KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Four single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in <it>KCNQ1 </it>are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent. We investigated whether these 4 genetic markers are associated with serum lipid metabolism in a middle-aged Chinese Han population.</p> <p>Methods</p> <p>We enrolled 398 consecutive patients, including 180 with premature coronary artery disease (CAD) (male < 55 years, female < 65 years) and 218 controls without documented CAD. All subjects were genotyped for 4 SNPs by using the ligase detection reaction method. Fasting blood sugar (FBS) and plasma concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(apo A1), and apolipoprotein B (apo B) were determined by standard biochemical methods. Main anthropometric and metabolic characteristics are analyzed among 3 genotypes at rs2283228, rs2237895, rs2237897, or rs2237892 in <it>KCNQ1</it>.</p> <p>Results</p> <p>The 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, and TT were present in rs2237897 and rs2237892. The minor genotypes CC at rs2283228 and TT at rs2237892 were associated with higher levels of TG (<it>P </it>= 0.007 and 0.026, respectively). Furthermore, subjects with the CC genotype at rs2283228 had lower levels of HDL-C and apo A1 than in the other 2 genotype groups (<it>P </it>= 0.052 and 0.055, respectively). No other associations were detected between these 4 SNPs and FBS or other lipid parameters.</p> <p>Conclusions</p> <p>Our data suggest that rs2283228 and rs2237892 in <it>KCNQ1 </it>are associated with lipid metabolism in a middle-aged Chinese Han population.</p

Dual-modal tracking of transplanted mesenchymal stem cells after myocardial infarction

Yefei Li*, Yuyu Yao*, Zulong Sheng, Yanxiaoxiao Yang, Genshan Ma,Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China*These two authors contributed equally to this work.Purpose: Results for implantation efficiency and effective improvement of cardiac function in the field of mesenchymal stem cells (MSCs) are controversial. To attempt to clarify this debate, we utilized magnetic resonance imaging (MRI) and near-infrared optical imaging (OI) to explore the effects of different delivery modes of mesenchymal stem cells on cell retention time and cardiac function after myocardial infarction (MI).Methods: Rat MSCs were labeled with superparamagnetic iron oxide nanoparticles and 1, 1&amp;prime;-dioctadecyl-3,3,3&amp;prime;,3&amp;prime;-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (DiD) for noninvasive cell tracking in a rat MI model. Rats underwent coronary artery ligation and were randomized into three experimental groups: intravenous (IV), intramyocardial (IM), and a control group. The first two groups referred to the route of delivery of the transplanted dual-labeled MSCs; whereas the control group was given an IV injection of serum-free medium one day post-MI. Cellular engraftment was determined 1 day and 7 days post cell delivery by measuring the iron and optical signals in explanted organs. Prussian blue staining and fluorescent microscopy were performed on histological sections for iron and DiD, respectively. Cardiac function was measured by echocardiography on day 7.Results: The cardiac function of the IM group increased significantly compared to the IV and control groups at day 7. In the IM group, labeled cells were visualized in the infracted heart by serial MRI, and the intensity by OI was significantly higher on day 1. In the IV group, the heart signals were significantly attenuated by dual-modal tracking at two time points, but the lung signals in OI were significantly stronger than the IM group at both time points.Conclusion: IM injection of MSCs increased cell engraftment within infarcted hearts and improved cardiac function after MI. However, IV infusion has a low efficacy due to the cell trapping in the lung. Therefore, direct injection may provide an advantage over IV, with regard to retention of stem cells and protection of cardiac function.Keywords: stem cell tracking, superparamagnetic iron oxide, DiD, cardiac function, myocardial infarctio

Clinical Implication of Coronary Tortuosity in Patients with Coronary Artery Disease

Background: Coronary tortuosity (CT) is a common coronary angiography finding. The exact pathogenesis, clinical implication and long-term prognosis of CT are not fully understood. The purpose of this study is to investigate the clinical characteristics of CT in patients with suspected coronary artery disease(CAD) in a Chinese population. Methods: A total of 1010 consecutive patients underwent coronary angiography with complaints of chest pain or related symptoms were included in the present study (544 male, mean age: 64611 years). CT was defined by the finding of $3 bends (defined as$45u change in vessel direction) along main trunk of at least one artery in systole and in diastole. Patients with or without CAD were further divided into CT-positive and CT-negative groups, all patients were followed up for the incidence of major adverse cardiovascular events (MACE) for 2 to 4 years. Results: The prevalence of CT was 39.1 % in this patient cohort and incidence of CT was significantly higher in female patients than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P,0.001). CT was positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131, 2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574, 0.994, P = 0.045). MACE during follow up was similar between CAD patients with or without CT. Conclusions: CT is more often seen in females and positively correlated with hypertension and negatively correlated wit

Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: An IVUS-based fluid-structure interaction multi-patient study

BACKGROUND: Atherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions. METHODS: IVUS data were acquired from 10 patients after voluntary informed consent. The X-ray angiogram was obtained prior to the pullback of the IVUS catheter to determine the location of the coronary artery stenosis, vessel curvature and cardiac motion. Cyclic bending was specified in the model representing the effect by heart contraction. 3D anisotropic FSI models were constructed and solved to obtain flow shear stress (FSS) and plaque wall stress (PWS) values. FSS and PWS values were obtained for statistical analysis. Correlations with p < 0.05 were deemed significant. RESULTS: Nine out of the 10 patients showed positive correlation between wall thickness and flow shear stress. The mean Pearson correlation r-value was 0.278 ± 0.181. Similarly, 9 out of the 10 patients showed negative correlation between wall thickness and plaque wall stress. The mean Pearson correlation r-value was -0.530 ± 0.210. CONCLUSION: Our results showed that plaque vessel wall thickness correlated positively with FSS and negatively with PWS. The patient-specific IVUS-based modeling approach has the potential to be used to investigate and identify possible mechanisms governing plaque progression and rupture and assist in diagnosis and intervention procedures. This represents a new direction of research. Further investigations using more patient follow-up data are warranted

Sustained Release of IGF-1 by 3D Mesoporous Scaffolds Promoting Cardiac Stem Cell Migration and Proliferation

Background/Aims: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process. Methods: The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N2 adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays. Results: In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation. Conclusion: This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation

Impact of calcification on Murray law-based quantitative flow ratio for physiological assessment of intermediate coronary stenoses

Background: To investigate the influence of coronary calcification on the diagnostic performance of Murray law-based quantitative flow ratio (μQFR) in identifying hemodynamically significant coronary lesions referenced to fractional flow reserve (FFR). Methods: A total of 571 intermediate lesions from 534 consecutive patients (66.1 ± 10.0 years, 67.2% males) who underwent coronary angiography and simultaneous FFR measurement were included. Calcific deposits were graded by angiography as none or mild (spots), moderate (involving ≤ 50% of the reference vessel diameter), and severe (&gt; 50%). Performance of μQFR to detect functional ischemia (FFR ≤ 0.80) was evaluated, including diagnostic parameters and areas under the receiver-operating curves (AUCs). Results: The discrimination of ischemia by μQFR was comparable between none/mild and moderate/severe calcification (AUC: 0.91 [95% confidence interval: 0.88–0.93] vs. 0.87 [95% confidence interval: 0.78–0.94]; p = 0.442). No statistically significant difference was observed for μQFR between the two categories in sensitivity (0.70 vs. 0.69, p = 0.861) and specificity (0.94 vs. 0.90, p = 0.192). Moreover, μQFR showed significantly higher AUCs than quantitative coronary angiographic diameter stenosis in both vessels with none/mild (0.91 vs. 0.78, p &lt; 0.001) and moderate/severe calcification (0.87 vs. 0.69, p &lt; 0.001). By multivariable analysis, there was no association between calcification and μQFR-FFR discordance (adjusted odds ratio: 1.529, 95% confidence interval: 0.788–2.968, p = 0.210) after adjustment for other confounding factors. Conclusions: μQFR demonstrated robust and superior diagnostic performance for lesion-specific ischemia compared with angiography alone regardless of coronary calcification

Quantification of patient-specific coronary material properties and their correlations with plaque morphological characteristics: An in vivo IVUS study

