Abstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease, which is mainly expressed in hepatocytes. PCSK9 binds to low density lipoprotein receptor (LDLR) forming PCSK9-LDLR complex, and leads to LDLR degradation in lysosomes, which finally results in the reduction of cell membrane LDLR protein level and the elevation of plasma low density lipoprotein cholesterol (LDLC) level. PCSK9 inhibitors have become a hot spot in the research of hypercholesteremia and atherosclerotic cardiovascular disease (ASCVD) drugs discovery. There are three globally marketed PCSK9 inhibitors including evolocumab, alirocumab and PCSK9 siRNA drug inclisirian (Leqvio). This article reviewed the structure, functions and inhibitors of PCSK9.

Abstract:The prevalence of chronic kidney disease (CKD) is increasing year by year, and cardiovascular disease (CVD) is the main cause of death. Patients with CKD are often complicated with abnormal lipid metabolism, which is a significant factor in promoting the occurrence and development of CVD. However, the relationship between dyslipidemia in CKD patients and morbidity and mortality of CVD has its particularity, and it is controversial whether various lipid-lowering treatments can effectively improve CVD in patients with CKD. Therefore, this article reviews the pathophysiological mechanism and correlation between abnormal lipid metabolism and CKD patients with CVD, which is of exceedingly significance to reduce the incidence of CVD and improve the prognosis of CKD.

Abstract:Atherosclerosis is the main cause of most cardiovascular diseases, but its pathogenesis is complicated and has not been fully understood. More and more studies have shown that the disorder of lipid metabolism may play an important role in the initiation and development of atherosclerosis. As a group of bioactive lipids participating in cell structure component and signal transduction, sphingolipids have been proved to be abnormal in blood and vascular lesion in patients with cardiovascular diseases. Some sphingolipids may be potential biomarkers and therapeutic targets in cardiovascular diseases. This review is focused on the influences and regulatory mechanisms of sphingolipids on the initiation and development of atherosclerosis trying to find new ideas and molecular targets for the prevention and treatment of atherosclerosis.

Abstract:Aim To explore the effects of yam polysaccharide (RDPS-Ⅰ) on myocardial injury and tyrosine protein kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in septic rats. Methods Ninety rats were randomly divided into:RDPS-Ⅰ low (1.0 g/kg), medium (2.0 g/kg), and high (3.0 g/kg) dose groups, model group, positive control group and sham operation group. The cecal ligation and perforation method was used to establish a sepsis rat model, after the model was completed, RDPS-Ⅰ low, medium and high dose groups were given corresponding dose yam polysaccharide by gavage respectively; The positive control group was given 200 mg/kg subcutaneous injection of 4 mL/kg ampicillin solution; The other two groups were given normal saline, and intervened once every 12 hours, for 6 consecutive days. After the intervention, the hemodynamic indicators of the rats were measured, including mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and heart rate (HR); Hematoxylin-Eosin (HE) staining was used to observe the pathological changes of septic rat myocardium; TUNEL staining was used to detect cardiomyocyte apoptosis of septic rat; enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory cytokines in septic rat serum; Western blot was used to test the expression level of JAK2/STAT3 signaling pathway proteins in rat myocardial tissue. Results Compared with the sham operation group, the myocardial tissue was disordered and occurred with severe inflammatory cell infiltration in the model group; LVSP, HR, MAP decreased by 56%, 54%, 55% (P＜0.05). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-κB (NF-κB) in serum and p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rates in myocardial tissue were increased by 2.5,1.4,1.9,1.9,2.6,2.26 and 3.67 times (P＜0.05), respectively. Compared with model group, the degree of myocardial tissue disorder and inflammatory cell infiltration were gradually relieved after RDPS-Ⅰ intervention; LVSP, HR and MAP increased by 0.4,0.35 and 0.34 times in low dose RDPS-Ⅰ group, respectively; TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 28%, 19%, 18%, 26%, 27%, 29%, 25%, respectively. LVSP, HR and MAP increased by 0.2,0.67 and 0.83 times in medium dose RDPS-Ⅰ group, respectively. TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 45%, 41%, 40%, 50%, 49%, 50%, 50%, respectively. LVSP, HR and MAP increased by 1.1,1.10 and 1.15 times in high dose RDPS-Ⅰ group (P＜0.05), respectively. TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 64%, 63%, 63%, 66%, 70%, 66%, 70% (P＜0.05), respectively. Conclusion Yam polysaccharide can reduce inflammation, and improve myocardial injury and dysfunction in septic rats, which may be related to the inhibition of JAK2/STAT3 signaling pathway.

