The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

Saravi, Babak; Li, Zhen; Lang, Corinna N.; Schmid, Bonaventura; Lang, Frauke K.; Grad, Sibylle; Alini, Mauro; Richards, R. Geoff; Schmal, Hagen; Südkamp, Norbert P.; Lang, Gernot

doi:10.3390/cells10030650

Cited by 43 publications

(58 citation statements)

References 187 publications

(215 reference statements)

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“…The system consists of two regulatory pathways: a pathological pro-inflammatory pathway and a protective anti-inflammatory pathway. AGTR1, involved in the former, can promote vasoconstriction, cell proliferation, inflammation, oxidative stress, hypertrophy, and fibrosis, and angiotensin II–type 1 receptor blockers are widely used to prevent cardiac remodeling after acute myocardial infarction and heart failure ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses

Zheng

Liu

Huang

2021

Front. Cardiovasc. Med.

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Objective: To identify feature immune-related genes (IRGs) in patients with hypertrophic cardiomyopathy (HCM) and verify their ability to diagnose HCM.Methods: The GSE160997 dataset on cardiac tissue from 18 HCM patients and 5 controls was downloaded from the Gene Expression Omnibus database. A false discovery rate <0.05 and |log2 fold change| >1 were the filters applied to identify the differentially expressed genes (DEGs). The differentially expressed IRGs were the intersection results between the DEGs and an IRG dataset from the IMMPORT database. The protein-protein interaction network of differentially expressed IRGs was constructed, and the top 20 hub genes with the most adjacent nodes in the network were selected. The least absolute shrinkage and selection operator regression algorithm and a random forest algorithm were used to identify the feature IRGs as biomarkers that were then verified against GSE36961.Results: A total of 1079 DEGs were identified in GSE160997. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that immune-related mechanisms play an important role in the pathogenesis of HCM. A total of 121 differentially expressed IRGs were identified, and 5 feature IRGs were selected, 4 of which were confirmed as potential biomarkers of HCM by external verification with excellent discrimination ability. A diagnosis model of HCM based on the four feature IRGs was developed and visualized as a nomogram with a C-index of 0.925 (95% confidence interval 0.869–0.981).Conclusion: Our study identified four feature IRGs as biomarkers for the diagnosis of HCM, offering an innovative perspective of the underlying immune-related pathological molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses

Zheng

Liu

Huang

2021

Front. Cardiovasc. Med.

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“…ARBs block the RAS more effectively than ACEIs because approximately 40% of AngII is formed in non-ACE pathways [32]. In addition, while ARBs selectively block the ACE/AngII/AT1R proinflammatory pathway, they can simultaneously activate the AT2R/ACE2/Ang1-7/MasR antiinflammatory pathway [4,33]. Such diverse effects are not demonstrated by ACEIs, which may additionally exert adverse effects by blocking kinin degradation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the presence of tissue RAS (tRAS) was demonstrated. It plays an important role in the pathogenesis of cardiovascular, inflammatory, autoimmune, and neoplastic diseases [4]. RAS inhibitors (RASIs), which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARBs), are widely used in the treatment of arterial hypertension.…”

Section: Introductionmentioning

confidence: 99%

Impact of Renin-Angiotensin System Inhibitors On The Survival of Patients With Rectal Cancer

Zeman

Skałba

Wilk

et al. 2021

Preprint

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Background Renin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection.Methods Between 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan-Meier estimator with the log-rank test and the Cox proportional hazards model.Results The log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p= 0.009) and non-RASI users (p= 0.013). As regards disease-free survival (DFS), worse survival was found in the ACEI group compared to ARB users and it was close to the statistical significance level (p= 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147-0.724, p= 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135-0.850, p= 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016-1.073, p= 0.100), regional lymph node metastasis (ypN+) (HR: 2.157, 95% CI: 1.395-3.334, p= 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799-8.301, p= 0.001). Additional factors affecting DFS included ypN+ (HR: 2.310, 95% CI: 1.374-3.883, p= 0.002) and PNI (HR: 4.351, 95% CI: 1.584-11.954, p= 0.004). Conclusions The use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.

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“…Although the role of tRAS in the evolution of COVID-19 disease is unclear, multiple investigations have reported elevated ACE2 receptor levels in patients, which could be of substantial clinical significance in the future [ 31 ]. A review by Saveri et al proposes that changes in tissue and systemic RAS activity during infection and disease could be attributable to a counterregulatory rise in ACE2 gene expression due to the early ACE2 shedding, so while tissue RAS is the first target, there will be effects on the entire RAS system [ 31 , 32 ].…”

Section: Targeting Covid-19 Therapymentioning

confidence: 99%

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

Khan

Singh

Abrar

et al. 2021

Expert Opinion on Pharmacotherapy

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Introduction The coronavirus disease 2019 (COVID-19) pandemic is the largest public health challenge of the twenty-first century. While COVID-19 primarily affects the respiratory system, manifesting as interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also has implications for the cardiovascular system. Moreover, those admitted to hospital with severe COVID-19 are more likely to have cardiovascular comorbidities such as hypertension and diabetes mellitus. The underlying pathophysiology of why COVID-19 onset can further decline cardiac pathologies as well as trigger acute onset of new cardiac complications is not yet well understood. Areas covered In this review, the authors extensively review literature focused on the current understanding and approaches of managing patients who have underlying cardiovascular diseases and concomitant COVID-19 infection. Furthermore, the authors explore the possible cardiovascular implications of the suggested COVID-19 therapeutic agents that are used to treat this lethal disease. Expert opinion Current evidence is evolving around the many trialed pharmacotherapeutic considerations for the management of coronavirus disease 2019 (COVID-19) in patients with cardiovascular disease. While we await such data, clinicians should advocate for careful consideration of all concomitant medications for those presenting with COVID-19 on a patient-by-patient basis.

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The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

Cited by 43 publications

References 187 publications

Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses

Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses

Impact of Renin-Angiotensin System Inhibitors On The Survival of Patients With Rectal Cancer

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

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