and significantly enhanced angiogenesis. At the cellular level, STING1 inhibition alleviated endothelial cell damage, promoted proliferation, migration, and tube formation, and reduced apoptosis. GSEA further indicated significant enrichment of the Wnt, MAPK, TGF-β, Tight junction, and PI3K-Akt signaling pathways in this process. CONCLUSION:These findings demonstrate that inhibiting STING1 promotes the recovery of cardiac structure and function after diabetic myocardial infarction by facilitating angiogenesis. This protective effect may involve the regulation of the Wnt, MAPK, TGF-β, Tight junction, and PI3K-Akt signaling pathways.

Vascular calcification (VC) represents a pathological hallmark of diseases such as chronic kidney disease (CKD) and diabetes, driven by the dysregulated activity of matrix vesicles (MVs). Under physiological conditions, MVs orchestrate skeletal mineralization, but in pathological microenvironments characterized by hyperphosphatemia and inflammation, they initiate and propagate ectopic calcification within the vascular wall. This review systematically examines the dual role of MVs—as both drivers of pathology and potential therapeutic vectors. We detail two strategic approaches: engineering MVs into targeted delivery systems for anti-calcific agents, and developing selective inhibitors against key molecular regulators of the MV lifecycle. By integrating mechanistic insights with translational perspectives, we propose an innovative “mechanism–biomarker–drug–delivery” framework that advances the development of precise, MV-based therapeutics. This work not only clarifies the pivotal role of MVs in VC but also charts a promising pathway toward clinically viable interventions, highlighting MVs as central targets in the future of precision medicine for VC. λ Matrix vesicles act as “mineralization microfactories” that initiate pathological calcification in the vascular wall by concentrating calcium and phosphate. λ Matrix Vesicles drive disease progression by delivering signaling molecules (e.g., miRNAs) and fueling a “bone-vascular” vicious cycle. λ The inhibition of key matrix vesicle components such as PHOSPHO1 and sortilin offers a therapeutic strategy for suppressing pathological mineralization. λ We propose an integrated “mechanism–biomarker–drug–delivery” framework, paving the way for precision medicine in vascular calcification.

Background: Vascular calcification is a major cause of adverse outcomes of acute cardiovascular events in diabetic patients. However, the effective therapeutic target for diabetic atherosclerotic calcification remains unclear. Branched-chain amino acid transaminase 2 (BCAT2), a key rate-limiting enzyme of branched-chain amino acid (BCAA) catabolism, may play a potential role in the development of diabetic complications. This study aimed to elucidate the role of BCAT2 in diabetic atherosclerotic calcification. Methods: Airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was employed to investigate the spatial distribution of metabolites in frozen arterial sections obtained from diabetic foot amputations. Single-cell RNA sequencing datasets from arteries of diabetic foot amputations were used to identify the expression of metabolic enzymes in the BCAA catabolism. ApoE knockout mice with specific deletion of BCAT2 in vascular smooth muscle cells (VSMCs) were generated, and a diabetic atherosclerotic calcification model was established to evaluate the impact of BCAT2 in diabetic atherosclerotic calcification. Further, the gene regulatory mechanisms of BCAT2 in diabetic atherosclerotic calcification were investigated. Results: BCAA catabolism was enhanced in the calcified anterior tibial arteries from diabetic foot amputation revealed by spatial metabolomics. Furthermore, BCAT2 was found to be up-regulated in VSMCs of calcified anterior tibial arteries from diabetic foot amputation by single-cell transcriptomics. Notably, VSMC-specific BCAT2 deficiency attenuated diabetic atherosclerotic calcification without sex bias. Further experiments revealed that branched-chain α-ketoacids (BCKA) supplement, especially α-keto-β-methylvaleric acid (KMV) and α-ketoisovaleric acid (KIV), promoted osteogenic differentiation of VSMCs and diabetic atherosclerotic calcification. Mechanistically, VSMC-specific BCAT2 deficiency suppressed the generation of BCKA-derived propionyl-CoA, mitigating histone propionylation at the promoter of RUNX2, and thereby osteogenic differentiation of VSMCs and diabetic atherosclerotic calcification. Conclusions: Our study demonstrates a previously unrecognized role of BCAA catabolism in diabetic atherosclerotic calcification and further delineates that the BCAT2–BCKA axis contributes to the osteoblastic differentiation of VSMCs by epigenetically modulating RUNX2 expression via histone propionylation.