Abstract:Aim To investigate whether body mass index (BMI) or obesity is associated with the prevalence of abdominal aortic calcification (AAC). Methods 3 116 participants older than 18 were extracted from the data of the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014. AAC was defined based on dual-energy X-ray absorptiometry (DXA). Logistic regression was performed to analyze the association between BMI or obesity and AAC. The adjusted odds ratio (OR) among subgroups was illustrated in the forest map. Restricted cubic spline regression was fitted to explore the potential nonlinear relationship. Results BMI was inversely associated with AAC even after adjusted for confounders (OR＝0.9,5%CI was 0.81～0.98, P＝0.013), and the obesity was more likely to prevent AAC than normal BMI (OR＝0.8,5%CI was 0.16～0.94, P＝0.037). The association was still significant in the subgroups of male (OR＝0.2,5%CI was 0.69～0.96), age＞60 (OR＝0.9,5%CI was 0.80～0.99), without hypertension (OR＝0.6,5%CI was 0.62～0.93) and without diabetes (OR＝0.7,5%CI was 0.78～0.97). Restricted cubic spline regression revealed a non-linear relationship between BMI and AAC (P＝0.0023). ConclusionBMI was inversely associated with the prevalence of AAC, which could be a new predictor of AAC in the clinical practice.

Abstract:Aim To investigate the correlation between plasma miR-1228-5p, miR-34a-5p, miR-192-5p and miR-30a-3p levels and premature coronary artery disease (PCAD) and their early screening value as biomarkers. Methods According to inclusion criteria and exclusion criteria, 6 patients with clearly diagnosed PCAD were included as PCAD group and 6 heathy subjects as control group. Blood was collected from the PCAD group and the control group, and serum samples were extracted and stored. The miRNA levels in the serum of the two groups were detected using DNBseq platform, and the miRNA with significant differences were screened. According to inclusion and exclusion criteria, blood from 78 patients with PCAD, 75 patients with late-onset coronary artery disease and 69 healthy subjects were collected and the selected miRNAs were verified by qPCR. Coronary angiography reports of patients with PCAD were analyzed, and the severity of coronary artery disease was evaluated by Gensini score. Spearman correlation test was used to analyze the correlation between the degree of coronary stenosis and the miRNA. ROC curve was used to analyze the diagnostic value of plasma levels of miR-1228-5p, miR-34a-5p, miR-192-5p and miR-30a-3p for PCAD, and multivariate Logistic regression was used to analyze the influencing factors of PCAD. Results DNBseq platform analysis showed 33 differentially expressed miRNAs, including 17 up-regulated miRNAs and 16 down-regulated miRNAs. The 5 miRNAs with the most significant difference levels were miR-1228-5p, miR-34a-5p, miR-192-5p, miR-424-3p and miR-30a-3p. qPCR results showed that compared with the control group, plasma miR-1228-5p, miR-34a-5p, miR-192-5p and miR-30a-3p levels were increased by 1.7 times, 1.4 times, 0.7 times and 2.5 times in patients with PCAD (P＜0.05). There was no significant difference in miR-424-3p level between the two groups (P＞0.05). Spearman correlation analysis showed that plasma levels of miR-1228-5p and miR-34a-5p were positively correlated with the degree of coronary stenosis in patients with PCAD (r＝0.307, P＝0.004; r＝0.238, P＝0.036). ROC curve analysis showed that the areas under ROC curve for the diagnosis of PCAD by miR-1228-5p, miR-34a-5p, miR-192-5p and miR-30a-3p were 0.3,0.2,0.731 and 0.798, respectively. The area under ROC curve of the combined diagnosis was 0.990, and 95%CI was 0.970～1.000. Conclusions The plasma levels of miR-1228-5p, miR-34a-5p, miR-192-5p and miR-30a-3p in patients with PCAD were significantly increased. The combined detection showed high accuracy in the diagnosis of PCAD, which is expected to be new biomarkers for preliminary screening of PCAD.

