Total leukocyte counts in men and women in different age groups.

<p>Data shown are mean ± standard error of mean in men and women, respectively, in each age group; *indicates p<0.05 comparing men and women in the respective age group.</p

Counts and percentages of neutrophil and lymphocyte, and neutrophil-to-lymphocyte ratio, in men and women in different age groups.

<p>Data shown are mean ± standard error of mean in men and women, respectively, in each age group; *indicates p<0.05 comparing men and women in the respective age group.</p

Counts and percentages of monocyte, eosinophil and basophil in men and women in different age groups.

<p>Data shown are mean ± standard error of mean in men and women, respectively, in each age group; *indicates p<0.05 comparing men and women in the respective age group.</p

Subcutaneous Injection of Nitroglycerin at the Radial Artery Puncture Site Reduces the Risk of Early Radial Artery Occlusion After Transradial Coronary Catheterization: A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Transradial coronary catheterization is widely used as a diagnostic or interventional procedure for coronary disease. However, it can lead to adverse complications, such as radial artery occlusion. We sought to determine whether preprocedural injection of nitroglycerin at the radial artery puncture site reduces radial artery occlusion. METHODS AND RESULTS: A total of 188 patients undergoing transradial coronary catheterization were randomized in a single-blind fashion to receive subcutaneous injection of 0.5 mL 0.1% nitroglycerin or a placebo at the radial artery puncture site. The participants underwent ultrasound examinations of the radial artery before and at 24 hours after the procedure. Of the 188 patients enrolled, 182 completed the study, as the procedure failed in 2 participants in the nitroglycerin-treated group and 4 in the placebo group. Baseline demographic and clinical characteristics were similar between 2 groups. Comparing the radial artery diameters before and after the operation, there was a statistically significant increase in the nitroglycerin-treated group (2.48±0.45 versus 2.45±0.46 mm; P=0.003) but a decrease in the placebo control group (2.41±0.50 versus 2.46±0.49 mm; P<0.001). Importantly, the incidence of radial arterial occlusion was substantially lower in the nitroglycerin-treated group than in the placebo control group (5.4% versus 14.4%; P=0.04). There was not significant difference in other complications (forearm hematoma and radial artery pseudoaneurysm, respectively), and there was no incidence of cause hypotension or an intolerable headache. CONCLUSIONS: Subcutaneous injection of nitroglycerin at the radial artery puncture site dilates the radial artery and reduces the incidence of early radial artery occlusion post-catheterization. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn. Unique identifier: ChiCTR-IPR-15006559

Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk

Influence of SNP rs4773144 genotype on gene transcription.

<p>Primary cultures of vascular SMCs (A) and ECs (B) of the A/G genotype for SNP rs4773144 from different individuals were subjected to chromatin immunoprecipitation using an antibody against Pol II, followed by an allelic imbalance analysis of SNP rs4773144, with the use of the TaqMan method to determine the ratio of Ct value of the A allele (detected by a VIC fluorescein-labeled probe) versus the Ct value of the G allele (detected by a FAM fluorescent dye-labeled probe). Upper panels show amplification curves of the A allele (red) and G allele (green). Column charts in the lower panels show the relative fold difference in G to A ratio of Ct values between input DNA and anti-Pol II antibody precipitated chromatin DNA. Columns and error bars represent mean and SEM values.</p

Association between SNP rs4773144 and MI incidence/prevalence in CHD patients.

<p>Association between SNP rs4773144 and MI incidence/prevalence in CHD patients.</p

Influence of SNP rs4773144 genotype on <i>COL4A2</i> and <i>COL4A1</i> expression levels.

<p>Primary cultures of vascular SMCs and ECs from different individuals were genotyped for rs4773144 and subjected to quantitative reverse transcriptase–polymerase chain reaction analysis of <i>COL4A2</i> and <i>COL4A1</i>. Showed in the graphs are relative fold differences in <i>COL4A2</i> (<b>A</b> and <b>B</b>) and <i>COL4A1</i> (<b>C</b> and <b>D</b>) RNA levels in SMCs (<b>A</b> and <b>C</b>) and ECs (<b>B</b> and <b>D</b>), respectively. Columns and error bars represent mean and SEM values; <i>p</i>-values shown are for an additive genetic model.</p

Association of SNP rs4773144 with collagen IV level in atherosclerotic plaques and plaque cap thickness.

<p>Atherosclerotic coronary arteries from different individuals were genotyped for SNP rs4773144 and subjected to histopathological analyses using Image-Pro software. <b>(A)</b> A representative image of immunostaining, blue color indicates COL4A2 staining, and brown smooth muscle alpha-actin. ×400 original magnification. <b>(B)</b> Percentages of COL4A2 immunostain positive areas in atherosclerotic plaques in different genotype groups. <b>(C)</b> Atherosclerotic plaque cap thickness in different genotype groups. <b>(D)</b> Atherosclerotic plaque cap/intima ratios in different genotype groups. Columns and error bars in <b>B</b>-<b>D</b> are mean and SEM values; <i>p</i>-values shown are for an additive genetic model.</p

Influence of SNP rs4773144 genotype on apoptosis.

<p><b>(A)</b> Primary cultures of SMCs from different individuals were genotyped for rs4773144 and subjected to apoptosis assay. Shown in the graph are relative differences in cell apoptotic rate in different genotype groups. Columns and error bars represent mean and SEM values; <i>p</i>-values shown are for an additive genetic model. <b>(B)</b> Primary cultures of ECs of different genotypes for rs4773144 were subjected to immunoblot analysis of the anti-apoptotic protein BCL2. Shown on the left are representative immunoblot images and on the right a graphic presentation of BCL2 band intensities standardized against band intensities of the loading control HSC70. Columns and error bars represent mean and SEM values; <i>p</i>-values shown are for an additive genetic model.</p