Abstract:Cardiovascular disease remains the major cause of death in China. Atherosclerosis (As) has been a crucial pathological foundation of cardiovascular diseases. It is known that the vulnerable plaques in coronary artery are instability high-risk plaques with a tendency to thrombosis who develop rapidly, which act as the pathologic mechanism of acute coronary syndrome (ACS) and ischemic stroke. Although the current anti-atherosclerosis therapy could reduce 30%～45% of acute myocardial infarction and stroke, residual risk of vulnerable plaques remains high. Therefore, it is critical to reach a better understanding of the pathogenesis for plaque vulnerability to identify and treat adverse cardiovascular events.

Abstract:Aim To investigate the effect of aminolaevulinic acid (ALA)-mediated sonodynamic therapy (SDT) on atherosclerosis plaque. Methods The rabbit atherosclerotic model was established by balloon denudation and an atherogenic diet. The metabolism and distribution of protoporphyrin Ⅸ (PpⅨ) in the plaque were detected by fluorescence microscopy and fluorescence spectrometry at 0,1, 2,3, 4,5 and 6 hours after intravenous injection of ALA (n=3). Animals were randomly divided into control group and SDT group. Apoptosis and macrophage content were detected by TUNEL and immunohistochemistry at 6,2, 24 and 72 hours (n=7) after SDT treatment, and high-frequency ultrasound, pathology and immunohistochemistry were performed at 1 week after SDT treatment. Results Two hours after ALA injection, the content of PpⅨ in plaques reached a peak and mainly distributed in the areas of macrophages. Compared with the control group, the apoptosis of plaque cells increased by 3.1,3.8,7.5 and 4.0 folds at 6,2, 24 and 72 hours after SDT treatment, and the content of macrophages decreased by 45% and 67% at 24 and 72 hours after SDT treatment, and the stenosis rate of femoral artery diameter decreased by 14% at 1 week after SDT treatment. Compared with the control group, the plaque area of SDT group decreased by 38%; the lumen area increased by 86%; the content of lipid, macrophage, proliferative cells, IL-1 beta and TNF-alpha decreased by 64%, 71%, 76%, 62% and 60% respectively; and the content of collagen increased by 117%. Conclusions ALA-PpⅨ is mainly distributed in intraplaque macrophages, SDT induces macrophages apoptosis, and changes the components of plaque to promote plaque stability and reduce the size of plaque. SDT is a potential noninvasive method for the treatment of atherosclerotic plaques.

Abstract:Aim To identify the correlation between chitinase protein 40 (YKL-40) levels including high sensitive C reactive protein (hs-CRP) and the fibrous cap thickness of fibrofatty plaque in coronary culprit 1esions. Methods Clinical data of 60 patients with selective coronary artery angiography diagnosed coronary artery disease were retrospectively analyzed. According to type of coronary disease, patients were divided into 3 subgroups:SAP group (containing 22 stable angina patients), UAP group (containing 28 unstable angina patients), and AMI group (containing 10 acute myocardial infarction patients). Serum hs-CRP and YKL-40 levels were measured before subsequent procedures. The characteristics of the culprit lesions were detected by optical coherence tomography (OCT) before interventional treatment, and the correlation between hs-CRP, YKL-40 and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were analyzed. Results (1)The serum levels of hs-CRP and YKL-40 were significantly higher in AMI group than in SAP and UAP group (all P<0.05), and higher in UAP group than in SAP group (all P<0.05). (2)The fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were smaller in AMI and UAP group than in SAP group (all P<0.05), and there was no significant difference between AMI group and UAP group (P>0.05). Proportion of thin-cap fibroatheroma plaque (all P<0.05), plaque rupture and thrombosis were significantly higher in AMI group than in SAP and UAP group (all P<0.05). Proportion of calcification in plaque was lower in AMI group than in SAP group (P<0.05), and there was no significant difference between AMI group and UAP group (P>0.05). (3)Pearson correlation analysis showed that serum levels of hs-CRP (r=－0.265, P<0.05) and YKL-40 (r=－0.524, P<0.01) were negatively correlated with fibrous cap thickness of fibrofatty plaques. Spearman correlation analysis showed that serum levels of hs-CRP and YKL-40 were positively correlated with plaque rupture (r=0.462 and r=0.499, P<0.01) and thrombosis (r=0.218 and r=0.263, P<0.05). (4)Multiple Logistic regression analysis showed that serum levels of YKL-40 at baseline was independently related to thin-cap fibroatheroma plaque (OR=6.341, P<0.01). Conclusions The serum levels of hs-CRP and YKL-40 in AMI patients were much higher than that in SAP and UAP patients, higher in UAP patients than in SAP patients. Prevalence of thin-cap fibroatheroma plaque, plaque rupture and thrombosis was significantly higher in the AMI patients, while the prevalence of calcification in plaque was more often in SAP patients. Increased serum levels of YKL-40 were independent risk factor of thin-cap fibroatheroma plaque formation.