INTRODUCTION:Calcified aortic valve disease (CAVD) imposes a severe global health burden, and there is currently no effective pharmacotherapy, which urgently requires a new understanding of pathophysiology to guide treatment. AREAS COVERED:This review systematically evaluates the epidemiological association and common mechanistic pathways between metabolic diseases and aortic valve calcification (AVC) through the proposed 'calcification-metabolic axis' framework. We conducted a comprehensive literature search, covering the PubMed database up to December 2025, with a focus on studies related to CAVD, metabolism, inflammation, and calcification signaling. EXPERT OPINION:Future management strategies must transition toward early, multi-disease co-governance strategies. At the same time, targeted drugs will be developed for specific pathways on this axis, surpassing the current treatment status of relying solely on valve replacement surgery.

Vascular calcification (VC), a pathological hallmark of advanced atherosclerosis, exerts a profound impact on arterial stiffness and the incidence of cardiovascular disease. Its development involves not only actively regulated biological processes but also passive mineral deposition and is particularly prevalent in patients with diabetes, chronic kidney disease, and endocrine disorders. Although conventional therapies—such as phosphate binders, calcium channel blockers, bisphosphonates, and endovascular interventions—form the current clinical foundation, they remain inadequate for preventing early VC or reversing established lesions. This review systematically summarizes advances in both standard strategies and emerging therapies. Recent studies have highlighted several breakthrough approaches: nanotechnology-based delivery systems, optimized agents such as SNF472 and GLP-1 receptor agonists, and bioactive constituents from traditional Chinese medicine (e.g., ginsenosides, chelerythrine), all of which target distinct calcification pathways. In addition, dietary interventions and lifestyle modification show preventive value. Progress in multi-omics technologies continues to uncover new molecular mechanisms and therapeutic targets, guiding precision medicine. By integrating mechanistic insights with novel therapeutic paradigms, this review aims to facilitate the development of personalized management strategies and ultimately improve cardiovascular outcomes in high-risk populations. Active/passive hydroxyapatite underlies VC; inflammation and iron imbalance drive. VSMC transdifferentiation/apoptosis are central; BMP, Wnt, and NF-κB intersect. Emerging options: nanomedicine, SNF472, GLP-1RAs, and pyrophosphate target VC. Nutrients (vitamin K/D, Mg, Zn) plus iron modulation, diet and exercise aid control. Multi-omics and precision delivery reveal targets; severe lesions may benefit from IVL. VC: Mechanisms, Risk Factors, and Innovative Treatment Strategies: This figure summarizes VC from mechanisms to treatments.

BACKGROUND:Albumin-to-neutrophil-lymphocyte ratio (ANLR) is a novel composite biomarker integrating nutritional and inflammatory status. However, its prognostic value for mortality in the general population remains unclear. This study aimed to evaluate the predictive utility of ANLR for all-cause and cardiovascular mortality. METHODS:This study included 36 628 adults from the National Health and Nutrition Examination Survey 2003-2018. Mortality details were ascertained from the National Death Index. The relationship between ANLR and all-cause and cardiovascular mortality was verified using restricted cubic spline (RCS), weighted Cox proportional hazards model, subgroup analysis and time-dependent receiver operating characteristic curve (ROC). RESULTS:RCS analysis revealed an L-shaped ANLR-mortality relationship with an inflection point at 2.19. Below this threshold, each 0.1-unit ANLR increase was associated with 5.0% lower all-cause mortality (HR 0.95, 95% CI 0.94-0.96) and 6.0% lower cardiovascular mortality (HR 0.94, 95% CI 0.92-0.96). Participants were stratified into higher (> 1.23) and lower (≤ 1.23) ANLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher ANLR had a significantly reduced risk of all-cause (HR 0.57, 95% CI 0.53-0.62) and cardiovascular mortality (HR 0.55, 95% CI 0.47-0.65). Results were consistent across subgroups. Time-dependent ROC analysis confirmed moderate predictive ability over 1-7 years, with area under the curve values of 0.667-0.708 for all-cause and 0.690-0.703 for cardiovascular mortality. CONCLUSION:Elevated ANLR is associated with reduced mortality risk, though non-linearly. Clinical attention to albumin supplementation and maintaining appropriate neutrophil-to-lymphocyte ratio levels may be warranted in high-risk populations.

