Journal of the Renin-Angiotensin-Aldosterone System最新文献

Objects: To discuss the influence of PM2.5 on myocardial fibrosis and related mechanism.

Methods: PM2.5 particles were prepared into different concentrations of solution to drip into the mice's trachea twice each week. The mice were divided into five groups, Blank control group (C group), NS control group (J group), high dose group (G group, 10 mg/kg), medium dose group (Z group, 5 mg/kg), and 1ow dose group (D group, 2.5 mg/kg). After 6 weeks, the myocardial fibrosis was observed by HE and Masson staining. The expression of Ang II, ERK1/2, and TGF-β₁ was examined by Western Blotting (WB) and Real time PCR (RT-PCR).

Results: The higher dose PM2.5 was administrated, the worse the myocardial fibrosis was in PM2.5 groups. The expression of Ang II, ERK1/2, and TGF-β₁ was increased in higher dose groups in protein and mRNA level.

Conclusion: 1. PM2.5 induced the cardiac fibrosis. 2. PM2.5 dripped into trachea in mice model activated the expression of Ang II, ERK1/2, and TGF-β₁. The activation of renin-angiotensin system (RAS) was suggested to participate in the cardiac fibrosis induced by PM2.5.

Introduction: The roles of angiotensin II (Ang II) in the brain are still under investigation. In this study, we investigated if Ang II influences differentiation of human neuroblastoma cells with simultaneous activation of NADPH oxidase and reactive oxygen species (ROS). Moreover, we investigated the Ang II receptor type involved during differentiation.

Methods: Human neuroblastoma cells (SH-SY5Y; 5 × 10⁵ cells) were exposed to Ang II (600 nM) for 24 h. Differentiation was monitored by measuring MAP2 and NF-H levels. Cell size and ROS were analyzed by flow cytometry, and NADPH oxidase activation was assayed using apocynin (500 μM). Ang II receptors (ATR) activation was assayed using ATR blockers or Ang II metabolism inhibitors (10^-7 M).

Results: (1) Cell size decreased significantly in Ang II-treated cells; (2) MAP2 and ROS increased significantly in Ang II-treated cells with no changes in viability; (3) MAP2 and ROS decreased significantly in cells incubated with Ang II plus apocynin. (4) A significant decrease in MAP2 was observed in cells exposed to Ang II plus PD123.319 (AT2R blocker).

Conclusion: Our findings suggest that Ang II influences differentiation of SH-SY5Y by increasing MAP2 through the AT2R. The increase in MAP2 and ROS were also mediated through NADPH oxidase with no cell death.

Objective: Mechanical ventilation is an important treatment for critically ill patients. Physicians generally perform a spontaneous breathing trial (SBT) to determine whether the patients can be weaned from mechanical ventilation, but almost 17% of the patients who pass the SBT still require respiratory support. Cardiac dysfunction is an important cause of weaning failure. The use of brain natriuretic peptide or N-terminal pro-BNP is a simple method to assess cardiac function. We performed a systematic review of investigations of brain natriuretic peptide or N-terminal pro-BNP as predictors of weaning from mechanical ventilation.

Data sources: PubMed (1950 to December 2020), Cochrane, and Embase (1974 to December 2020), and some Chinese databases for additional articles (China Biology Medicine (CBM), China Science and Technology Journal Database (CSTJ), and Wanfang Data and China National Knowledge Infrastructure (CNKI)).

Study selection: We systematically searched observation studies investigating the predictive value of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide in weaning outcome of patients with mechanical ventilation.

Data extraction: Two independent reviewers extracted data. The differences are resolved through consultation.

Data synthesis: We included 18 articles with 1416 patients and extracted six index tests with pooled sensitivity and specificity for each index test. For the BNP change rate predicting weaning success, the pooled sensitivity was 89% (83%-94%) and the pooled specificity was 82% (72%-89%) with the highest pooled AUC of 0.9511.

Conclusions: The brain natriuretic peptide change rate is a reliable predictor of weaning outcome from mechanical ventilation.

Background: The current meta-analytic study explored the relation between ACE gene insertion/deletion (I/D), and the risk of EH by reviewing relevant trials so as to determine the association between Angiotensin Converting Enzyme (ACE) gene polymorphism and essential hypertension (EH) susceptibility.

Methods: Relevant studies published before May 2019 were collected from the PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases.

