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:In recent years, more and more studies have found that phase separation plays an important role in the onset and progression of cardiovascular diseases. Phase separation refers to the process in which biological macromolecules, such as proteins and nucleic acids, spontaneously segregate into concentrated and diluted phases under certain conditions. This process creates distinct functional compartments within cells and is involved in various cellular biological functions. The driving forces of phase separation include multivalent interactions such as electrostatic interactions, hydrophobic interactions, and π-π stacking. Key protein regions that promote phase separation include intrinsically disordered regions, low complexity domains, folded domains, and nucleic acid binding domains. This article reviews recent progress in understanding the role of phase separation in cardiovascular diseases, including heart failure, myocardial fibrosis, and atherosclerosis, with a particular focus on the last five years of research. Future studies should aim to elucidate the specific mechanisms of phase separation in cardiovascular diseases and explore its potential as a therapeutic target.

Abstract:Aim To explore the effects of exercise during pregnancy on renal structure, function and angiotensin Ⅱ (Ang Ⅱ)/transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) signaling pathway in 3-month-old offspring of spontaneously hypertensive rats (SHR), the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs. Methods After mating SHR and WKY rats, pregnant rats were randomly divided into sedentary group (p-WKY-SED, p-SHR-SED) and exercise group (p-WKY-EX, p-SHR-EX). Blood pressure, serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats. HE staining, Masson staining, ELISA and Western blot were used to detect the renal structure, collagen volume fraction, AngⅡ concentration, renin-angiotension-aldosterone system (RAAS) and protein expression related to fibrogenic signal pathway in 3-month-old rats. Results (1) The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group. The SBP, DBP and MAP of SHR male offspring rats were significantly decreased by exercise during pregnancy (P＜0.05), but had no effect on the female offspring rats (P＞0.05). (2) There was no significant difference in serum urea nitrogen and creatinine among the groups (P＞0.05). (3) The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P＜0.05), and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group (P＜0.05). (4) Renal AngⅡ level of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group, and renal AngⅡ level of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group (P＜0.05). (5) The expression levels of angiotensinⅡ type 1 receptor (AT1R), TGF-β1 and CTGF protein in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P＜0.05), while the expression levels of angiotensin converting enzyme 2 (ACE2), angiotensinⅡ type 2 receptor (AT2R) and MasR protein in p-SHR-SED group were significantly lower than those in p-WKY-SED group (P＜0.05). Conclusion (1) Exercise during pregnancy can significantly decrease the blood pressure of 3-month-old male offspring rats of hypertensive rats, but has no significant effect on that of 3-month-old female offspring. (2) Exercise during pregnancy may reduce renal fibrosis in 3-month-old female/male offspring of hypertensive rats by regulating RAAS balance and inhibiting AngⅡ /TGF-β1/CTGF signaling pathway.

Abstract:Aim To study the regulatory effect of acupuncture pretreatment on ferroptosis of nerve cells in rats with ischemic stroke. Methods Sixty SD rats were randomly divided into sham middle cerebral artery occlusion (MCAO) group, MCAO group, and acupuncture+MCAO group. In the acupuncture+MCAO group, the acupuncture points of DU26, PC6, and SP6, were selected for acupuncture pretreatment, once a day for a total of 5 days. After pretreatment, MCAO or sham MCAO models were prepared. The Zausinger sextintegral method was used to score the neurological function of rats, and the infarct volume of brain tissue was calculated by TTC staining. Electron microscopy was used to observe the pathomorphological changes of brain tissue. The iron content was detected by colorimetric method, the content of malondialdehyde (MDA) and glutathione (GSH) was determined by ELISA, and the expression of glutathione peroxidase 4 (GPX4) was detected by immunofluorescence. Results Compared with the sham MCAO group, the MCAO group had a decrease in neurological function scores, a significant increase in infarct volume, a decrease in the number of mitochondria under electron microscopy, a rupture and vacuolization of the inner mitochondrial cristae, an increase in the contents of iron and MDA in brain tissue, and a decrease in GSH content and GPX4 expression. Compared with the MCAO group, the acupuncture+MCAO group had an increase in neurological function scores, a decrease in infarct volume, a large number of mitochondria under electron microscopy, a clear structure, a decrease or disordered arrangement of some mitochondrial crest structures, a decrease in the contents of iron and MDA in brain tissue, and an increase in GSH content and GPX4 expression. Conclusion Acupuncture pretreatment can alleviate neurological damage in rats, and its mechanism may be related to regulating iron, GSH and MDA contents in brain tissue, and GPX4 expression, improving cell antioxidant capacity and inhibiting nerve cell ferroptosis.

