The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases.

Exosomes, mainly derived from mesenchymal stem cells, provide a good reference for cardiac function repair and clinical application in cardiac and vascular diseases by regulating cardiomyocyte viability, inflammatory levels, angiogenesis, and ventricular remodeling after a heart injury. This review presents the cardioprotective efficacy of mesenchymal stem cell-originated exosomes and explores the underlying molecular mechanisms. Furthermore, we expound on several efficient approaches to transporting exosomes into the heart in clinical application and comment on the advantages and disadvantages of each method.

The Chains of Ferroptosis Interact in the Whole Progression of Atherosclerosis.

Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation.

BACKGROUND AND AIMS: Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms. METHODS: SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue. RESULTS: BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment. CONCLUSIONS: BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.

Monocyte-to-high-density lipoprotein ratio as a predictor for patients with Takayasu arteritis and coronary involvement: a double-center, observational study.

Background: The implication of the monocyte-to-high-density lipoprotein ratio (MHR) in Takayasu arteritis (TAK) remains unclear. Objective: We aimed to assess the predictive value of the MHR to identify coronary involvement with TAK and determine the patient prognosis. Methods: In this retrospective study, 1,184 consecutive patients with TAK were collected and assessed, and those who were initially treated and with coronary angiography were enrolled and classified according to coronary involvement or no involvement. Binary logistic analysis was performed to assess coronary involvement risk factors. Receiver-operating characteristic analysis was used to determine the MHR value to predict coronary involvement in TAK. Major adverse cardiovascular events (MACEs) were recorded in patients with TAK and coronary involvement within a 1-year follow-up, and Kaplan-Meier survival curve analysis was conducted to compare MACEs between them stratified by the MHR. Results: A total of 115 patients with TAK were included in this study, and 41 of them had coronary involvement. A higher MHR was found for TAK with coronary involvement than for TAK without coronary involvement (P = 0.014). Multivariate analysis showed that the MHR is an independent risk factor for coronary involvement in TAK (odds ratio: 92.718, 95% confidence interval (CI): 2.813-3056.291, P = 0.011). With the best cut-off value of 0.35, the MHR identified coronary involvement with 53.7% sensitivity and 68.9% specificity [area under the curve (AUC): 0.639, 95% CI: 0.544-0.726, P=0.010] and identified left main disease and/or three-vessel disease (LMD/3VD) with 70.6% sensitivity and 66.3% specificity (AUC: 0.704, 95% CI: 0.612-0.786, P = 0.003) in TAK. Combined with other variables, the MHR identified coronary involvement with 63.4% sensitivity and 90.5% specificity (AUC: 0.852, 95% CI: 0.773-0.911, P < 0.001), and identified LMD/3VD with 82.4% sensitivity and 78.6% specificity (AUC: 0.827, 95% CI: 0.720-0.934, P < 0.001) in TAK. A total of 39 patients with TAK and coronary involvement were followed up for 1 year, and 5 patients suffered a MACE. Those with an MHR >0.35 had a higher MACE incidence than their counterparts with an MHR ≤0.35 (χ2 = 4.757, P = 0.029). Conclusions: The MHR could be a simple, practical biomarker for identifying coronary involvement and LMD/3VD in TAK and predicting a long-term prognosis.

The cGAS-STING Pathway: A Ubiquitous Checkpoint Perturbing Myocardial Attributes.

As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.

cGAS-STING Pathway Performance in the Vulnerable Atherosclerotic Plaque.

The important role of Ca2+ in pathogenic store-operated calcium entry (SOCE) is well-established. Among the proteins involved in the calcium signaling pathway, Stromal interacting molecule 1 (STIM1) is a critical endoplasmic reticulum transmembrane protein. STIM1 is activated by the depletion of calcium stores and then binds to another calcium protein, Orai1, to form a channel through which the extracellular Ca2+ can enter the cytoplasm to replenish the calcium store. Multiple studies have shown that increased STIM1 facilitates the aberrant proliferation and apoptosis of vascular smooth cells (VSMC) and macrophages which can promote the formation of rupture-prone plaque. Together with regulating the cytosolic Ca2+ concentration, STIM1 also activates STING through altered intracellular Ca2+ concentration, a critical pro-inflammatory molecule. The cGAS-STING pathway is linked with cellular proliferation and phenotypic conversion of VSMC and enhances the progression of atherosclerosis plaque. In summary, we conclude that STIM1/cGAS-STING is involved in the progression of AS and plaque vulnerability.

Comparison of clinical profiles and associated factors for acute myocardial infarction among young and very young patients with coronary artery disease.