Abstract:Aim To observe whether the new electrocardiogram (ECG) diagnostic criteria RLⅠ+SV4 and SD+SV4 are suitable for the diagnosis of hypertension complicated with left ventricular hypertrophy (LVH), and to study the clinical value of 13 ECG diagnostic criteria and the combined application of new and commonly used criteria for hypertension complicated with LVH. Methods Using the left ventricular mass index (LVMI) measured by echocardiography as the standard, 280 inpatients with essential hypertension or a history of hypertension treatment were selected, including 94 patients with hypertension complicated with LVH (LVH group), 186 patients with normal ventricle (normal left ventricle group). 12-lead ECG is recorded simultaneously. Receiver operating characteristic curve (ROC) for various ECG diagnostic criteria was plotted and the area under curve (AUC) of the ROC was compared. The sensitivity and specificity of various diagnostic criteria were calculated. The diagnostic value of RLⅠ+SV4, SD+SV4 and RLⅠ+SV4, SD+SV4 combined with the currently recognized ECG diagnostic criteria for hypertensive patients with LVH was analyzed. Results In a single ECG lead, RLⅠ, the R wave in lead Ⅰ, was one of the better predictors of LVH (AUC＝0.63, P＜0.01). In the study of the sum of the amplitudes of the two leads for the diagnosis of LVH, the sensitivity of the RLⅠ+SV4 standard (AUC＝0.64, P＜0.01) was 50%, and the specificity was 71%; Paired chi-square test showed no significant difference between RLⅠ+SV4 diagnosis of LVH and the gold standard (LVMI to determine LVH). The SD+SV4 standard (AUC＝0.59, P＜0.05) had a sensitivity of 31% and a specificity of 87%, in which the SD wave was the S wave with the largest amplitude in the 12 leads. RLⅠ+SV4 combined with Sokolow-Lyon voltage standard could improve the sensitivity of diagnosing hypertension complicated with LVH, the sensitivity was 59%, and the specificity was 60%. Conclusions RLⅠ+SV4 standard has higher AUC, which is suitable for the initial screening of hypertensive patients with LVH; RLⅠ+SV4 combined with Sokolow-Lyon voltage standard can improve the sensitivity of diagnosis. The clinical applicability of SD+SV4 standard is not as high as that of RLⅠ+SV4 standard.

