Immunomodulatory properties of captopril, an ACE inhibitor, on LPS-induced lung inflammation and fibrosis as well as oxidative stress

Boskabadi, Javad; Askari, Vahid Reza; Hosseini, Mahmoud; Boskabady, Mohammad Hossein

doi:10.1007/s10787-018-0535-4

Cited by 42 publications

(31 citation statements)

References 50 publications

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“…61 In contrast, the increase in vascular permeability and leakage was significantly attenuated in the lungs of knockout mice for AT 1 R (Ata1a). 61 Taken together with experimental studies showing beneficial effects of ACEIs 63,64 or ARBs, 65,66 or ACE2 supplementation, these data indicate that loss of ACE2 expression and increased Ang II-AT 1 R axis activation promote the disease in lung injury models. 55,60,67 Due to its terminal carboxypeptidase activity, ACE2 is also involved in the modification of other bioactive peptides 68 including the active metabolite of bradykinin, i.e.…”

Section: Inflammatory Dysregulation In Hypertension As a Possible Patmentioning

confidence: 74%

Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19

Kreutz

Algharably

Azizi

et al. 2020

Cardiovascular Research

325

335

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Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin–angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.

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Section: Inflammatory Dysregulation In Hypertension As a Possible Patmentioning

confidence: 74%

Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19

Kreutz

Algharably

Azizi

et al. 2020

Cardiovascular Research

325

335

View full text Add to dashboard Cite

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“…The latter study also showed that the ratio of ACE1/ACE2 expression is increased in injury and that captopril attenuated injury and decreased that ratio. These findings were replicated in a study in which captopril reduced inflammatory cytokines and monocyte infiltration in bronchoalveolar fluid (Boskabadi, Askari, Hosseini, & Boskabady, 2019). In addition, in a murine H5N1 influenza infection model, treatment with losartan improved survival and reduced oedema, lung injury and immune cell infiltration (Yan et al, 2015).…”

Section: A Model For How Imbalance In the Ras Pathway Produces Covid‐mentioning

confidence: 68%

“…Ang II also has pro-fibrotic effects on fibroblasts that reside in interstitial spaces around alveoli (e.g. Uhal, Kyong Kim, Li, & Molina-Molina, 2007; and increases apoptosis of endothelial cells and endothelial permeability in the surrounding capillary network (Bodor et al, 2012;Watanabe, Barker, & Berk, 2005), which can increase fluid entry and immune infiltration into regions of the lung. Ang II also affects various types of immune cells (Forrester et al, 2018), increasing macrophage infiltration, ROS production and release of pro-inflammatory cytokines.…”

Section: A Model For How Imbalance In the Ras Pathway Produces Covimentioning

confidence: 99%

A hypothesis for pathobiology and treatment of COVID‐19: The centrality of ACE1/ACE2 imbalance

Sriram

Insel

2020

British J Pharmacology

178

200

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Angiotensin Converting Enzyme2 is the cell surface binding site for the coronavirus SARS-CoV-2, which causes COVID-19. We propose that an imbalance in the action of ACE1-and ACE2-derived peptides, thereby enhancing angiotensin II (Ang II) signalling is primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of Ang II to Ang peptides that counteract pathophysiological effects of ACE1-generated ANG II. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: (a) AT receptor antagonists; (b) ACE1 inhibitors (ACEIs); (iii) agonists of receptors activated by ACE2-derived peptides (e.g. Ang (1-7), which activates MAS1); (d) recombinant human ACE2 or ACE2 peptides as decoys for the virus.Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved AT antagonists and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.

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“…In animal studies, the administration of enalapril in mice with acute lung injury quickly reduced Ang II levels [ 58 ], while the administration of captopril reduced IFN-γ, prostaglandin E2 (PGE2), and TGF-β1 levels and increased interleukin 4 (IL-4) levels, thereby regulating the Th1/Th2 balance [ 59 ] and reducing pulmonary inflammation and lung injury. A retrospective study showed that continuous in-hospital administration of ACE inhibitors can reduce mortality and intubation rates in non-SARS patients [ 60 ].…”

Section: Treatment Of Cardiovascular Injury Associated With Sars-cov-mentioning

confidence: 99%

Mechanisms and treatments of myocardial injury in patients with corona virus disease 2019

Peng

Tan

et al. 2020

Life Sciences

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The infection epidemic event of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was formally declared a pandemic by World Health Organization on March 11th, 2020. Corona Virus Disease 2019 (COVID-19) is caused by SARS-CoV-2, a new type of coronavirus, which has high contagion and mainly causes respiratory symptoms. With the increase in confirmed cases, however, the infection symptoms turn to be diverse with secondary or first clinical symptoms relating to damage of the cardiovascular system and changes of myocardial enzyme spectrum, cardiac troponin I, electrocardiogram, cardiac function. The occurrence of extra-pulmonary manifestations, including immediately and long-term damage, means that the overall health burden caused by SARS-CoV-2 infection may be under-estimated because COVID-19 patients developed cardiovascular system injury are more likely to become serious. The factors such as directly pathogen-mediated damage to cardiomyocytes, down-regulated angiotensin-converting enzyme 2 (ACE2) expression, excessive inflammatory response, hypoxia and adverse drug reaction, are closely related to the occurrence and development of the course of COVID-19. In combination with recently published medical data of patients having SARS-CoV-2 infection and the latest studies, the manifestations of damage to cardiovascular system by COVID-19, possible pathogenic mechanisms and advances of the treatment are proposed in this article.

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Immunomodulatory properties of captopril, an ACE inhibitor, on LPS-induced lung inflammation and fibrosis as well as oxidative stress

Cited by 42 publications

References 50 publications

Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19

Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19

A hypothesis for pathobiology and treatment of COVID‐19: The centrality of ACE1/ACE2 imbalance

Mechanisms and treatments of myocardial injury in patients with corona virus disease 2019

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