BACKGROUND: This study aimed to compare the profiles of young and very young patients with coronary artery disease (CAD) and explore the factors associated with acute myocardial infarction (AMI) based on age. METHODS: Young CAD patients aged between 18 and 44 years diagnosed by angiography were enrolled retrospectively. They were divided into two groups according to age: young CAD was defined as patients aged between 36 and 44 years, and very young CAD was defined as patients aged between 18 and 35 years. Demographic and clinical characteristics of the patients were collected. RESULTS: In total, 9286 patients were included in the final database. Most were assigned to the young CAD group (86.5%), and 1250 (13.5%) had very young CAD. Most demographic and clinical characteristics of the young and very young patients with CAD differed significantly. The proportion of patients with CAD in the total population increased with age, whereas the incidence of AMI showed a decreasing trend. A previous percutaneous coronary intervention (PCI) was negatively associated with AMI. Dyslipidemia, current smoking, and hyperhomocysteinemia were positively associated with AMI in the overall and young population with CAD. CONCLUSIONS: The clinical profiles and factors associated with AMI in CAD patients of different ages were significantly different. Lifestyle-related factors were significantly associated with AMI in young patients with CAD.

Effectiveness of Integrative Medicine Therapy on Coronary Artery Disease Prognosis: A Real-World Study.

OBJECTIVE: To evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting. METHODS: A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group); or conventional treatment alone (CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction (MI), and revascularization]. RESULTS: A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% (514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ⩾ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ⩾ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), ß-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ⩾ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218). CONCLUSION: In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Hypersensitivity to ticagrelor and low response to clopidogrel: a case report.

Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin.

Level of Pregnancy-associated Plasma Protein-A Correlates With Coronary Thin-cap Fibroatheroma Burden in Patients With Coronary Artery Disease: Novel Findings From 3-Vessel Virtual Histology Intravascular Ultrasound Assessment.

Pregnancy-associated plasma protein-A (PAPP-A) level is an independent predictor of acute cardiovascular event occurrence. To test the hypothesis that increased PAPP-A levels would be associated with a higher burden of coronary thin-cap fibroatheroma (TCFA) thereby underlying the heightened risk for cardiovascular events in patients with coronary artery disease; 154 patients (462 vessels and 975 plaques) with stable angina or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) referred for percutaneous coronary intervention were assessed using 3-vessel virtual histology (VH)-intravascular ultrasound (IVUS). Thin-cap fibroatheroma virtual histology was defined as focal, necrotic core (NC)-rich (≥10% of cross-sectional area) plaques in contact with the lumen, and plaque burden ≥40%. Pregnancy-associated plasma protein-A levels were determined by sandwich enzyme-linked immunosorbent assay, and patients were divided into 3 groups based on PAPP-A level tertiles. Although the highest PAPP-A level tertile was not associated with 3-vessel plaque number, it was associated with 3-vessel VH-TCFA number and necrotic core volume. Patients with ≥3 VH-TCFAs had a higher PAPP-A level than patients with 1 to 3 VH-TCFAs or without any VH-TCFA (13.3 ±â€Š11.8 versus 7.8 ±â€Š4.7 versus 7.4 ±â€Š4.7 mIU/L, P < 0.001, respectively). Moreover, PAPP-A level was an independent predictor of higher total number of VH-TCFAs (OR 1.18; 95% CI 1.07-1.29, P = 0.001). This VH-IVUS study demonstrated, for the first time to our knowledge, that higher PAPP-A levels are associated with higher 3-vessel TCFA burden in patients with coronary artery disease. Pregnancy-associated plasma protein-A, therefore, might be a useful serum biomarker to predict increased coronary TCFA burden and plaque instability.

[Effect and mechanism of recombinant hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice].