Results: Fifty-seven studies involving a total of 32,862 patients were included. These studies found that ACE gene D allele was associated with higher EH susceptibility in allelic model, homozygote model, dominant model, and regressive model, and that Asian population with ACE gene D allele showed a higher EH susceptibility in all these models. Moreover, ACE gene D allele was found closely related to a higher EH susceptibility in the subgroups of HWE, NO HWE, Caucasian population, and Mixed population, with the majority being males in allelic model, homozygote model, and regressive model and the majority being females in allelic model.

Conclusion: ACE gene D allele is associated with an overall higher EH susceptibility, which is confirmed in the subgroup analysis of Asian population, HWE, NO HWE, Caucasian population, and Mixed population.

End-stage heart failure is a condition in which the up-regulation of the systemic and local renin-angiotensin-aldosterone system (RAAS) leads to end-organ damage and is largely irreversible despite optimal medication. Left ventricular assist devices (LVADs) can downregulate RAAS activation by unloading the left ventricle and increasing the cardiac output translating into a better end-organ perfusion improving survival. However, the absence of pulsatility brought about by continuous-flow devices may variably trigger RAAS activation depending on left ventricular (LV) intrinsic contractility, the design and speed of the pump device. Moreover, the concept of myocardial recovery is being tested in clinical trials and in this setting LVAD support combined with intense RAAS inhibition can promote recovery and ensure maintenance of LV function after explantation. Blood pressure control on LVAD recipients is key to avoiding complications as gastrointestinal bleeding, pump thrombosis and stroke. Furthermore, emerging data highlight the role of RAAS antagonists as prevention of arteriovenous malformations that lead to gastrointestinal bleeds. Future studies should focus on the role of angiotensin receptor inhibitors in preventing myocardial fibrosis in patients with LVADs and examine in greater details the target blood pressure for these patients.

Hypothesis: A lack of contraction of cerebral microarterioles to Ang II ("resilience") depends on cyclooxygenase (COX) and lipocalin type prostaglandin D sythase L-PGDS producing PGD₂ that activates prostaglandin D type 1 receptors (DP1Rs) and nitric oxide synthase (NOS).

Materials & methods: Contractions were assessed in isolated, perfused vessels and NO by fluorescence microscopy.

Results: The mRNAs of penetrating intraparenchymal cerebral microarterioles versus renal afferent arterioles were >3000-fold greater for L-PGDS and DP1R and 5-fold for NOS III and COX 2. Larger cerebral arteries contracted with Ang II. However, cerebral microarterioles were entirely unresponsive but contracted with endothelin 1 and perfusion pressure. Ang II contractions were evoked in cerebral microarterioles from COX1 -/- mice or after blockade of COX2, L-PGDS or NOS and in deendothelialized vessels but effects of deendothelialization were lost during COX blockade. NO generation with Ang II depended on COX and also was increased by DP1R activation.

Conclusion: The resilience of cerebral arterioles to Ang II contractions is specific for intraparenchymal microarterioles and depends on endothelial COX1 and two products that are metabolized by L-PGDS to generate PGD₂ that signals via DP1Rs and NO.

Background: The clinical use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in patients with COVID-19 infection remains controversial. Therefore, we performed a meta-analysis on the effects of ACEI/ARB on disease symptoms and laboratory tests in hypertensive patients infected with COVID-19 virus and those who did not use ACEI/ARB.

Methods: We systematically searched the relevant literatures from Pubmed, Embase, EuropePMC, CNKI, and other databases during the study period of 31 December 2019 (solstice, 15 March 2020), and analyzed the differences in symptoms and laboratory tests between patients with COVID-19 and hypertension who used ACEI/ARB drugs and those who did not. All statistical analyses were performed with REVMAN5.3.

Results: We included a total of 1808 patients with hypertension diagnosed with COVID-19 in six studies. Analysis results show that ACEI/ARB drugs group D-dimer is lower (SMD = -0.22, 95%CI: -0.36 to -0.06), and the chances of getting fever is lower (OR = 0.74, 95%CI: 0.55 to 0.98). Meanwhile, laboratory data and symptoms were not statistical difference, but creatinine tends to rise (SMD = 0.22, 95% CI: 0.04 to 0.41).

Conclusion: We found that the administration of ACEI/ARB drugs had positive effect on reducing D-dimer and the number of people with fever. Meanwhile it had no significant effect on other laboratory tests (creatinine excepted) or symptoms in patients with COVID-19, while special attention was still needed in patients with renal insufficiency.