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BackgroundDevelopment of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.ResultsIn this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.ConclusionsOur results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems.

What is known and objective: Lorcaserin is a selective serotonin 2c receptor agonist approved as an anti‐obesity agent. The additional cardiometabolic benefits associated with lorcaserin have not been conclusively established. The aim of the systematic review and meta‐analysis is to examine the effects of lorcaserin on blood pressure, heart rate and other metabolic parameters in overweight and obese patients from randomized controlled clinical trials (RCTs). Methods: A literature search was conducted on PubMed, EMBASE and Cochrane Central using the search terms 'lorcaserin' and 'randomized controlled trials' without language restrictions. RCTs with a follow‐up period of at least 24 weeks were included in the meta‐analysis. Results and discussion: Six studies with 9452 patients in the lorcaserin group and 9392 patients in the placebo group were included. Compared with placebo, lorcaserin not only reduced weight, BMI and waist circumference but also improved SBP, DBP, heart rate, LDL, triglycerides, fasting plasma glucose and HbA1c. Our findings suggest that lorcaserin has trivial though consistent and favourable effects on blood pressure, heart rate and metabolic syndrome. What is new and conclusion: Lorcaserin improved all cardiometabolic parameters modestly in addition to its weight loss effect in overweight and obese patients. More research is needed to determine its long‐term cardiovascular benefits. [ABSTRACT FROM AUTHOR]

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Catheter-based renal denervation (RDN) has emerged as a promising treatment option for hypertension. However, randomized controlled trials (RCTs) have reported conflicting results on blood pressure (BP) reduction. Patient- and procedure-related confounders have been implied as the potential sources of inconsistent BP responses. We aimed to investigated whether unplanned and frequent medication changes in RDN studies affected the BP response to RDN by conducting sensitivity and subgroup analyses, according to antihypertensive medication change rates in a meta-analysis of RCTs., Methods: We searched the PUBMED, EMBASE, and COCHRANE databases up to May 2018. RCTs that studied the effects of RDN on hypertensive patients were included. A meta-analysis was carried out using RevMan 5.3., Results: A total of 12 studies were included, of which four fulfilled the inclusion criteria of < 10% medication change rate in our review. Subgroup meta-analyses of the four RCTs with < 10% medication change rates showed statistically significant reductions of 6.07 mmHg and 7.12 mmHg in 24-hour and office systolic BP, respectively. The 24-hour and office diastolic BP were also reduced (mean difference = -3.89 mmHg and -4.27 mmHg, respectively). These subgroup analyses had no heterogeneity (I 2 = 0%). In contrast, the pooled analysis of the 12 studies and the subgroup analysis of eight studies with > 10% medication change rates both had a high level of heterogeneity and no significant BP reduction., Conclusions: The effectiveness of RDN was demonstrated across a broad range of antihypertensive medications used at baseline after removing the confounder of unplanned medication changes.