Abstract:Aim To study the correlation between lipoprotein(a) [Lp(a)] level and coronary vulnerable plaque based on optical coherence tomography (OCT). Methods From January 2015 to August 2018, patients admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University who were diagnosed as coronary heart disease by coronary angiography were examined by OCT. The analysis of the relationship between lipoprotein (a) level and coronary vulnerable plaque were completed by multiple linear regression and other statistical methods. Results A total of 144 patients were enrolled. (1)According to the Lp(a) level, the patients were divided into two groups:Lp(a) ≤300 mg/L group (n＝99) and Lp(a) ＞300 mg/L group (n＝45). The lipid arc of plaque in Lp(a) ＞300 mg/L group was larger than that in Lp(a) ≤300 mg/L group (P＝0.021), and the incidence of vulnerable plaque was higher than that in Lp(a) ≤300 mg/L group (P＝0.001). (2)The patients were divided into vulnerable plaque group (n＝36) and non-vulnerable plaque group (n＝108) by OCT. There were significant differences in sex, smoking history, type 2 diabetes mellitus, body mass index, low density lipoprotein and Lp(a) between the two groups (all P＜0.05). Multivariate Logistic regression analysis showed that Lp(a), type 2 diabetes mellitus and low density lipoprotein were independent influencing factors of vulnerable plaque, and were predictors of vulnerable plaque occurrence. Conclusion The high level of lipoprotein (a) is independently correlated with coronary vulnerable plaques.

Abstract:Inflammatory response plays an important part in the formation and progression of vulnerable plaque. It regulates the lesions locally in the artery as well as the global inflammatory status. Some pro-inflammatory cells and cytokines can reduce the tensile strength of the collagen cap surrounding the plaque and enlarge the necrotic lipid core, thus causing the loss of mechanical stability and plaque rupture. On the other hand, activation of inflammatory response and metabolic disturbance can also instigate endothelial dysfunction, plaque erosion, and further thrombosis. Such process is mediated by several immune cells such as macrophages and lymphocytes, along with other regulatory factors consisting of cholesterol crystals and lipid mediators, shear stress as well as angiogenesis and intraplaque haemorrhage. Moreover, several anti-inflammatory factors are found able to protect the vulnerable plaque from rupture or erosion, highlighting the balance of inflammatory response is essential for the occurrence of acute coronary syndrome (ACS). Thus, targeting specific factors in the inflammatory response may be valuable in screening and treating patients with vulnerable plaque, preventing ACS and improving the prognosis.

Abstract:Acute coronary syndrome often leads to severe cardiovascular events, and the cause of most acute coronary syndromes is coronary atherosclerotic plaque rupture. Therefore, the detection of vulnerable plaque with high risk of rupture is of great significance for the screening and intervention of acute coronary syndrome. Vulnerable plaques have some microstructures such as neovascularization, spotty calcification and cholesterol crystal, which play important roles in the progression and pathogenesis of vulnerable plaques.

Abstract:Graft lesions after coronary artery bypass graft are the common phenomenon. Thrombosis, endothelial dysfunction, vasospasm, and oxidative stress are important mechanisms leading to the lesions. Compared with arterial bypass graft, venous bypass graft is more susceptible to lesions, which is closely related to the anatomical morphology and functional characteristics of veins themselves. Acute thrombosis, intimal hyperplasia and vulnerable plaque formation are important mechanisms of vein graft lesions during different stages. Secondary prevention drugs such as antiplatelet and lipid-lowering drugs can improve the patency rate of bypass grafts. The search for predictors and related gene pathways of vein graft disease is expected to provide new research directions for vein graft disease at cellular and molecular levels. The review summarizes the research progress on pathogenesis of vein bypass graft stenosis and new vulnerable plaque lesions after coronary artery bypass graft.