Abstract:Aim To analyze the longitudinal peak strain (LPS) of left ventricular subendocardial myocardium, middle myocardium and subepicardial myocardium in patients with diabetes mellitus complicated with microangiopathy by speckle tracking stratified strain technique, so as to evaluate the myocardial function in patients with diabetes mellitus complicated with microangiopathy. Methods 40 patients with type 2 diabetes mellitus (T2DM) were collected and classified according to whether they had microvascular disease:20 cases of T2DM group, 20 cases of T2DM microangiopathy group. 20 cases of healthy volunteers were collected as control group. All subjects underwent conventional echocardiographic examination, and the two-dimensional echocardiographic images of at least three cardiac cycles were collected and stored. The collected two-dimensional dynamic images were imported into the offline analysis software QLab13.0. The global longitudinal strain (GLS) of the left ventricle during systole was obtained by recording the endocardium and epicardium. After that, the left ventricular three-layer myocardium was recorded by stratified strain mapping, and the endocardial longitudinal peak strain (LPSendo), middle myocardial longitudinal peak strain (LPSmid) and epicardial longitudinal peak strain (LPSepi) were obtained. Then the transmural strain pressure difference of left ventricle was obtained from the LPS difference between subendocardial and subepicardial myocardium. Results Compared with control group, GLS in T2DM microangiopathy group significantly decreased by 2.15% (P＜0.05), but there was no significant difference in GLS in T2DM group. Compared with T2DM group, GLS in T2DM microangiopathy group significantly decreased by 1.79% (P＜0.05). Compared with control group, the LPSendo in T2DM group significantly decreased by 3.09% (P＜0.05), but there was no significant difference in the LPSmid and LPSepi in T2DM group (P＞0.05), and LPSendo, LPSmid and LPSepi in T2DM microangiopathy group significantly decreased by 4.20%, 3.38% and 3.16%. Compared with T2DM group, LPSendo, LPSmid and LPSepi in T2DM microangiopathy group respectively decreased by 1.11%, 2.68% and 3.19% (P＜0.05). Compared with control group, ΔLS in T2DM group decreased by 2.59% (P＜0.05), but there was no significant difference in ΔLS in T2DM microangiopathy group, and compared with T2DM microangiopathy group, ΔLS in T2DM group was significantly decreased by 1.89% (P＜0.05). Correlation analysis showed that GLS, LPSendo, LPSmid and LPSepi were negatively correlated with diabetic course (r＝－0.491, －0.546, －0.578 and －0.592, all P＜0.001), there was no linear correlation between ΔLS and diabetic course (r＝0.305, P＞0.05). Conclusion The application of stratified strain technique can sensitively detect the damage of endocardium in diabetic patients and different levels of myocardium in diabetic patients with microangiopathy, which can provide clinical diagnostic basis.

Abstract:Aim To explore the predictive value of peripheral blood angiotensinⅡ (AngⅡ), ischemia-modified albumin (IMA) and C-reactive protein (CRP) for venous thromboembolism (VTE). Methods 170 patients with VTE who were treated in Shijiazhuang People's Hospital from June 2018 to January 2021 were selected as the study group, and 101 healthy subjects in the same period were selected as the control group. The levels of AngⅡ, IMA and CRP in the two groups were detected in strict accordance with the instructions of ELISA kit. Logistic regression analysis was used to analyze the correlation between AngⅡ, IMA and CRP and VTE. Results The levels of AngⅡ, IMA and CRP in the study group were significantly higher than those in the control group, and the level of D-dimer in the study group was significantly lower than that in the control group (P＜0.05). There was no significant difference in HDL, LDL and platelet count between the two groups (P＞0.05). The levels of triglyceride and fibrinogen in the study group were significantly higher than those in the control group (P＜0.05). Logistic regression analysis showed that AngⅡ, IMA and CRP were independent risk factors for VTE. In the ROC curve, the sensitivity and specificity of AngⅡ, IMA and CRP were 97.6% and 88.9% respectively. Conclusion The three indexes of AngⅡ, IMA and CRP in peripheral blood have good value in the prediction of VTE and are worthy of further promotion in clinic.