OBJECTIVE: To explore the effect and mechanism of hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Totally 24 ApoE(-/-) mice, 7-8 weeks old were fed with high fat diets. They were randomly divided into the recombinant hirudin treatment group (drug group) and the model group according to body weight and different dens, 12 in each group. Twelve C57BL/6J mice, 7-8 weeks old fed with high fat diet were recruited as the normal control group. Recombinant hirudin (0.25 mg/kg) was intraperitoneally injected to mice in the drug group from the 10th week old once every other day for five successive weeks. Equal volume of normal saline was injected to mice in the model group. Mice in the normal control group received no treatment. All mice were sacrificed after fed with high fat diet until they were 20 weeks old. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), E-selectin, interleukin-6 (IL-6), and stromal metalloproteinase-2 (MMP-2) were detected. The plaque/lumen area and extracellular lipid composition/ plaque area were analyzed by HE staining and morphometry. Changes of signaling molecules in store-operated calcium channels, including stromal interacting molecule 1 (STIM1), Orail protein, and transient receptor potential channel 1 (TRPC1) were determined by Western blot. Results Lipid plaque formed in the aorta vessel wall of 20-week old mice in the model group. Compared with the normal control group, serum levels of TC, TG and LDL increased (P<0.01), hs-CRP, E-selction, IL-6, and MMP-2 obviously increased (P<0.01, P<0.05) in the model group; expression levels of STIM1, TRPC1, and Orail significantly increased (P<0.01). Compared with the model group, the plaque/lumen area and the extracellular lipid composition/plaque area significantly decreased in the drug group (P<0.05, P<0.01); serum levels of TC and LDL, hs-CRP, E-selction, IL-6, and MMP-2 obviously decreased (P<0.05, P<0.01); expression levels of STIM1, TRPC1, and Orail were significantly down-regulated (P<0.05, P<0.01). CONCLUSION: Hirudin could significantly improve lipids and endothelial functions of ApoE(-/-) mice, down-regulate expression levels of STIM1, Orai1, and TRPC1, and thus delaying the occurrence and development of atherosclerosis.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Clinical effect of Maixuekang Capsule (脉血康胶囊) on long-term prognosis in patients with acute coronary syndrome after percutaneous coronary intervention.

OBJECTIVE: To study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (, MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention (PCI). METHODS: A total of 236 patients with acute coronary syndrome, who received successful PCI, were randomly assigned to a trial group (116 cases) and a control group (120 cases) according to random numbers; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms. In the trial group, the patients were treated with MKC combined with routine medication, and in the control group the patients were treated with routine medication. The therapeutic course for the two groups was 12 months and the follow-up was 12 months. The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein (hs-CRP) were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up. RESULTS: Compared with before PCI, the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI (P<0.05). They were significantly reduced after 30-day-treatment of MKC, showing statistical differences when compared with those in the control group (P<0.05). During the 12-month follow-up, the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group (6.9% vs. 12.5%, P<0.01). CONCLUSIONS: ADP-induced platelet aggregation function was significantly elevated after PCI. MKC improved the prognosis of patients with acute coronary syndrome, possibly through inhibiting the platelet aggregation, fighting against inflammation, and protecting the vascular endothelial function.

[Effects of Maixuekang Capsule on the platelet aggregation rate and its long-term prognosis of patients with acute coronary syndrome under percutaneous coronary intervention].

OBJECTIVE: To study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (MC) on the platelet aggregation rate, high-sensitive C-reactive protein (hs-CRP) and the long-term prognosis in patients with acute coronary syndrome under percutaneous coronary intervention (PCI). METHODS: Totally 236 inpatients with acute coronary syndrome under PCI, who successively received PCI from July 2008 to June 2010, were randomly assigned to the routine treatment group (RTT, 120 cases) and the MC treatment group (MKT, 116 cases). Besides routine medication, patients in the MKT group additionally took MC, 12 capsules daily for 12 successive months. The ADP-induced platelet aggregation rate and hs-CRP concentration were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of adverse cardio-/cerebrovascular events was recorded during the twelve-month clinical follow-up. Results Compared with before PCI, ADP-induced platelet aggregation rate and the serum hs-CRP concentration were significantly higher 12 h after PCI (P < 0.05). They were significantly reduced after 30-day treatment of MC, showing statistical difference when compared with those in the RTT group (P < 0.05). In the 12-month follow-up, the incidence of adverse cardio-/cerebrovascular events was significantly lower in the MKT group than in the RTT group (6.9% vs 12.5%, P < 0.01). CONCLUSIONS: ADP-induced platelet aggregation function was significantly elevated after PCI, which was a predictive factor of poor coronary events. MC improved the long-term prognosis of patients with acute coronary syndrome possibly through inhibiting the platelet aggregation rate and the hs-CRP concentration.

Combined effect of atorvastatin and probucol on plasma cystatin C levels and severity of coronary lesion in patients with borderline coronary lesion.

BACKGROUND: The plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions. METHODS: One hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography. RESULTS: PcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment. CONCLUSIONS: Cystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes.

BACKGROUND: It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes. METHODS: The ß-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed. RESULTS: The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced ß-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05). CONCLUSIONS: Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is related to the characteristics of microbubbles.

[Evaluation on the relationship between pregnancy associated plasma protein-a and intravascular ultrasound detected culprit coronary plaque morphology in patients with unstable angina].

