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Background: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis. Methods: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis. Northern blot, rapid amplification of cDNA ends and Sanger sequencing were used to determine its full length. In vitro transcription-translation assay was used to investigate the protein-coding capacity of TPRG1-AS1. RNA fluorescent in situ hybridization was used to confirm its subcellular localization. Loss- and gain-of-function studies were used to investigate the function of TPRG1-AS1. Furthermore, the effect of TPRG1-AS1 on the pathological response was evaluated in carotid balloon injury model, wire injury model, and atherosclerosis model, respectively. Results: TPRG1-AS1 was significantly increased in atherosclerotic plaques. TPRG1-AS1 did not encode any proteins and its full length was 1279nt, which was bona fide a long noncoding RNA. TPRG1-AS1 was mainly localized in cytoplasmic and perinuclear regions in HASMCs. TPRG1-AS1 directly interacted with MYH9 (myosin heavy chain 9) protein in HASMCs, promoted MYH9 protein degradation through the proteasome pathway, hindered F-actin stress fiber formation, and finally inhibited HASMCs migration. Vascular smooth muscle cell-specific transgenic overexpression of TPRG1-AS1 significantly reduced neointima formation, and attenuated atherosclerosis in apolipoprotein E knockout ( Apoe −/− ) mice. Conclusions: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.

Background Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition that affects multiple organs and systems. Case summary A 51-year-old man with a history of occult left apex myocardial infarction diagnosed based on electrocardiographic and echocardiographic findings underwent coronary computed tomography (CT) angiography for the evaluation of coronary artery disease; the findings revealed a soft-tissue mass that surrounded the aortic root and the distal portion of the left coronary artery. The mass was considered an inflammatory lesion; high glucose uptake on positron emission tomography/CT supported this assumption. Coronary angiography revealed 80% stenosis of the distal portion of the left anterior descending artery, which corresponded with the infarction. Intravascular ultrasound revealed hypoechoic regions outside the lumina of the stenotic segment. Based on these findings, IgG4-related periaortitis/periarteritis was suspected; the patient was accordingly treated with oral prednisone and methotrexate. At the 3-month follow-up, the periaortic mass had slightly reduced in size. Discussion Identification and diagnosis of IgG4-related cardiovascular disease are challenging; cases with localized coronary artery involvement may be misdiagnosed as atherosclerotic coronary artery disease. Although imaging techniques, including intracoronary imaging, may aid in differential diagnosis, their sensitivity and specificity still warrant further studies. Practical criteria that facilitate diagnosis and a better understanding of the disease are required.

We compared the diagnostic performance of the ultrasonic flow ratio (UFR) and quantitative flow ratio (QFR) for left main coronary artery (LMCA) stenosis.Evaluation of LMCA stenosis remains challenging because of its complex pathogenesis and severity. Computing QFR allows rapid determination of fractional flow reserve (FFR) from coronary angiograms. A novel intravascular ultrasound (IVUS)-based FFR (UFR) allows rapid FFR computation from IVUS images. Neither of the computational approaches required a pressure wire or hyperemia induction. Previous studies have validated the good diagnostic accuracy of QFR and UFR in identifying hemodynamically significant coronary stenosis using FFR as the reference standard.This retrospective observational study enrolled consecutive patients with intermediate-grade LMCA stenosis who underwent IVUS evaluation. UFR and QFR of all LMCA stenosis patients were assessed, their correlation and agreement were analyzed, and diagnostic performance of UFR in LMCA stenosis was evaluated.Eighty-three paired comparisons between UFR and QFR were obtained. UFR excellently correlated with QFR (r = 0.74, p 0.01). The Bland-Altman plot showed good agreement between UFR and QFR (mean differences: 0.01 ± 0.05, p = 0.34). The area under the curve of UFR for identifying physiological LMCA stenosis was 0.97 (95% confidence interval [CI]: 0.93-1.00, p 0.01). The overall UFR diagnostic accuracy was 0.95 (95% CI: 0.88-0.99).UFR showed excellent correlation and good agreement with QFR in LMCA stenosis assessment, indicating that it is highly feasible to use UFR for functional evaluation of LMCA stenosis.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.

