The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes, among which inflammation and blood pressure regulation. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, and therefore a lot of research has been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical investigations and experimental analyzes quantifying, e.g., the levels and activity of RAS components. We performed a comprehensive meta-analysis of these data in view of disentangling the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. We also review the effects of several RAS-targeting drugs and how they could potentially help restore the normal RAS functionality and minimize the COVID-19 severity. Finally, we discuss the conflicting evidence found in the literature and the open questions on RAS dysregulation in SARS-CoV-2 infection whose resolution would improve our understanding of COVID-19.
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http://dx.doi.org/10.3390/cells10102755 | DOI Listing |
Front Nephrol
December 2024
Renal Pathophysiology Laboratory, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
In glomerulopathies, endothelial dysfunction and the presence of histological vascular lesions such as thrombotic microangiopathy, arteriolar hyalinosis, and arteriosclerosis are related to a severe clinical course and worse renal prognosis. The endothelial cell, which naturally has anti-inflammatory and anti-thrombotic regulatory mechanisms, is particularly susceptible to damage caused by various etiologies and can become dysfunctional due to direct/indirect injury or a deficiency of protective factors. In addition, endothelial regulation and protection involve participation of the complement system, factors related to angiogenesis, the renin-angiotensin system (RAS), endothelin, the glycocalyx, the coagulation cascade, interaction between these pathways, interactions between glomerular structures (the endothelium, mesangium, podocyte, and basement membrane) and interstitial structures (tubules, arterioles and small vessels).
View Article and Find Full Text PDFAnticancer Agents Med Chem
January 2025
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
Long non-coding RNA (lncRNA) is a type of non-coding RNA distinguished by a length exceeding 200 nucleotides. Recent studies indicated that lncRNAs participate in various biological processes, such as chromatin remodeling, transcriptional and post-transcriptional regulation, and the modulation of cell proliferation, death, and differentiation, hence influencing gene expression and cellular function. ADAMTS9-AS1, an antisense long non-coding RNA situated on human chromosome 3p14.
View Article and Find Full Text PDFRasopathies, including Noonan Syndrome (NS) and Neurofibromatosis type 1 (NF1), are developmental disorders caused by germline mutations in genes of the RAS/mitogen-activated protein kinase pathway (RAS-MAPK). This study investigates irritability, a highly prevalent transdiagnostic construct, in children with Rasopathies and the impact of Rasopathy status on the associations between irritability, emotional dysregulation-related disorders, and social skills impairments. The sample comprise 174 children aged 4-17 (age mean = 9.
View Article and Find Full Text PDFNeurosci Biobehav Rev
January 2025
Department of Pharmaceutical Sciences, Faculty of Life Sciences, Gurugram University (A State Govt. University), Gurugram, Haryana, India. Electronic address:
Plexins are a family of transmembrane receptors known for their diverse roles in neural development, axon guidance, neuronal migration, synaptogenesis, and circuit formation. Semaphorins are a class of secreted and membrane proteins that act as primary ligands for plexin receptors. Semaphorins play a crucial role in central nervous system (CNS) development by regulating processes such as axonal growth, neuronal positioning, and synaptic connectivity.
View Article and Find Full Text PDFPediatr Allergy Immunol Pulmonol
January 2025
Clinical Immunology Unit, Faculty of Medicine and Health Sciences, Department of Paediatrics, Universiti Putra Malaysia, Selangor, Malaysia.
: RAS guanyl-releasing protein 1 (RASGRP1) deficiency is characterized by immune dysregulation and Epstein-Barr virus (EBV)-related lymphoproliferation. Diffuse mesangial sclerosis is one of the infrequent causes of infantile nephrotic syndrome. : Here, we described a 7-year-old girl who was diagnosed with diffuse mesangial sclerosis at 5 months old and subsequently developed chronic bilateral neck swelling at the age of 3 years.
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