Abstract:Aim To study the effect of stable concentration and physicochemical parameters of chitosan (CS) and hyaluronic acid (HA) polyelectrolyte complex (PEC) nanoparticles in physiological saline on the adsorption of targeting antibody CD47 and the target of synthesized nanocarriers in vitro and in vivo. Methods Chitosan was used as a polycation and hyaluronic acid as a polyanion to charge neutralize, and chitosan and hyaluronic acid polyelectrolyte complex nanoparticles were synthesized. A model antibody, atherosclerosis targeting antibody CD47, was adsorbed on the surface of CS-HA nanoparticles after 4 h of action with nanoparticles in water or PBS. The synthesized nanocarriers interact with vascular endothelial cells and atherosclerotic plaques in vitro and in vivo to study their targeting effects. Results The complexation process and the physicochemical properties of the colloid were affected by external factors such as charge mixing ratio and polymer concentration. Non-stoichiometric CS-HA nanocolloids were synthesized by the above principles and remained stable in water or PBS (pH 7.4) solution for more than one month. Scanning electron microscopy was used to detect the morphology. The average particle size of CS-HA/CD47 antibody nanoparticles was between 375 and 620 nm, and the zeta potential was positive. The nanocarriers targeted by the CD47 antibody can be efficiently adsorbed to the surface of vascular endothelial cell lines and atherosclerotic plaques. Conclusions CS-HA/CD47 antibody nanoparticles were successfully synthesized in this experiment. The targeted nanocarriers can effectively adsorb to the surface of vascular endothelial cells and atherosclerotic plaques in vitro and in vivo. It is an effective nanocarrier with application prospects for targeted administration of atherosclerosis.

Abstract:Aim To analyze the changes of lipid metabolites in menopausal rats and identify potential biomarkers in metabolic changes. Methods 4-month-old female SD rats were randomly divided into sham operation (Sham) group and ovariectomized (OVX) group. Using UPLC/LTQ-Orbitrap-MS metabonomics analysis method, principal component analysis (PCA) and orthogonal-partial least squares analysis (OPLS-DA) were used for multivariate statistical analysis to screen potential biomarkers related to diseases. Results The OPLS-DA score plot could be used to distinguish the plasma lipid metabolites of rats in the sham group and ovariectomized group, and there was no significant overlap between the two groups. Compared with the sham group, the relative contents of ceramide (Cer), sphingomyelin (SM), platelet activating factor (PAF), lysophosphatidylcholine (LPC), triglyceride (TG) and omega-6 unsaturated fatty acid (ω-6PUFA) increased in the ovariectomized group, while the relative contents of diglyceride (DG), phosphatidylglycerin (PG) and phosphatidylserine (PS) decreased. A total of 35 endogenous metabolites were detected in both groups, including Cer, SM, PAF, LPC, TG, DG, PS, PG, ω-6PUFA as potential biomarkers. Conclusion All the 9 potential biomarkers were related to menopausal syndrome, which laid a foundation for the early detection of biomarkers of senile degenerative diseases.

Abstract:Aim To investigate the effects of acupuncture combined with Tangke apozem on transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-9 (MMP-9) and connective tissue growth factor (CTGF) in diabetic nephropathy rats. Methods 54 SPF SD male rats were selected, and 8 of them were randomly selected as control group. The remaining rats were subjected to diabetic nephropathy (DN) model replication, one-time rat tail vein injection of streptozotocin. Rats were randomly divided into model group, irbesartan group, acupuncture combined with Tangke apozem group (acupuncture combined with traditional Chinese medicine group), Tangke apozem treatment group (Chinese medicine group) and acupuncture group. Observe the general condition of the rats, and measure body weight, blood sugar, kidney weight/body weight, 24-hour urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), triglyceride (TG) and total cholesterol (TC); HE staining, Masson staining and glycogen staining (PAS) were used to observe changes in renal tissue morphology; The protein expression levels of TGF-β1, MMP-9, collagen Ⅰ, CTGF, and TIMP-1 in kidney tissues were detected by Western blot method. Results Compared with the model group, the weight, kidney weight/body weight ratio, 24 h urine protein, BUN, SCr, TG, TC of the acupuncture combined with traditional Chinese medicine group, Chinese medicine group and irbesartan group were significantly improved, and the combination of needle and medicine was more remarkable. The acupuncture group slightly improved. The expression levels of TGF-β1 and CTGF protein were significantly decreased. The expression of TIMP-1 was down-regulated by adjusting the protein expression of MMP-9, and the hydrolysis of Collafen Ⅰ was accelerated. The expression of TGF-β1, CTGF and TIMP-1 in the acupuncture combined with traditional Chinese medicine group was significantly lower than that in the traditional Chinese medicine or irbesartan group, and the expression of MMP-9 was increased. The acupuncture combined with traditional Chinese medicine group was more effective than the Chinese medicine group and the Western medicine group. Conclusions Acupuncture combined with Tangke apozem has obvious therapeutic effect compared with traditional Chinese medicine group. It can effectively regulate the expression of TGF-β1, MMP-9 and CTGF, reduce glomerular sclerosis, reduce proteinuria and prevent renal function, and protect DN lesions. The progress has been delayed.