The functional genetic polymorphisms present in the promoters of stromelysin-1 (MMP3) and gelatinase B (MMP9) have been shown to be associated with angiographically measured atherosclerosis; however, haplotype analysis of the genetic polymorphisms occurring in the promoters and coding regions of MMP3 and MMP9 has been infrequently performed in the past. The aim of this study was to analyze the occurrence of the -1612 5A/6A, -376C/G, and Glu45Lys polymorphisms of MMP3 and the -1562C/T and R279Q polymorphisms of MMP9 and their relation to the risk of coronary heart disease (CHD; stenosis >/=50% of the diameter in at least one major coronary artery) in a Chinese Han population. The present study involved 1373 patients with CHD and 695 healthy controls. The Glu45Lys polymorphism of MMP3 was significantly associated with an increased risk of CHD. Compared with the 45Glu homozygotes, 45Lys allele carriers had a significantly elevated risk of CHD (adjusted OR = 1.50; 95%CI 1.11-2.03; p= 0.008). Moreover, haplotype analysis identified both the 6A-C-Lys (-1612 6A, -376C, 45Lys) haplotype and the 6A-G-Lys (-1612 6A,-376G, 45Lys) haplotype of MMP3 as associated with an increased risk of CHD. Our study suggests that common genetic variations in the MMP3 gene may affect the risk of CHD in the Chinese population.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for protein degradation. MMP-2 has been demonstrated to play a pivotal role in myocardial remodeling process that occurs in congestive heart failure (HF). We hypothesized that MMP-2 genetic variations could be associated with systolic HF risk.To test the association of single nucleotide polymorphisms of MMP-2 with systolic HF risk, we performed a hospital-based, case-control study of 605 patients with systolic HF and 689 controls without HF. Three single nucleotide polymorphisms of MMP-2 (rs243864, rs243866, and rs17859821) were genotyped by restriction fragment length polymorphism methods.The genotype frequencies of MMP-2 rs243866 AA and AG in the control group were significantly higher than that in the case group (24.7% versus 17.9%, P0.01). Compared with the GG homozygotes, MMP-2 rs243866 A allele carriers had a significantly lower risk of systolic HF (adjusted OR 0.69, 95% CI 0.49-0.98; P = 0.035). Haplotype analysis indicated the haplotype GGG (rs243864-rs17859821-rs243866) was associated with higher risk of systolic HF (adjusted OR 2.05, 95% CI 1.08-3.89; P = 0.028).The findings of the current study suggest that MMP-2 rs243866 A allele was associated with lower risk of systolic HF in Han Chinese.

MMP-2 is a proteolytic enzyme involved in myocardial remodeling that occurs in congestive heart failure (HF). We hypothesized MMP-2 genetic variations could influence the prognosis of systolic HF.To test our hypothesis, we performed a follow-up study of 605 patients with systolic HF. Three single nucleotide polymorphisms (SNPs) of MMP-2 (rs243864, rs243866, rs17859821) were analyzed by restriction fragment length polymorphism (RFLP) methods.Totally 526 patients (86.9%) were followed up. At follow up (median 24 months), 116 patients (22.1%) died, 102 patients (19.4%) were readmitted because of HF. One, two, three and four year survival rate was 86.9%, 81%, 77.9% and 77.9%. MMP-2 rs17859821 A allele carriers had lower all cause death rate, cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.655, 0.580, 0.705; P = 0.030, 0.008, 0.011). After adjustment for age, bundle branch block, LVEF and NYHA grade by using cox regression analysis, MMP-2 A allele carriers had lower cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.643 and 0.746; P0.05). However, the genotypes had no association with plasma levels of proMMP-2. Haplotype analysis had confirmed the above results. MMP-2 rs243866, rs243864 had no association with systolic HF prognosis.The findings of the present study suggest that MMP-2 rs17859821 A allele was associated with better prognosis of systolic HF in the northern Han Chinese population.