OBJECTIVE: To assess the relationship between pregnancy associated plasma protein-A (PAPP-A) and culprit coronary plaque morphology in patients with unstable angina (UA). METHODS: Sixty-eight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study. A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A. Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels. RESULTS: PAPP-A level was significantly higher in high-risk UA than in non-high-risk UA [(19.9 ± 20.1) mIU/L vs. (6.9 ± 5.7) mIU/L, P = 0.002]. Optimal threshold of PAPP-A to predict high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6% and a specificity of 77.5%. Patients with higher PAPP-A level (≥ 11.0 mIU/L) was associated with larger external elastic membrane cross-sectional area, plaque area and more plaque burden compared with patients with lower PAPP-A level (all P < 0.01). Positive remodeling, attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level (all P < 0.01). PAPP-A ≥ 11.0 mIU/L (OR = 5.921, P = 0.014) and attenuated plaque (OR = 7.541, P = 0.038) were independent risk predictors for high-risk UA. CONCLUSIONS: PAPP-A was associated with instability of culprit plaque in UA patients. PAPP-A ≥ 11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.

Long-term (4-year) outcomes and predictors of adverse cardiac events after sirolimus-eluting stent implantation in unprotected left main coronary artery.

The long-term safety and efficiency of sirolimus-eluting stent (SES) treatment in unprotected left main coronary artery (ULMCA) have not yet been ascertained.From 2003 to 2006, 126 consecutive patients with de novo lesions in ULMCA who underwent SES were retrospectively analyzed in a single center in China. During 4-year follow-up, major adverse cardiovascular event (MACE)-free survival was 74.6%. Cardiac death occurred in 5 (4.0%), and target lesion revascularization (TLR) and target vessel revascularization (TVR) occurred in 15 (11.9%) and 24 (19.0%) patients, respectively. One (0.8%) experienced probable stent thrombosis while 1 (0.8%) presented possible stent thrombosis. Impaired LVEF (< 40%) and high surgical risk (Euro score > 6) were the independent predictors of MACEs.PCI with SES for de novo lesions in ULMCA is feasible with a low procedural risk. However, SES was associated with a relatively higher rate of TLR and TVR. Impaired LVEF and high surgical risk were important predictors of MACEs.

[Efficacy of stents coated with antibody against CD105 on preventing restenosis and thrombosis in minipigs].

OBJECTIVE: Novel stents loaded with antibody against CD105 were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting activated endothelial cell. METHODS: Thirty Stents coated with antibody against CD105, thirty unloaded polymer, and thirty bare metal stents were deployed in 90 coronary arteries of 30 minipigs. Oral aspirin (300 mg before operation and 100 mg post operation) and clopidogrel (300 mg before operation and 75 mg post operation) were orally administrated. Coronary artery quantitative analysis was completed by coronary arteriography, the vascular endothelium changes were observed under scanning electron microscope and the vascular morphological changes were observed under light microscope 7 and 14 days after operation. RESULTS: Complete procedural and angiographic success was achieved in all 30 minipigs. There were no major adverse cardiac and cerebrovascular events. At 7 days, there was no difference for mean neointimal area and percent area stenosis among various groups. At 14 days, endothelialization scores were significantly higher in the CD105 antibody-loaded stents and bare metal stents group than in sirolimus-eluting stents group (1.78 ± 0.49, 1.50 ± 0.67 vs. 1.08 ± 0.29, all P < 0.05), mean percent area stenosis in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(23.8 ± 4)%, (24.2 ± 2)% vs. (38.0 ± 3)%, all P < 0.05], mean angiographic late luminal loss in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(0.29 ± 0.28) mm, (0.28 ± 0.02) mm vs. (0.41 ± 0.01) mm, all P < 0.05]. There was no difference for mean percent area stenosis in the CD105 antibody-loaded stents and sirolimus-eluting stents group. The mean neointimal area in the CD105 antibody-loaded stents, and sirolimus-eluting stents group were less than that in bare metal stents group [(0.88 ± 0.08) mm(2), (0.89 ± 0.12mm)(2) vs. (1.00 ± 0.14) mm(2), all P < 0.05] and there was no difference for the mean neointimal area in the CD105 antibody-loaded stents and sirolimus-eluting stents group. At 7 and 14 days, there was no difference for the injury score and the inflammation score among various groups, scanning electron microscopy evidenced enhanced endothelial coverage on CD105 antibody-loaded stents compared to sirolimus-eluting stents group. CONCLUSION: Stent coated with antibody against CD105 could effectively reduce in-stent restenosis and accelerate endothelialization in the minipigs.