AIMS:Microcalcification increases the vulnerability of plaques and has become an important driver of acute cardiovascular events in diabetic patients. However, the regulatory mechanisms remain unclear. DJ-1, a multifunctional protein, may play a potential role in the development of diabetic complications. Therefore, this study aims to explore the relationship between DJ-1 and microcalcification in diabetic plaques and investigate the mechanisms. METHODS AND RESULTS:The regulatory relationship between DJ-1 and diabetic vascular microcalcification was determined in anterior tibial arteries from diabetic foot amputated patients, a diabetic apolipoprotein E-deficient (ApoE-/-) mouse model, and a vascular smooth muscle cell (VSMC) model. The ubiquitination and acetylation levels of DJ-1 were detected, and the acetylation-ubiquitination crosstalk was explored. Then, the regulatory effects of DJ-1 on receptor for advanced glycation end products (RAGE) were clarified. Further, the role of DJ-1 in collagen-matrix vesicles (MVs) interaction in diabetic microenvironment was observed. The collagen interacting surface protein of MVs was verified with proteomics and the biomimetic MVs model. In clinical samples, the number of microcalcification nodules in anterior tibial artery plaques was negatively correlated with DJ-1 expression. In diabetic ApoE-/- mice and VSMCs models, knocking down DJ-1 significantly increased the number of microcalcified nodules. N-acetyltransferase 10 (NAT10) was an acetyltransferase of DJ-1. NAT10 could crosstalk the ubiquitination of DJ-1 and enhance the ubiquitination of DJ-1 by E3 ubiquitin ligase tripartite motif-containing protein 32 (TRIM32). Besides, the knockdown of DJ-1 activated signal transducer and activator of transcription 1 (STAT1), and then STAT1 could bind to RAGE promoter, thus up-regulating RAGE. Furthermore, the knockdown of DJ-1 significantly promoted collagen-MVs interaction in diabetic microenvironment. Milk fat globule epidermal growth factor 8 (MFGE8) may serve as a collagen-interacting protein. The coating of MFGE8 protein could increase the interaction between collagen and biomimetic MVs. CONCLUSION:In the diabetic microenvironment, DJ-1 was a protective factor for vascular microcalcification. NAT10- and TRIM32-mediated acetylation-ubiquitination crosstalk resulted in the degradation of DJ-1. The decrease of DJ-1 could activate DJ-1/STAT1/RAGE microcalcification signal. Further, under the stimulation of DJ-1-mediated microcalcification signal, VSMCs released MVs with high abundance of MFGE8. MFGE8 promoted collagen-MVs interaction and finally accelerated the formation of microcalcification.

Compensatory angiogenesis is critical for preserving left ventricular function after myocardial infarction; however, this process is severely impaired in diabetes, exacerbating adverse outcomes in diabetic myocardial infarction (DMI). This study employed liquid chromatography-tandem mass spectrometry to identify lactylated proteins in the infarct border zone of DMI male mouse hearts. Our findings revealed that IDH2 is lactylated at lysine 272, enhancing its binding to Cav1 while inhibiting the Cav1-eNOS interaction. This modification promotes eNOS activity and facilitates the proliferation, migration, and angiogenesis of cardiac microvascular endothelial cells under high glucose and hypoxic conditions. In endothelial cell-specific IDH2-K272R knock-in male mice, the loss of K272 lactylation impairs cardiac function and exacerbates pathological remodeling due to disrupted angiogenesis. Additionally, ACAT1 and HDAC1 act as lactyltransferase and delactylase, respectively, utilizing intracellular lactate transported via MCT1 as a substrate for IDH2 lactylation. Furthermore, pharmacologic enhancement of IDH2 lactylation, as demonstrated by empagliflozin mitigating post-DMI injury, supports its potential as a therapeutic target for DMI.

Atherosclerosis is driven by the expansion of cholesterol-loaded foamy macrophages in the arterial intima. Single-cell RNA sequencing has recently revealed the transcriptional landscape of macrophages in these atherosclerotic plaques and uncovered a population of foamy cell-like myeloid cells expressing triggering receptor expressed on myeloid cells-2 (TREM2)-TREM2hi macrophages. Fundamental research has brought essential insight into the significance of TREM2 for foam macrophage survival and atherosclerosis progression, making TREM2 as a therapeutic target in atherosclerosis possible. This review retraces TREM2's winding route from pure knowledge to therapeutic interventions, as well as the potential feasibility of its clinical application for atherosclerosis.

