Abstract:Endogenous bioactive small molecules are characterized by low molecular weight, high biological activity, low immunogenicity, and rapid synthesis and metabolism, play a pivotal role in maintaining vascular homeostasis.Vascular calcification (VC) is a abnormal deposition of calcium and phosphorus in the vessel wall. Endogenous bioactive small molecules such as cardiovascular bioactive peptides, adipokines and gaseous molecules participate in the process of VC through various mechanisms. This review summarises the advances in relationship between endogenous bioactive small molecules and the occurrence, development, and related mechanisms of VC.

Abstract:As a common complication of chronic kidney disease(CKD), vascular calcification(VC) significantly increases the incidence of CKD-complicated cardiovascular disease (CVD) and mortality. As chronic kidney disease advances and the glomerular filtration rate(GFT) declines, certain solutes, incapable of efficient filtration and elimination, amass within the body, coalescing into uremic toxins which instigate a spectrum of complications, ultimately intensifying mortality rates. Gut-derived uremic toxins(GUT), products of intestinal flora metabolizing and fermenting intestinal substances, significantly influence the trajectory and prognosis of CKD patients, exerting a pivotal role in the genesis of VC. Manipulating uremic toxin levels by modulating the host gut microbiota emerges as a potential means to prevent and manage VC. This discourse delves into elucidating the precise mechanisms through which various commonplace GUT—encompassing small molecules, macromolecules, and protein-bound toxins—impact the evolution of VC. This impact is predominantly observed through their modulation of the hosts inflammatory response, oxidative stress, and signaling pathways. These insights offer a potential avenue for the modulation of uremic toxin levels, positing a novel adjunctive therapeutic approach for managing VC.

Abstract:The gut microbiome actively regulates host immunity, digestive processes, and the function of the intestinal endocrine system. Additionally, it modulates host neural signal transmission and nutrient metabolism through metabolite generation. Vascular calcification involves the deposition of calcium phosphate in blood vessel walls, secondary to metabolic disorders such as chronic kidney disease, atherosclerosis, diabetes, and osteoporosis. Recent research spanning the past two decades has indicated a close correlation between shifts in the composition and functionality of the gut microbiota, along with its metabolites, and the onset of metabolic disease-related vascular calcification. This paper presents a comprehensive review of the roles and mechanisms of the gut microbiota in this context.

Abstract:Aim To investigate the effect of hydrogen sulfide on macrophage calcification and its underlying molecular mechanisms. Methods Oil red O staining was used to observe intracellular lipid accumulation, and von Kossa staining and atomic absorption spectroscopy were used for morphological and quantitative analysis of calcium deposition and intracellular calcium content in a mononuclear macrophage calcification model. Western blot and RT-PCR were used to detect the mRNA and protein expression of osteopontin (OPN) at different doses and treatment times of hydrogen sulfide.At the same time, Western blot was used to detect the expression changes of early growth response factor 1 (EGR1), endoplasmic reticulum stress-related markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78).Reactive oxygen species levels were evaluated by fluorescence probe staining, and the effect of hydrogen sulfide on macrophage calcification was evaluated by combining von Kossa staining and calcium ion fluorescence probe staining. The molecular mechanisms of hydrogen sulfide affecting macrophage calcification were explored by interfering with EGR1 expression and using endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA). Results Compared with oxidized low density lipoprotein (ox-LDL) group, β-glycerophosphate (β-GP)＋40 g/L ox-LDL group showed a significant increase in intracellular lipid accumulation, while hydrogen sulfide significantly inhibited macrophage calcification in a concentration- and time-dependent manner. Compared with the β-GP＋ox LDL group, the most significant effect was observed after incubation with 100 μ mol/L NaHS for 4 days. The hydrogen sulfide group showed a 66% decrease in intracellular calcium content (P＜0.01), a 71% decrease in intercellular calcium deposition (P＜0.01), and a 50% and 48% decrease in OPN mRNA and protein expression, respectively (P＜0.05). Hydrogen sulfide treatment upregulated the expression of EGR1 by 21%, while downregulating the expression of CHOP and GRP78 by 58% and 59%, respectively (P＜0.01). The endoplasmic reticulum stress inhibitor 4-PBA could downregulate OPN expression by 73% (P＜0.01), while interfering with EGR1 expression completely counteracts the inhibitory effect of hydrogen sulfide on OPN expression and calcium deposition (P＜0.01). Conclusion Hydrogen sulfide significantly inhibits macrophage calcification by upregulating EGR1 expression and suppressing endoplasmic reticulum stress.