Abstract:Aim To investigate the effect of alprostadil on myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods 160 STEMI patients who met the criteria from November 2017 to April 2018 in our hospital were selected as the study subjects. They were randomly divided into alprostadil group (80 cases) and control group (80 cases). Alprostadil group was treated with alprostadil on the basis of routine treatment in the control group. The indexes of myocardial reperfusion, such as thrombolysis in myocardial infarction (TIMI) blood flow grade, corrected TIMI frame count (CTFC), myocardial blush grade (MBG), ST-segment resolution (STR) more than or equal to 50% within 2 hours after PCI and no-reflow after PCI, were compared between the two groups. The levels of inflammatory indexes such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were detected in serum at admission and 7 days after PCI. Left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) of colour sonography were measured at 3 days after PCI and 3 months after discharge. Major adverse cardiac events (MACE) within 3 months after discharge were followed up. Results (1)The baseline data of the two groups were consistent and comparable. (2)The incidences of TIMI grade 3, MBG grade 3 after PCI and STR more than or equal to 50% within 2 hours after PCI in alprostadil group were higher than those in control group (P＜0.05), while the incidence of no-reflow and the number of CTFC frames were lower than those in control group (P＜0.05). (3)There were no significant differences in serum TNF-α, IL-6 and hs-CRP levels between the two groups on admission (P＞0.05). The serum levels of TNF-α, IL-6 and hs-CRP in alprostadil group were lower than those in control group on the 7th days after PCI (P＜0.01). (4)After 3 months follow-up, the LVEDD of the alprostadil group was lower than that of the control group and the LVEF was higher than that of the control group (P＜0.05). The incidences of total MACE and heart failure in the alprostadil group were lower than those in the control group (P＜0.05). Conclusion The application of alprostadil in STEMI patients undergoing primary PCI can effectively reduce inflammation, restore myocardial reperfusion, reduce the occurrence of myocardial microcirculation disorders, and improve cardiac function and prognosis.

Abstract:Aim To study the relationship between non-high density lipoprotein cholesterol levels and severity of coronary artery atherosclerosis. Methods This research studied 843 consecutive subjects undergoing coronary angiography who did not receive any lipid-lowering therapy. The severity of coronary artery atherosclerosis was determined using the Gensini score (GS)system. The patients were classified into the four groups according to the quartile of the GS. Then the patients were divided into three groups:the sigle-vessel group, the double-vessel group, the triple-vessel group.Lipid parameters were measured in all groups. The correlation analysis, receiver-operator characteristic and logistic regression analysis were performed, respectively. Results LDLC, non-HDLC and TC/HDLC were all dramatically increased according to the quartiles of GS (P<0.05, respectively), TG/HDLC in upper GS quartile was higher than the 1st and 2nd GS quartile. LDLC, non-HDLC, TC/HDLC in the double-vessel group, the triple-vessel group were significantly higher than those of the sigle-vessel group(P<0.05, respectively), TG/HDLC level had no significant difference. non-HDLC(r=0.315,P<0.01) was more closely related to GS than LDLC(r=0.252,P<0.01), TC/HDLC(r=0.242,P<0.01), TG/HDLC(r=0.123,P<0.01). The area under receiver operating characteristic curve(AUC) of non-HDLC for predicting high GS was 0.729(95%Cl 0.691～0.767,P<0.01) higher than LDLC's 0.694(95%Cl 0.653～0.734,P<0.01), TC/HDLC's 0.681(95%Cl 0.640～0.721,P<0.01), TG/HDLC's 0.564(95%Cl 0.521～0.607,P<0.01). Multivariate logistic regression analysis suggested that non-HDLC(OR=2.2,5%Cl 1.962～3.115) was slightly superior to LDLC(OR=2.5,5%Cl 1.785～2.875), TC/HDLC(OR=1.6,5%Cl 1.483～2.175), TG/HDLC(OR=1.022, 95%Cl 0.927～1.127) in predicting high GS after adjusting for potential confounders. Conclusion non-HDLC levels is a better predictor for the coronary atherosclerosis severity compared with LDLC, TC/HDLC, TG/HDLC.