BACKGROUND: A method using in vivo Cine IVUS and VH-IVUS data has been proposed to quantify material properties of coronary plaques. However, correlations between plaque morphological characteristics and mechanical properties have not been studied in vivo. METHOD: In vivo Cine IVUS and VH-IVUS data were acquired at 32 plaque cross-sections from 19 patients. Six morphological factors were extracted for each plaque. These samples were categorized into healthy vessel, fibrous plaque, lipid-rich plaque and calcified plaque for comparisons. Three-dimensional thin-slice models were constructed using VH-IVUS data to quantify in vivo plaque material properties following a finite element updating approach by matching Cine IVUS data. Effective Young\u27s moduli were calculated to represent plaque stiffness for easy comparison. Spearman\u27s rank correlation analysis was performed to identify correlations between plaque stiffness and morphological factor. Kruskal-Wallis test with Bonferroni correction was used to determine whether significant differences in plaque stiffness exist among four plaque groups. RESULT: Our results show that lumen circumference change has a significantly negative correlation with plaque stiffness (r = -0.7807, p = 0.0001). Plaque burden and calcification percent also had significant positive correlations with plaque stiffness (r = 0.5105, p \u3c 0.0272 and r = 0.5312, p \u3c 0.0193) respectively. Among the four categorized groups, calcified plaques had highest stiffness while healthy segments had the lowest. CONCLUSION: There is a close link between plaque morphological characteristics and mechanical properties in vivo. Plaque stiffness tends to be higher as coronary atherosclerosis advances, indicating the potential to assess plaque mechanical properties in vivo based on plaque compositions

Accuracy of triggering receptor expressed on myeloid cells 1 in diagnosis and prognosis of acute myocardial infarction: a prospective cohort study

Background Acute myocardial infarction (AMI) is one of the fatal cardiac emergencies. The detection of triggering receptor expressed on myeloid cells 1 (TREM1), a cell surface immunoglobulin that amplifies pro-inflammatory responses, screened by bioinformatics was shown to be significant in diagnosing and predicting the prognosis of AMI. Methods GSE66360, GSE61144 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between AMI and control groups using R software. A total of 147 patients in total were prospectively enrolled from October 2018 to June 2019 and divided into two groups, the normal group (n = 35) and the AMI group (n = 112). Plasma was collected from each patient at admission and all patients received 6-month follow-up care. Results According to bioinformatic analysis, TREM1 was an important DEG in patients with AMI. Compared with the normal group, TREM1 expression was markedly increased in the AMI group (p < 0.001). TREM1 expression was positively correlated with fasting plasma glucose (FPG), glycosylated hemoglobin (HbAC), and the number of lesion vessels, although it had no correlation with Gensini score. TREM1 expression in the triple-vessels group was significantly higher than that of the single-vessel group (p < 0.05). Multiple linear regression showed that UA and HbAC were two factors influencing TREM1 expression. The ROC curve showed that TREM1 had a diagnostic significance in AMI (p < 0.001), especially in AMI patients without diabetes. Cox regression showed increased TREM1 expression was closely associated with 6-month major adverse cardiac events (MACEs) (p < 0.001). Conclusions TREM1 is a potentially significant biomarker for the diagnosis of AMI and may be closely associated with the severity of coronary lesions and diabetes. TREM1 may also be helpful in predicting the 6-month MACEs after AMI

High-density lipoprotein cholesterol to apolipoprotein A-1 ratio is an important indicator predicting in-hospital death in patients with acute coronary syndrome

Background: Dyslipidemia plays a pivotal role in the pathogenesis of acute coronary syndrome (ACS). This study aims to investigate the value of two indices associated with lipid metabolism, low-density lipoprotein cholesterol to apolipoprotein B ratio (LBR) and high-density lipoprotein cholesterol to apolipoprotein A-1 ratio (HAR), to predict in-hospital death in patients with ACS. Methods: This single-center, retrospective, observational study included 3,366 consecutive ACS patients in Zhongda Hospital, Southeast University from July 2013 to January 2018. The clinical and laboratory data were extracted, and the in-hospital death and hospitalization days were also recorded. Results: All patients were equally divided into four groups according to quartiles of HAR: Q1 (HAR &lt; 1.0283), Q2 (1.0283 ≤ HAR &lt; 1.0860), Q3 (1.0860 ≤ HAR &lt; 1.1798), and Q4 (HAR ≥ 1.1798). Overall, HAR was positively associated with the counts of neutrophils and monocytes, whereas negatively correlated to lymphocyte counts. HAR was negatively correlated to left ventricular ejection fraction (LVEF). Compared to other three groups, in-hospital mortality (vs. Q1, Q2, and Q3, p &lt; 0.001) and hospitalization length (vs. Q1, Q2, and Q3, p &lt; 0.001) were significantly higher in the Q4 group. When grouped by LBR, however, there was no significant difference in LVEF, in-hospital mortality, and hospitalization length among groups. After adjusting potential impact from age, systolic blood pressure, creatine, lactate dehydrogenase, albumin, glucose, and uric acid, multivariate analysis indicated that HAR was an independent factor predicting in-hospital death among ACS patients. Conclusions: HAR had good predictive value for patients’ in-hospital death after the occurrence of acute coronary events, but LBR was not related to in-hospital adverse events