Abstract:Aim To investigate the correlation between blood lipid level and the severity of coronary artery calcification (CAC) in peritoneal dialysis (PD) patients with chronic kidney disease (CKD). Methods 205 CKD patients treated with PD in our hospital from June 2018 to December 2021 were selected as the study subjects, according to the CAC scores, they were divided into calcified group (n＝152) and non-calcified group (n＝53), and the patients in calcified group were divided into mild calcification group (n＝61), moderate calcification group (n＝50), and severe calcification group (n＝41). The differences in clinical data and laboratory indicators were compared through univariate analysis. The restricted cubic spline fitting Logistic regression model was used to analyze the relationship between blood lipid levels and CAC. Multiple Logistic regression model was used to analyze the influencing factors, receiver operating characteristic (ROC) curve was drawn to explore the predictive value of blood lipid levels for the severity of CAC. Results Compared with the non-calcified group, the age, diabetes ratio, body mass index(BMI), triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDLC), and blood phosphorus levels increased significantly in the calcified group, the levels of uric acid(UA), high density lipoprotein cholesterol(HDLC), blood magnesium, and 25-hydroxyvitamin D3 (25-(OH)-VitD3) were significantly reduced (P＜0.05); Logistic regression showed that adjusted TC(OR=1.9,5%CI:1.56~2.10), TG(OR=2.3,5%CI:1.86~2.41), HDLC(OR=0.7,5%CI:0.42~0.84), LDLC(OR=2.1,5%CI:1.78~2.32) were still a risk factor for the occurrence of CAC after adjusting for age, diabetes and other factors, and as the levels of TG, TC, and LDLC increased, the levels of HDLC decreased, and their correlation effect values also increased correspondingly (Ptrend＜0.05). Compared with the mild calcification group, the age, TG, and TC of the moderate and severe calcification groups significantly increased, HDLC significantly decreased, UA significantly increased in the moderate calcification group, LDLC and blood phosphorus significantly increased in the severe calcification group, while blood magnesium and 25-(OH)-VitD3 significantly decreased; Compared with the moderate calcification group, the severe calcification group showed a significant increase in TC and LDLC, while UA and HDLC decreased significantly (all P＜0.05). And the multiple Logistic regression model showed that older age, higher levels of TG, TC, LDLC, and lower level of HDLC were independent risk factors for severe CAC in CKD patients after PD treatment (P＜0.05). Restrictive cubic spline regression analysis showed a significant correlation between blood lipid levels and the severity of CAC. ROC curve analysis showed that the AUC of TG, TC, HDLC, and LDLC combined detection was 0.897, with a sensitivity of 0.899, and a specificity of 0.826. This indicated that the predictive value of TG, TC, HDLC, and LDLC combined detection for the severity of CAC in CKD patients undergoing PD treatment was higher than any single indicator. Conclusion The increased levels of TG, TC, LDLC and decreased level of HDLC were significantly associated with the risk of CAC in CKD patients undergoing PD treatment, they were also involved in the occurrence and development of CAC, and their predictive value can be improved through joint examinations in clinical practice.

