Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients.

A new form of severe acute respiratory syndrome (SARS) caused by SARS-coronavirus 2 (CoV-2), called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (ANG II) is linked to the pathogenesis of COVID-19. This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of ANG II. Furthermore, ANG II has a critical role in the genesis and worsening of hypertension. In this context, the idea that there is a surge in the level of ANG II with COVID-19 infection, causing multiple organ injuries in hypertensive patients becomes attractive. However, the role of other components of the renin angiotensin system (RAS) in this scenario requires elucidation. The identification of other RAS components in COVID-19 hypertension may provide both diagnostic and therapeutic benefits. Here, we summarize the pathophysiologic contributions of different components of RAS in hypertension and their possible correlation with poor outcome observed in hypertensive patients with COVID-19.

Annexin-A1-Derived Peptide Ac2-26 Suppresses Allergic Airway Inflammation and Remodelling in Mice.

Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA1-/- and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA1-/- mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-ß) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma.

Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema.

Our aim was to investigate the role of oxidative stress in elastase-induced pulmonary emphysema. C57BL/6 mice were subjected to pancreatic porcine elastase (PPE) instillation (0.05 or 0.5 U per mouse, i.t.) to induce pulmonary emphysema. Lungs were collected on days 7, 14, and 21 after PPE instillation. The control group was sham injected. Also, mice treated with 1% aminoguanidine (AMG) and inducible NO synthase (iNOS) knockout mice received 0.5 U PPE (i.t.), and lungs were analyzed 21 days after. We performed bronchoalveolar lavage, biochemical analyses of oxidative stress, and lung stereology and morphometry assays. Emphysema was observed histologically at 21 days after 0.5 U PPE treatment; tissues from these mice exhibited increased alveolar linear intercept and air-space volume density in comparison with the control group. TNF-α was elevated at 7 and 14 days after 0.5 U PPE treatment, concomitant with a reduction in the IL-10 levels at the same time points. Myeloperoxidase was elevated in all groups treated with 0.5 U PPE. Oxidative stress was observed during early stages of emphysema, with increased nitrite levels and malondialdehyde and superoxide dismutase activity at 7 days after 0.5 U PPE treatment. Glutathione peroxidase activity was increased in all groups treated with 0.5 U PPE. The emphysema was attenuated when iNOS was inhibited using 1% AMG and in iNOS knockout mice. Furthermore, proteolytic stimulation by PPE enhanced the expression of nitrotyrosine and iNOS, whereas the PPE+AMG group showed low expression of iNOS and nitrotyrosine. PPE stimulus also induced endothelial (e) NOS expression, whereas AMG reduced eNOS. Our results suggest that the oxidative and nitrosative stress pathways are triggered by nitric oxide production via iNOS expression in pulmonary emphysema.