Abstract:Aim To evaluate the safety and clinical efficacy of high atrial septal pacing (HASP) and compare the difference between HASP and right atrial appendage pacing (RAAP) in atrial electrical activity and atrial structure.Methods A retrospective analysis of 142 patients with sick sinus syndrome(SSS)who underwent dual-chamber pacemaker implantation in the Department of Cardiology of the Second Affiliated Hospital of Harbin Medical University from January 2013 to January 2017 was performed. According to the implantation site of atrial pacing lead, the patients were divided into two groups:HASP group (n＝100) and RAAP group (n＝42). Preoperative and postoperative P-wave duration, P-wave dispersion, left atrial diameter, and atrial lead pacing parameters (pacing threshold, perception, impedance) were recorded, and retrospective analysis and comparative study were conducted. Results There were no significant differences in gender, age, previous disease, history of smoking and drinking among the 142 patients enrolled. The duration of P-wave in RAAP group was (128.03±17.11) ms before operation and (144.82±21.37) ms after operation, the duration of P-wave in HASP group was (125.48±13.20) ms before operation and (102.08±15.23) ms after operation, there was a statistically significant difference in the postoperative P-wave duration between the two groups (P＜0.001). The dispersion of P-wave in RAAP group was (27.33±10.12) ms before operation and (18.64±6.59) ms after operation, the dispersion of P-wave in HASP group was (27.12±8.58) ms before operation and (18.89±4.85) ms after operation. The dispersion of P-wave after operation in both groups was reduced compared with that before operation, but there was no significant difference between the two groups (P＝0.47). It seemed that there were no difference between RAAP and HASP in left atrial diameter (34.07±5.71) mm vs. (32.48±4.19) mm (P＝0.10). The pacing parameters in the HASP group were stable, and no additional complications were observed in this group. During the program-controlled follow-up 1 year after the pacemaker implantation, 16.7% of the patients in the RAAP group had atrial fibrillation (AF), while the percentage was only 4.0% in the HASP group, the difference between the two groups was statistically significant (P＝0.015). After 2 years following, there was 28.6% patients in RAAP group having AF, only 17.0% in HASP group, the two groups had no statistical significance. Conclusion HASP is a safe and feasible pacing method that can significantly shorten the P-wave duration and is expected to reduce the risk of atrial fibrillation in patients.

Abstract:Vulnerable plaque refers to the plaque with poor stability in the arterial wall, which is easy to rupture and fall off, leading to the formation of in situ thrombus or multiple microemboli. Carotid atherosclerotic vulnerable plaque is the main pathogenic mechanism of ischemic stroke, and carotid plaque vulnerability increases the occurrence of cerebral ischemic events. Therefore, early identification of vulnerable plaques is of great significance for intervening high-risk factors for stroke and improving stroke prognosis. In addition to various imaging techniques, circulating biomarkers provide an adjunct to the identification of vulnerable carotid plaques. This article reviews previous studies, discussing novel biomarkers capable of identifying carotid vulnerable plaques.

Abstract:Atherosclerosis is considered as a chronic inflammatory disease that involves multiple cell types and factors. The outside layer of the vessels plays a vital role during pathological development. Under pathological conditions such as obesity and inflammation, perivascular adipose tissue (PVAT) will release adipokines and inflammatory factors through adipocyte phenotype transformation and regulate various inflammatory cells. PVAT regulates the immune response of blood vessels in an “outside-inside” manner and further regulates atherosclerosis. Intervention of PVAT may be a new strategy for prevention and treatment of atherosclerosis.

Abstract:Restenosis is the main problem after interventional therapy in lower extremity arteriosclerosis obliterans.Fatty acid-binding protein 4 (FABP4) is mainly secreted by macrophages and promotes lipid accumulation in macrophages, thereby converting macrophages into foam cells and causing atherosclerosis. After atherosclerotic occlusion interventional therapy, vascular endothelial cells can also specifically secrete FABP4; FABP4 acts on vascular smooth muscle cells, causing them to proliferate and migrate to form proliferative intima, and promote inflammatory response, resulting in restenosis after interventional therapy. It is suggested that FABP4 may be an important target for the treatment of atherosclerosis and restenosis after interventional therapy. This article briefly describes the biological characteristics and functions of FABP4, and reviews its role and mechanism in atherosclerosis and restenosis after interventional therapy.

Abstract:Cardiovascular system development and cardiovascular disease are extremely complex process. Furin is an endonuclease and plays an important role in the development of cardiovascular system and the occurrence and progression of cardiovascular diseases. In this paper, the role of Furin in cardiovascular system development and cardiovascular diseases was reviewed, and the relationship between Furin and cardiovascular diseases was explored, which provides a new target for the prevention and treatment of various cardiovascular diseases.