Abstract:Aim To investigate the factors influencing carotid artery calcification in patients with ischemic stroke and to construct a predictive model for columnar plots to provide reference for clinical formulation of prevention and control measures. Methods A total of 500 patients with ischemic stroke were randomly divided into modeling group (350 cases) and verification group (150 cases) according to a ratio of 7∶3, and the incidence of carotid artery calcification was analyzed. LASSO-Logistic regression equation was used to analyze the influencing factors of carotid artery calcification, and the prediction model of carotid artery calcification risk was built. Receiver operating characteristic (ROC) curve and calibration curve were used to analyze the nomogram to predict model differentiation and accuracy. Decision curve analysis (DCA) was drawn to evaluate the validity of the prediction model. Results In the modeling group, compared with those without carotid artery calcification, the age of those with carotid artery calcification increased by 17.87%, the proportion of smoking history increased by 32.69%, the level of fasting blood glucose increased by 22.47%, the level of glycated hemoglobin increased by 0.69%, and the level of low density lipoprotein cholesterol (LDLC) increased by 17.84%, the uric acid level increased by 22.42%, the high sensitivity C-reactive protein (hs-CRP) level increased by 40.31%, and the estimated glomerular filtration rate (eGFR) level decreased by 7.04%, with statistical significance (P＜0.05). In the verification group, compared with those without carotid artery calcification, the age of those with carotid artery calcification increased by 17.23%, the proportion of smoking history increased by 33.39%, the level of fasting blood glucose increased by 22.37%, the level of glycated hemoglobin increased by 0.75%, the level of LDLC increased by 17.96%, and the level of uric acid increased by 24.44%, hs-CRP level increased by 30.81%, eGFR level decreased by 6.46%, the difference was statistically significant (P＜0.05). In the modeling group and the verification group, the prediction models of carotid artery calcification were constructed based on the above factors, and the AUC for predicting carotid artery calcification was 0.953 and 0.972, respectively, which was accurate and clinically effective. Conclusion Increasing age, smoking history and increased fasting blood glucose, glycated hemoglobin, LDLC, uric acid and hs-CRP levels are independent risk factors for the occurrence of carotid artery calcification, and elevated eGFR levels are independent protective factor. The prediction model based on the above factors has certain predictive value for the occurrence of carotid artery calcification.

Abstract:Vascular calcification refers to the process of calcium salt deposition in the blood vessel wall, leading to vascular stiffening and loss of elasticity. It commonly occurs in middle-aged and elderly individuals, especially those with chronic conditions such as atherosclerosis, hypertension, diabetes, and chronic kidney disease. Vascular calcification is an active process, and one of the key events is the transdifferentiation of smooth muscle cells into osteoblast-like cells. These cells release calcium ions during the calcification process, leading to calcium salt deposition and the formation of calcified plaques. Vascular calcification is regulated by various factors, including high levels of phosphate and calcium, oxidative stress, and mechanical stress. Traditional Chinese medicine research has shown potential in attenuating vascular calcification, with substances such as Ganoderma lucidum spore powder and its derivatives, Panax notoginseng, baicalin, geniposide, and triptolide. These studies provide important evidence for further understanding and intervention in vascular calcification and reveal potential inhibitory factors that could be explored for future treatments.