Atherosclerotic cardiovascular and cerebrovascular diseases are the number one killer of human health. In view of the important role of mitochondria in the formation and evolution of atherosclerosis, our manuscript aims to comprehensively elaborate the relationship between mitochondria and the formation and evolution of atherosclerosis from the aspects of mitochondrial dynamics, mitochondria-organelle interaction (communication), mitochondria and cell death, mitochondria and vascular smooth muscle cell phenotypic switch, etc., which is combined with genome, transcriptome and proteome, in order to provide new ideas for the pathogenesis of atherosclerosis and the diagnosis and treatment of related diseases.

With the in-depth investigation of various diseases, angiogenesis has gained increasing attention. Among the contributing factors to angiogenesis research, endothelial epigenetics has emerged as an influential player. Endothelial epigenetic therapy exerts its regulatory effects on endothelial cells by controlling gene expression, RNA, and histone modification within these cells, which subsequently promotes or inhibits angiogenesis. As a result, this therapeutic approach offers potential strategies for disease treatment. The purpose of this review is to outline the pertinent mechanisms of endothelial cell epigenetics, encompassing glycolysis, lactation, amino acid metabolism, non-coding RNA, DNA methylation, histone modification, and their connections to specific diseases and clinical applications. We firmly believe that endothelial cell epigenetics has the potential to become an integral component of precision medicine therapy, unveiling novel therapeutic targets and providing new directions and opportunities for disease treatment. Graphical Abstract In recent years, with the deepening of people’s understanding of diseases, angiogenesis has been paid more and more attention. Endothelial cells, as the key cells in angiogenesis, play an important role in the field of angiogenesis research. Glycolysis, lactation, pentose phosphate pathway, amino acid metabolism, non-coding RNA, DNA methylation, histone modification, etc., all have an impact on endothelial cells and thus affect angiogenesis. Endothelial cell epigenetics is expected to become part of precision medicine treatments. Individual treatment plans can be implemented for patients, and precision medicine treatment strategies can be realized. Through epigenetic studies of endothelial cells, new drugs or therapeutic regimens can be developed for clinical application to reduce pain in patients and delay disease progression. Combined with other therapeutic strategies, it can control and guide the formation and reconstruction of blood vessels, and play different roles in different diseases such as diabetes, cardiovascular diseases, and tumors.

Vascular calcification (VC) is common in patients with advanced chronic kidney disease (CKD).A series of factors, such as calcium and phosphorus metabolism disorders, uremic toxin accumulation, inflammation and oxidative stress and cellular senescence, cause osteoblast-like differentiation of vascular smooth muscle cells, secretion of extracellular vesicles, and imbalance of calcium regulatory factors, which together promote the development of VC in CKD. Recent advances in epigenetics have provided better tools for the investigation of VC etiology and new approaches for finding more accurate biomarkers. These advances have not only deepened our understanding of the pathophysiological mechanisms of VC in CKD, but also provided valuable clues for the optimization of clinical predictors and the exploration of potential therapeutic targets. The aim of this article is to provide a comprehensive overview of the pathogenesis of CKD VC, especially the new advances made in recent years, including the various key factors mentioned above. Through the comprehensive analysis, we expect to provide a solid theoretical foundation and research direction for future studies targeting the specific mechanisms of CKD VC, the establishment of clinical predictive indicators and the development of potential therapeutic strategies.

BACKGROUND:Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. METHOD:Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. RESULT:We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. CONCLUSION:This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming.

Vascular calcification is an important pathological change in a variety of disease states such as atherosclerosis (AS), diabetes, chronic kidney disease (CKD), hypertension, and is a strong predictor of cardiovascular events. The distribution and location of calcification in different vessels may have different clinical effects and prognosis. Therefore, the study of high-risk sites of vascular calcification will help us to better understand the prevention, diagnosis and treatment of related diseases, as well as to evaluate the efficacy and prognosis. So far, although there are some studies on the sites with high incidence of vascular calcification, there is a lack of systematic sorting out the distribution and location of vascular calcification in humans. Based on this, relevant databases were searched, literatures were retrieved, analyzed and summarized, and the locations of high incidence of vascular calcification and their distribution characteristics, the relationship between high incidence of vascular calcification and hemodynamics, and the common detection methods of high incidence of vascular calcification were systematically described, hoping to provide help for clinical and research.