Abstract:Aim To observe the effects of receptor interacting protein 2 (RIP2) on macrophage inflammatory activation and polarity transformation, and to explore the mechanism of RIP2 in macrophage phagocytosis of oxidized low density lipoprotein (ox-LDL). Methods THP-1 derived macrophages were treated with different doses (0,5 and 50 mg/L) of ox-LDL for 24 hours, and treated with 50 mg/L ox-LDL for 8,6 and 24 hours. Real-time quantitative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages, and ELISA was used to detect the secretion of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). Three pairs of RIP2 siRNA were designed, transfecting them into cells using hiperfict transfection reagent, real-time quantitative PCR and Western blot were used to detect the expression of RIP2 mRNA and protein in THP-1 derived macrophages after transfection, in order to screen for the optimal siRNA transfection concentration and the most effective pair of siRNA.After transfection with the most effective RIP2 siRNA, cells were treated with 50 mg/L ox-LDL for 24 hours, ELISA was used to detect the secretion of TNF-α, MCP-1, interleukin-10 (IL-10) and interleukin-12 (IL-12), real-time quantitative PCR was used to detect the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1), flow cytometry was used to detect the expression of cell surface antigens CD86, CD80 and CD163. Results Ox-LDL induced the expression of RIP2 in macrophages in a dose-dependent and time-dependent manner. With the increase of ox-LDL treatment dose and time, the expression of RIP2 mRNA and protein increased. Among them, the expression of RIP2 protein in the 50 mg/L group was 7.6 times of the control group, and the expression of RIP2 protein in the 24 h group was 17.9 times of the control group (P＜0.001). The ELISA results showed that with the increase of ox-LDL treatment dose and time, the secretion of TNF-α and MCP-1 increased (P＜0.05). After transfection of RIP2 siRNA into cells, ELISA results showed that the secretion of TNF-α, MCP-1 and IL-10 in the ox-LDL group was 2.4 times, 2.9 times and 1.8 times of the control group (P＜0.01), and the secretion of IL-12 decreased by 34.2% compared to the control group (P＜0.01); the secretion of TNF-α, MCP-1 and IL-10 in the siRNA+ox-LDL group decreased by 37.4%, 45.3% and 27.4%, respectively, compared to the ox-LDL group (P＜0.01), while the secretion of IL-12 increased by 31.4% (P＜0.05). The results of flow cytometry and real-time quantitative PCR showed that the expression of CD86, CD80 and iNOS mRNA in the ox-LDL group was 14.2 times, 33.8 times and 4.5 times of those of the control group, respectively, while the expression of CD163 and Arg-1 mRNA decreased by 33.4% and 43.0%, respectively, compared with the control group (P＜0.05); the expression of CD86, CD80 and iNOS mRNA in the siRNA+ox-LDL group decreased by 27.6%, 29.3% and 34.3%, respectively, compared to the ox-LDL group, while the expression of CD163 and Arg-1 mRNA increased by 30.3% and 38.6%, respectively (P＜0.05). Conclusion RIP2 expression in macrophages can be induced by ox-LDL in a dose-dependent and time-dependent manner. RIP2 gene silencing can inhibit ox-LDL induced M1 macrophage transformation.

