Vascular injury, remodeling, as well as angiogenesis, are the leading causes of coronary or cerebrovascular disease. The blood vessel functional imbalance trends to induce atherosclerosis, hypertension, and pulmonary arterial hypertension. As several genes have been identified to be dynamically regulated during vascular injury and remodeling, it is becoming widely accepted that several types of non-coding RNA, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are involved in regulating the endothelial cell and vascular smooth muscle cell (VSMC) behaviors. Here, we review the progress of the extant studies on mechanistic, clinical and diagnostic implications of miRNAs and lncRNAs in vascular injury and remodeling, as well as angiogenesis, emphasizing the important roles of miRNAs and lncRNAs in vascular diseases. Furthermore, we introduce the interaction between miRNAs and lncRNAs, and highlight the mechanism through which lncRNAs are regulating the miRNA function. We envisage that continuous in-depth research of non-coding RNAs in vascular disease will have significant implications for the treatment of coronary or cerebrovascular diseases. Vascular network is an intricate series of vessels that act as conduits for blood flow. Their injury and remodeling contribute to atherosclerosis, restenosis after angioplasty, hypertension, and other diseases. Molecular mechanisms that underlie vascular injury and remodeling have been intensively studied during the last two decades [13]. As reported, a number of genes have been shown to regulate vascular remodeling and angiogenesis [47]. As it is increasingly acknowledged that several types of non-coding RNAs are also involved in these processes, they have become a new focus of scientific research [8].According to the recent discoveries in the field of RNA, nearly 60% of transcripts seem to lack protein-coding capacity, termed non-coding RNAs [9]. Bioinformatics observations suggest that non-coding RNAs tend to exist in greater numbers in more sophisticated organisms [10]. Functional studies reveal that non-coding RNAs have essential functions in regulating epigenetic processes, and emerge as important regulators of life activities [11]. Among non-coding RNAs, miRNAs and lncRNAs are particularly interesting and are thus intensively investigated. Here, we provide an overview of the extant research findings pertaining to miRNAs and lncRNAs in vascular functional maintenance, injury, remodeling, and angiogenesis. Moreover, we highlight their implications for the treatment of atherosclerosis, hypertension and other vascular-related disease.

Background: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. Methods: In total 1,216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography (CCTA) were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary endpoint was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary endpoints included major adverse cardiovascular events (MACE), quality of life, symptoms of angina, and medical expenditure at 1 year. Results: Baseline characteristics were similar in both groups with 72.4% (881/1,216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared to standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] vs. 46.2% [223/483] P<0.001). Overall more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] vs. 42.8% [260/608], P=0.02), but of MACE at 1 year did not differ (hazard ratio, 0.88; 95%CI, 0.59 to 1.30). Quality of life and symptoms improved similarly during follow-up in both groups and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233; 95%CI, -¥8165 to ¥973, P=0.07). Conclusions: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events.

Background: The diagnostic accuracy of CT-derived fractional flow reserve (CT-FFR) in clinical application has been well validated. This advanced technology focus on evaluating anatomical stenosis and functional ischemia simultaneously. However, the effect of CT-FFR on the management of decision making has not been fully evaluated in randomized controlled design. Method/design: TARGET study is a pragmatic, multicenter, prospective, open-label, and randomized controlled trial evaluating the effect of a CCTA/CT-FFR strategy (group A) versus usual care (group B) on intermediate-to-high risk patients with suspected CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 1216 subjects will be enrolled and followed up for 12 months. This study will be performed in 6 Chinese hospitals, and the primary endpoint is the planned ICA without significant obstructive CAD within 90 days. The secondary endpoints include MACE, quality of life, medical expenditure, and cumulative radiation exposure during 1-year follow-up. Discussion: The study will provide information to patients, health care providers, and other stakeholders in China about which strategy could be more effective in the management of intermediate-to-high risk patients with suspect CAD. Trial registration: ClinicalTrials.gov NCT03901326. Registered on 3 April 2019.

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Objective. To explore the association between EAT volume and plaque precise composition and high risk plaque detected by coronary computed tomography angiography (CCTA). Methods. 101 patients with suspected coronary artery disease (CAD) underwent CCTA examination from March to July 2019 were enrolled, including 70 cases acute coronary syndrome (ACS) and 31 cases stable angina pectoris (SAP). Based on CCTA image, atherosclerotic plaque precise compositions were analyzed using dedicated quantitative software. High risk plaque was defined as plaque with more than 2 high risk features (spotty calcium, positive remolding, low attenuation plaque, napkin-ring sign) on CCTA image. The association between EAT volume and plaque composition was assessed as well as the different of correlation between ACS and SAP was analyzed. Multivariable logistic regression analysis was used to explore whether EAT volume was independent risk factors of high risk plaque (HRP). Results. EAT volume in the ACS group was significantly higher than that of the SAP group ( 143.7 ± 49.8  cm3 vs. 123.3 ± 39.2  cm3, P = 0.046 ). EAT volume demonstrated a significant positive correlation with total plaque burden ( r = 0.298 , P = 0.003 ), noncalcified plaque burden ( r = 0.245 , P = 0.013 ), lipid plaque burden ( r = 0.250 , P = 0.012 ), and homocysteine ( r = 0.413 , P ≤ 0.001 ). In ACS, EAT volume was positively correlated with total plaque burden ( r = 0.309 , P = 0.009 ), noncalcified plaque burden ( r = 0.242 , P = 0.044 ), and lipid plaque burden ( r = 0.240 , P = 0.045 ); however, no correlation was observed in SAP. Patients with HRP have larger EAT volume than those without HRP ( 169 ± 6.2  cm3 vs. 130.6 ± 5.3  cm3, P = 0.002 ). After adjustment by traditional risk factors and coronary artery calcium score (CACS), EAT volume was an independent risk predictor of presence of HRP (OR: 1.018 (95% CI: 1.006-1.030), P = 0.004 ). Conclusions. With the increasing EAT volume, more dangerous plaque composition burdens increase significantly. EAT volume is a risk predictor of HRP independent of convention cardiovascular risk factors and CACS, which supports the potential impact of EAT on progression of coronary atherosclerotic plaque.

