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

Thrombocytes (platelets) are the type of blood cells that are involved in hemostasis, thrombosis, etc. For the conversion of megakaryocytes into thrombocytes, the thrombopoietin (TPO) protein is essential which is encoded by the TPO gene. TPO gene is present in the long arm of chromosome number 3 (3q26). This TPO protein interacts with the c-Mpl receptor, which is present on the outer surface of megakaryocytes. As a result, megakaryocyte breaks into the production of functional thrombocytes. Some of the evidence shows that the megakaryocytes, the precursor of thrombocytes, are seen in the lung's interstitium. This review focuses on the involvement of the lungs in the production of thrombocytes and their mechanism. A lot of findings show that viral diseases, which affect the lungs, cause thrombocytopenia in human beings. One of the notable viral diseases is COVID-19 or severe acute respiratory syndrome caused by SARS-associated coronavirus 2 (SARS-CoV-2). SARS-CoV-2 caused a worldwide alarm in 2019 and a lot of people suffered because of this disease. It mainly targets the lung cells for its replication. To enter the cells, these virus targets the angiotensin-converting enzyme-2 (ACE-2) receptors that are abundantly seen on the surface of the lung cells. Recent reports of COVID-19-affected patients reveal the important fact that these peoples develop thrombocytopenia as a post-COVID condition. This review elaborates on the biogenesis of platelets in the lungs and the alterations of thrombocytes during the COVID-19 infection.

Objective: Essential hypertension (EH) is a common cardiovascular disease that endangers human health. Its pathogenesis is complex and has not been fully elucidated. We explore the association between EH and interactions among polymorphisms of the angiotensin converting enzyme (ACE) gene in the Hefei region, Anhui, China.

Methods: A total of 500 participants (400 hypertensive and 100 normotensive) were included in this study. The polymorphisms were detected via improved multiple ligase detection reaction (iMLDR). To improve the accuracy of prediction, multifactor dimensionality reduction (MDR) was used to analyze the overall effect of interactions among seven loci on the incidence of EH.

Results: The frequencies of polymorphisms in the ACE genes rs12709426, rs4291, rs4309, rs4331, rs4343, rs4459609, and rs4461142 in the EH group were not statistically significantly different from those in the control group. We also found that the single nucleotide polymorphism (SNP) rs12709426 only had a homozygous AA genotype and no polymorphisms. There were no differences in the frequency of genetic polymorphisms between the EH and control groups. The best model explaining the EH group was the combined effect of ACE genes rs4291, rs4309, and rs4461142.

Conclusion: There is an interaction effect among ACE gene loci in EH patients in Hefei region, Anhui, China. Also, the ACE gene SNP rs12709426 only has a homozygous AA genotype and does not show an association with EH.

Background: Essential hypertension is the result of modifiable and genetic factors, and it is associated with increased risk for atherothrombosis. Some polymorphisms are associated with hypertensive disease. The objective was to analyze the association between eNOS Glu298Asp, MTHR C677T, AGT M235T, AGT T174M, and A1166C and ACE I/D polymorphisms with essential hypertension in the Mexican population.

Materials and methods: In the present study, 224 patients with essential hypertension and 208 subjects without hypertension were included. The Glu298Asp, C677T, M235T, T174M, A1166C, and I/D polymorphisms were determined by the PCR-RFLP technique.

Results: We found statistical differences in age, gender, BMI, systolic and diastolic blood pressure, and total cholesterol between control and cases. However, we found no significant differences in HbA1c and triglycerides between both groups. We observed statistical significant differences in the genotype distribution of Glu298Asp (P = 0.001), I/D (P = 0.02), and M235T (P = 0.004) polymorphisms between both groups. In contrast, there were no differences related to distribution of genotypes of MTHFR C677T (P = 0.12), M174T (P = 0.46), and A1166C (P = 0.85) between cases and control groups.

Conclusions: We identified that Glu298Asp, I/D, and M234T polymorphisms represented an increased risk for essential hypertension and those genetic variants could contribute to the presence of endothelial dysfunction and vasopressor effect, hyperplasia, and hypertrophy of smooth muscle cells, which had an impact for hypertension. In contrast, we found no association between C677C, M174T, and A1166C polymorphisms and hypertensive disease. We suggested that those genetic variants could be identified in individuals with high risk to avoid hypertension and thrombotic disease.

Objective: We reported that rats infused with angiotensin II (Ang II) are not only a model of hypertension but also of augmented 24 h blood pressure variability (BPV). In this study, we examined the mechanisms for Ang II-induced BPV, focusing on BP, heart rate (HR), baroreceptor reflex sensitivity (BRS), and medial area of the aortic arch.

Methods: Nine-week-old male Wistar rats were infused with subcutaneous 5.2 μg/kg/h Ang II with or without oral administration with 30 mg/kg/day azelnidipine for 14 days. BP and HR were recorded every 15 min under an unrestrained condition by a radiotelemetry system, while BPV was evaluated by standard deviation of BP. BRS was quantified by a sequence analysis, and medial thickness of the aortic arch was measured by microscopic examination.

Results: BPV increased at days 7 and 14 following continuous infusion of Ang II. Before the infusion, a positive correlation was found between BP and HR, but it became negative at day 7 and then weakened or disappeared at day 14. BRS was slightly impaired at day 7 and significantly lowered at day 14, a phenomenon accompanied by thickened medial area of the aortic arch in Ang II-infused rats. Those Ang II-induced alterations were all significantly attenuated by azelnidipine.

Conclusions: The present findings suggest sequential changes in the mechanisms behind augmented BPV in rats continuously infused with Ang II over 14 days.

Introduction: There has been controversy about renin-angiotensin system (RAS) inhibition in IgAN patients with advanced (stage 4) chronic kidney disease (CKD). Therefore, we investigated the effect of RAS blockade in these patients.

Methods: Renal specimens of 50 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2020, were stained using immunohistochemistry to detect the expression of RAS receptors (AT1R, AT2R, MasR, and MrgD). The primary endpoint was a composite of end-stage renal disease (ESRD) and death. Main baseline information and the administration of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were collected.

Results: During a median follow-up time of 25.5 months, 21 (42.0%) patients reached ESRD and none died. Six patients had a baseline eGFR of 15-20 ml/min/1.73m², and reached ESRD with a median renal survival time of 7.0 (range 6.0-23.0) months. Among patients with a baseline eGFR of 20-30 ml/min/1.73m², the percentage of patients using ACEI/ARB in progressive group was much lower than that in stable group (33.3% vs. 62.1%, P = 0.045), together with a shorter renal survival time in progressive group (26.0 vs. 30.5 months, P = 0.033). Macroproteinuria (24 h - UP ≥ 2.5 g) was also associated with a shorter renal survival time, as well as a significant decline in eGFR of stable group (24.4 vs. 26.4 ml/min/1.73 m², P = 0.026). Lower eGFR [hazards ratio (HR), 0.829, 95% confidence interval (CI), 0.724-0.950; P = 0.007] and use of ACEI/ARB (HR, 0.356, 95% CI, 0.133-0.953; P = 0.040) were predictive of time to ESRD in this stage. No differences were found in the expression of AT1R, AT2R, MasR, and MrgD of renal tissues at the time of biopsy between stable and progressive groups.

Conclusion: Contingent on monitoring serum creatinine and potassium levels, IgAN with macroproteinuria and a GFR of 20-30 ml/min/1.73m² may still benefits from intrarenal RAS inhibition.