Abstract:Aim To explore the effect of age on myocardial remodeling after percutaneous coronary intervention (PCI) in patients with acute anterior myocardial infarction. Methods This study was a cross-sectional study analyzing clinical data of regular follow-up at 1,3, 6 and 12 months after PCI for acute anterior myocardial infarction. According to the age of the patients, they were divided into a low age group (＜65 years old) and a high age group (≥65 years old). The differences in baseline data, biochemical indexes, coronary angiography, inflammatory factor levels, and cardiac ultrasound indexes between the two groups were analyzed, and the correlation analysis between age and inflammatory factors and the multivariate linear regression analysis of diastolic function were performed. Results A total of 87 patients with acute anterior myocardial infarction were selected, aged (62±13) years, including 67 males (77.0%), 43 in the low age group and 44 in the high age group. Compared with the low age group, the levels of inflammatory factors such as C-reactive protein, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in the high age group, while ultrasound indicators such as mitral valve annulus septal e′, mitral valve flow velocity E/A, and mitral valve annulus sidewall e′ decreased (P＜0.05). Older age was an independent risk factor for a decrease in mitral valve flow velocity E/A, mitral valve annulus sidewall e′ and mitral valve annulus septal e′ in patients with acute anterior myocardial infarction 6 months after PCI (P＜0.05). Conclusion Age is an independent risk factor for reduced diastolic function after PCI in acute anterior myocardial infarction, inflammatory factor such as IL-1β, IL-6 and TNF-α may play a role in the impaired diastolic function after PCI in age-related acute anterior myocardial infarction.

Abstract:Aim To explore the predictive value of serum free triiodothyronine (FT3) on the long-term prognosis of patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods All the subjects were from a prospective cohort study (PRACTICE study). In this study, 15 250 patients with coronary heart disease after PCI in the First Affiliated Hospital of Xinjiang Medical University were selected, and the clinical data, FT3 and creatinine were collected. All the subjects were followed up regularly, and the primary follow-up endpoints were all-cause mortality and cardiogenic mortality, the secondary endpoints were major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE). According to the admission criteria, 3 109 patients were finally included in this study. According to the baseline value of FT3, patients were divided into normal FT3 group (FT3:3.65～6.8 pmol/L, 1 446 cases) and low FT3 group (FT3＜3.65 pmol/L, 1 663 cases). Kaplan-Meier analysis was used for survival analysis, and Log-rank test was used for survival comparison. Multivariate Cox regression analysis was used to evaluate the risk factors of the follow-up results of the two groups. Results Compared with the normal FT3 group, all-cause mortality and cardiogenic mortality in the low FT3 group increased significantly (P＜0.05). Kaplan-Meier analysis showed that the cumulative risk of all-cause mortality and cardiogenic mortality increased in the low FT3 group (P＜0.05).Multivariate Cox regression analysis indicated that the risk of all-cause mortality increased by 1.639 folds in the low FT3 group (HR＝2.9,5%CI:1.385～5.348, P＝0.007), while no statistical difference was found in cardiogenic mortality after adjusting for multiple factors (P＝0.125). Conclusion The decrease in serum FT3 levels has important predictive value for all-cause mortality after PCI in patients with coronary heart disease.