Abstract:Aim To discuss the safety and curative efficiency of excimer laser ablation (ELA) combined with drug-coated balloon(DCB) angioplasty treating in-stent restenosis(IRS) of femoral-popliteal artery. Methods This study retrospectively analyzed all 36 clinical data of patients whose femoral-popliteal artery has IRS and treated by excimer laser ablation (ELA) combined with plain old balloon angioplasty(POBA) and DCB angioplasty between March 2017 to Feburary 2018. 36 patients were treated as the observation group, and 57 patients whose treatment is POBA combined with DCB angioplasty were treated as control group. Observe the success rate of surgery, complication rate, minimum lumen diameter (MLD) immediately after surgery, ankle brachial index(ABI) in the third day after surgery etc. Postoperatively follow up ABI in the first, third, sixth, twelfth month after surgery, target lesion revascularization(TLR) rate in twelve months, ISR, amputation rate, MLD, late lumen loss(LLL) etc. Results There was no significant difference between the two groups in terms of gender, age, TASCII grade, and other comorbidities (P>0.05). It analyzed the ABI at 1,3, 6 and 12 months after operation, and the TLR, ISR, amputation rate, MLD and LLL at 12 months after operation.The P values were all less than 0.05, and the observation group was superior to the control group. Conclusion ELA combined with POBA and DCB is safe and effective in the treatment of femoral-popliteal artery ISR, with short and moderate-term effect better than POBA combined with DCB.

Abstract:Aim To explore the predictive value of cumulative blood pressure exposure (cumBP) for new-onset atrial fibrillation (AF). Methods A prospective cohort study was used in this study. The people of Kailuan Group, Tangshan, were observed every two years since 2006. By the end of 2015, five examinations were carried out. The number of participants in the first three physical examinations with complete blood pressure and other baseline data was 57927. 40727 subjects were included in the final statistical analysis, excluding the patients with previous AF history and missing electrocardiogram data during follow-up. According to cumulative systolic blood pressure exposure (cumSBP), four quantiles grouping was performed:first quartile group:cumSBP＜464 mmHg·year; second quartile group:464 mmHg·year≤cumSBP＜512 mmHg·year; third quartile group:512 mmHg·year≤cumSBP＜569 mmHg·year; fourth quartile group:cumSBP≥569 mmHg·year. The status of new-onset AF was compared in different cumSBP groups. COX proportional hazard model was used to analyze the predictive value of cumBP for new-onset AF. Results (1)In 40727 cases, the average age was 51.81±11.54 years old, among them, there were 30693 males (75.4%) and 10034 females (24.6%). (2)The results showed that the proportion of men and the levels of age, body mass index, fasting blood glucose, total cholesterol and uric acid increased with the increase of cumSBP, and the differences among the groups were statistically significant (P＜0.05). (3)The average follow-up period was 4.97±0.37 years. The analysis of the multivariate COX proportional hazard model affecting the new-onset AF showed that, after correcting other confounding factors, the HR value of new-onset AF was 1.034 (95%CI 1.012-1.057) for every 10 mmHg·year increase in cumSBP, and HR value was 1.026 (95%CI 1.008-1.044) for every 5 mmHg·year increase in cumulative diastolic pressure exposure. Conclusion Cumulative blood pressure exposure has predictive value for new-onset atrial fibrillation.

Abstract:Coronary heart disease (CHD) and its complications are the most important risk factors for human mortality, so the research on the prevention and treatment of CHD has been paid more and more attention in academic circles.A large number of studies have shown that the main pathological process of CHD is the destruction of lipid metabolism balance and the activation of inflammatory response. It will provide an effective method for clinical diagnosis of CHD if we can summarize the changes of related protein expression in the course of CHD. The discovery of new biomarkers is of great significance for the prevention and treatment of CHD. In recent years, a large number of biomarkers which are closely related to cardiovascular diseases have been discovered. Novel lipid-related biomarkers such as proprotein convertase subtilisin/kexin 9 and sortilin participates in the occurrence and development of CHD by regulating the level of oxidized low density lipoprotein cholesterol. Inflammatory markers such as soluble urokinase plasminogen activated receptor affect the pathophysiological process of CHD through a variety of pathways. Therefore, this article mainly reviews the research progress of blood lipids, inflammation and other related new biomarkers in CHD, in order to provide a new reference and ideas for the clinical diagnosis, treatment and prognosis evaluation of cardiovascular disease.

Abstract:Dyslipidemia is a major risk factor for cardiovascular disease, especially elevated low density lipoprotein cholesterol (LDLC) significantly increases the incidence of atherosclerotic cardiovascular disease (ASCVD). Statins have shown to be effective in reducing serum LDLC, thereby reducing the risk of ASCVD. However, in the course of clinical application of statins, more and more studies show that statins have drug resistance. Studies have shown that statin resistance is mainly affected by drug absorption, transport, metabolism and drug action itself. Intensive study of statin resistance can provide theoretical basis for further revealing the action mechanism of statins, and hopefully provide a target for the development of new lipid-lowering drugs.