Objective: To evaluate the diagnostic performance of automated quantitative analysis by coronary computed tomography angiography (CCTA) in identifying lesion-specific hemodynamic abnormality. Methods: A total of 132 patients (mean age, 61 y; 86 men) with 169 vessels (with 30% to 90% diameter stenosis), who successively underwent invasive coronary angiography with evaluation of fractional flow reserve (values ≤0.8 were defined as lesion-specific hemodynamic abnormalities), were analyzed by CCTA. CCTA images were quantitatively analyzed using automated software to obtain the following index: maximum diameter stenosis (MDS%); maximum area stenosis (MAS%); lesion length (LL); volume and burden (plaque volume×100 per vessel volume) of total plaque (total plaque volume [TPV], total plaque burden [TPB]), calcified plaque (calcified plaque volume [CPV], calcified plaque volume burden [CPB]), noncalcified plaque (noncalcified plaque volume [NCPV], noncalcified plaque volume burden [NCPB]), lipid plaque (lipid plaque volume [LPV], lipid plaque burden [LPB]), and fibrous plaque (fibrotic plaque volume [FPV], fibrotic plaque burden [FPB]); napkin-ring sign (NRS); remodeling index (RI); and eccentric index (EI). Logistic regression and area under the receiver operating characteristics (AUC) were used for statistical analysis. Results: Fractional flow reserve ≤0.80 was found in 57 (33.73%) of the 169 vessels. Vessels with hemodynamic significance had greater MDS% (64.43%±8.69% vs. 57.33%±9.95%, P<0.001), MAS% (73.18%±8.56% vs. 64.66%±8.95%, P<0.001), and lipid plaque burden (12.75% [9.73%, 19.56%] vs. 9.41% [4.10%, 15.70%], P=0.01) compared with vessels with normal hemodynamics. In multivariable logistic regression analysis, MAS% >68% (odds ratio: 7.20, 95% confidence interval [CI]=2.89-17.91, P<0.001) and LPB >10.03% (odds ratio=4.32, 95% CI=1.36-13.66, P=0.01) were significant predictors of hemodynamic abnormalities. In predicting lesion-specific hemodynamic abnormalities, the AUC was 0.77 (95% CI=0.70-0.85) for MAS% versus 0.71 (95% CI=0.63-0.79) for MDS% (P<0.05), 0.66 (95% CI=0.58-0.74) for LPV (P<0.05), 0.66 (95% CI=0.58-0.74) for LPB (P<0.05), and 0.63 (95% CI=0.54-0.71) for TPB (P<0.05). The AUC of MAS%+LPB (0.83, 95% CI=0.76-0.89) was significantly improved compared with that of MAS% (0.77, 95% CI=0.70-0.85, P<0.05). Conclusions: Compared with MDS% and the volume burdens of plaque compositions, MAS% has a higher diagnostic accuracy for coronary hemodynamic abnormalities in the precise quantitative analysis of coronary plaques on the basis of CT. Furthermore, MAS%+LPB might improve the diagnostic accuracy beyond MAS% alone.

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Background: The diagnostic accuracy of CT-derived fractional flow reserve (CT-FFR) in clinical application has been well validated. This advanced technology focus on evaluating anatomical stenosis and functional ischemia simultaneously. However, the effect of CT-FFR on the management of decision making has not been fully evaluated in randomized controlled design. Method/design: TARGET study is a pragmatic, multicentre, prospective, open-label and randomized controlled trial evaluating the effect of a CCTA/CT-FFR strategy (Group A) versus usual care (Group B) on intermediate-to-high risk patients with suspected CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 1216 subjects will be enrolled and followed up for 12 months. This study will be performed in 6 Chinese hospitals, and the primary endpoint is the planned ICA without significant obstructive CAD within 90 days. The secondary endpoints include MACE, quality of life, medical expenditure, and cumulative radiation exposure during 1-year follow-up.Disscusion: The study will provide information to patients, health care providers and other stakeholders in China about which strategy could be more effective in the management of intermediate-to-high risk patients with suspect CAD.Trial registration:ClinicalTrials.gov, NCT03901326, Registered on 03 April 2019.