Abstract:Aim To investigate the association between cardiovascular health (CVH) score based on life's essential 8 (LE8) on cognitive function and the mediation role of neutrophil-to-lymphocyte ratio (NLR) between them in older adults, providing basis for the prevention and control of cognitive impairment. Methods The study population was selected from the National Health and Nutrition Examination Survey (NHANES) 2011—2014 two cycles of 60 years and above, demographic characteristics, medical history and other variables were collected, the participants' CVH scores were calculated according to LE8 defined by American Heart Association, and cognitive function was assessed using the digit symbol substitution test. The relationship between CVH and cognitive function was explored using a weighted linear regression analysis, and the dose-response relationship was analyzed using a restricted cubic spline. Moreover, mediation analysis was used to explore the role of NLR in mediating the relationship between CVH score and cognitive function. Results A total of 2 510 participants were included in this study. After adjusting for relevant factors, cognitive function was positively associated with moderate CVH group score (β=3.6,5%CI:1.43~ 5.30) and high CVH group score (β=6.1,5%CI:2.89~ 9.13) compared with the low CVH group score. The LE8 single factor of diet score (β=0.4,5%CI:0.01~0.06), physical activity score (β=0.4,5%CI:0.02~0.05), tobacco exposure score (β=0.5,5%CI:0.02~0.08), blood pressure score (β=0.3,5%CI:0.01~0.05) and blood glucose score (β=0.6,5%CI:0.03~0.09) were positively correlated with cognitive function score. The results of restricted cubic splines showed that the score of CVH was linear positively correlated with the score of cognitive function. The indirect effect of CVH on cognitive function via NLR was 0.002 (P＞0.05), and the proportion of mediating effect was 1.29% (P＞0.05), indicating the mediating effect of NLR on the relationship between CVH score and cognitive function was not significant. Conclusions The CVH score based on the LE8 was positively correlated with cognitive function in older adults, underscoring the crucial role of maintaining optimal CVH levels in supporting cognitive health. However, the NLR, as an indicator of inflammation, did not exhibit a significant mediating effect between the CVH score and cognitive function. The relationship between these variables might be influenced by other mechanisms.

Abstract:Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lipoprotein cholesterol (non-HDLC/HDLC) exposure on atherosclerotic cardiovascular disease(ASCVD). Methods A prospective cohort study was conducted. A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006—7,8—2009 and 2010—2011 were selected as the study subjects. Groups were divided into Q1, Q2, Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles. Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups, and Log-rank test was used to compare the differences among groups. Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD. Results The average follow-up was (10.19±2.21) years, and 5 003 new cases of ASCVD occurred. The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49%, 8.71%, 10.86% and 14.85%, respectively(Log-rank P＜0.01). Multivariate Cox regression analysis showed that compared with group Q1, the HR(95%CI) of ASCVD in groups Q2, Q3 and Q4 were 1.13(1.03～1.24), 1.18(1.07～1.29), 1.22(1.12～1.34), respectively; the HR(95%CI) of myocardial infarction were 1.15(0.87～1.53), 1.44(1.10～1.88), 1.67 (1.29～2.17), respectively; the HR(95%CI) of revascularization were 1.21 (0.99～1.49), 1.31 (1.07～1.60) and 1.49(1.22～1.81), respectively; the HR(95%CI) of ischemic stroke were 1.17 (1.03～1.32), 1.17 (1.04～1.33) and 1.21 (1.06～1.37), respectively; but the above association was not found when heart failure and atrial fibrillation were used as the outcome events. The restricted cubic spline showed that cumulative non-HDLC/HDLC values were linearly associated with the risk of ASCVD. Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Abstract:Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a complex and diverse disease with great heterogeneity in pathophysiologic mechanisms and treatment prognosis. It is difficult to fully clarify the mechanism by conventional examination. Optical coherence tomography (OCT) visualizes the microstructure of vascular plaques with high resolution and identifies vulnerable plaques more accurately. The aim of this review is to use this technique to delve into the morphological features of MINOCA for a more comprehensive understanding of disease progression. Accurate characterization of plaques and identification of vulnerable plaques can help develop individualized treatment plans, improve prognosis, and reduce mortality.

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 host's 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:Atherosclerosis (As) is a chronic inflammatory arterial wall injury process, and vessel wall cells play an important role in the occurrence and development of As. Vascular endothelial cell (VEC) act as a semi-permeable barrier between vascular smooth muscle cell (VSMC) and vascular lumen, and its injury is the initial stage of As. In addition, Through phenotypic transformation, VSMC could transform into many cell phenotype of the plaques, including macrophage, foam cell, mesenchymal stem cell and so on, and these cells further involved in the occurrence of As. Fibroblast is the main component of vascular adventitia,in pathological conditions, fibroblast differentiate into myofibroblast and participate in the occurrence of As. In this article, we will review the involvement of vascular wall cells in the mechanism of As and its potential therapeutic targets for the treatment of As, which provide new therapeutic ideas for As.