Abstract:Aim To explore the correlation between coronary artery calcification score (CACS) and retinal arteriosclerosis using artificial intelligence assisted analysis software. Methods 511 examinees who underwent physical examinations in the Department of Health Medicine of General Hospital of Eastern Theater Command in 2022 were selected as the research subjects, they were divided into a coronary artery calcification (CAC) group (＞0,1 cases) and a non CAC group (＝0,0 cases) based on the Agatston score, the clinical data of the two groups of examinees were compared using independent sample t-tests and chi square tests. According to the condition of retinal arteriosclerosis, the examinees were divided into three groups:normal retinal artery group, weakened retinal artery elasticity group and retinal arteriosclerosis group. Kruskal Wallis H test was used to compare the quantitative indicators of CACS and retinal microvasculature among the three groups; Spearman correlation analysis was used to study the correlation between CAC grading and clinical indicators, as well as quantitative indicators of retinal microvasculature; binary Logistic regression was used to analyze the correlation between retinal arteriosclerosis and CAC. Results The age, number of smokers, waist circumference, hip circumference, waist to hip ratio (WHR), body mass index (BMI), systolic blood pressure, serum creatinine (SCr), blood uric acid (BUA), blood urea nitrogen (BUN), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), triglyceride (TG) in the CAC group were higher than those in the non CAC group, and the difference was statistically significant (all P＜0.05). There were statistically significant differences in total CACS and AVR among the three groups of normal retina, weakened retinal artery elasticity and retinal arteriosclerosis (all P＜0.05), while there was no significant difference in CRAE and CRVE (all P＞0.05). The CACS level and total score were positively correlated with age, smoking status, waist circumference, hip circumference, WHR, BMI, systolic blood pressure, BUN, SCr, BUA, homocysteine (Hcy), FBG, 2 hour postprandial blood glucose (2h PBG), HbA1c, TG (all P＜0.05), and negatively correlated with gender, total cholesterol (TC), high density lipoprotein cholesterol (HDLC; all P＜0.05), but not with diastolic blood pressure and low density lipoprotein cholesterol (LDLC; all P＞0.05). The degree of retinal arteriosclerosis was positively correlated with age, waist circumference, hip circumference, WHR, BMI, systolic blood pressure, diastolic blood pressure, calcification scores of left main artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), right coronary artery (RCA), total CACS, BUN, FBG, 2h PBG, HbA1c and TG (all P＜0.05), and negatively correlated with TC, HDLC and LDLC (all P＜0.05), but not with gender, smoking status, pulse, SCr, BUA and Hcy (all P＞0.05). CAC level was negatively correlated with AVR (r＝－0.166, P＜0.05), and positively correlated with retinal arteriosclerosis level (r＝0.199, P＜0.05), but not significantly correlated with CRAE and CRVE (all P＞0.05). There was a correlation between CAC and retinal arteriosclerosis (P＜0.001). After adjusting for age, gender, smoking status, WHR, BMI, systolic blood pressure, FBG, SCr, BUA, BUN, and HDLC factors, the correlation between CAC and retinal arteriosclerosis still exists (P＝0.048). Conclusion AI assisted analysis of retinal vascular diameter and degree of retinal arteriosclerosis is related to CAC, which plays a positive role in risk assessment of atherosclerotic heart disease.

Abstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) comprised of 692 amino acids is the ninth member of protease family. It binds to the low-density lipoprotein receptor(LDLR), leading to elevated levels of circulating low-density lipoprotein cholesterol(LDLC), which can lead to a number of cardiovascular diseases, and among then the relationship with cardiovascular calcification has recently received attention. Cardiovascular calcification is a kind of ectopic mineralisation in the cardiovascular system, which is mainly characterised by the production of mineral deposits in the vascular wall and vascular valves, and its pathogenesis is related to lipoprotein content, platelet activity, matrix vesicle (MV) release and inflammation, through which PCSK9 may be involved in the occurrence of cardiovascular calcification.Therefore, this article reviews the relationship between PCSK9 and cardiovascular calcification, emphasizing the specific role of PCSK9 in affecting cardiovascular calcification through various pathways, assisting in setting up emerging applications of PCSK9 amid vessel biological science and recognize innovative molecular mechanisms for its treatment.

Abstract:Coronary artery calcification is commonly seen in patients with coronary atherosclerotic heart disease, but the mechanism of its happening, development, and formation is less known. Gla-rich protein (GRP) is a newly discovered vitamin K-dependent protein. Studies have shown that GRP inhibits the formation and maturation of calcified crystals by binding to minerals, participates in the inhibition pathway of matrix Gla protein-fetuin-A calcification, blocks the signalling pathway of calcification inducers and has an anti-inflammatory effect, thus playing a role in inhibiting vascular calcification. In this paper, the research progress of GRPs participation in the mechanism of coronary artery calcification will be conducted in the hope of providing a new direction for the prevention and treatment of coronary artery calcification.