Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

Vecchiola, Andrea; Fuentes, César M.; Solar, Isidora; Lagos, Carlos F.; Opazo, María Cecilia; Muñoz‐Durango, Natalia; Riedel, Claudia A.; Owen, Gareth I.; Kalergis, Alexis M.; Fardella, Carlos E.

doi:10.3389/fendo.2020.00223

Cited by 17 publications

(19 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In summary, the majority of studies points to an increase in ACE2 expression after MRB treatment, mainly by counteracting aldosterone-induced down regulation of ACE2. In addition, mitigation of the deleterious effects of obesity on the RAS, possibly reducing obesity-related COVID-19 complications ( Feraco et al, 2013 ; Vecchiola et al, 2020 ) and direct anti-inflammatory and antiviral effects of MRBs, could be beneficial in the treatment of pulmonary COVID-19 complications ( Cadegiani, Wambier, & Goren, 2020 ). Importantly, MRBs such as spironolactone possess a significant anti-androgenic activity, which may be beneficial in the context of SARS-CoV-2 infection, by inhibiting the androgen-dependent expression of “Transmembrane protease, serine 2” (TMPRSS2), a transmembrane protease crucial for SARS-CoV-2 entry ( Liaudet & Szabo, 2020 ).…”

Section: Cardiovascular Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

View full text Add to dashboard Cite

The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

show abstract

Section: Cardiovascular Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…In addition to the protection reported to be provided by spironolactone, specific actions against SARS-CoV-2 actions have been proposed, including increased availability of free circulating ACE2 in response to a hyperreninemic state induced by MR antagonism [98][99][100][101][102][103][104], reduction of TMPRSS2 expression due to antagonism of AR [105][106][107], reversal of RAAS abnormalities induced by obesity [108,109], and possible direct antiinflammatory and anti-viral actions that hamper lung injuries [110][111][112][113][114][115][116][117][118][119][120][121]. There are currently three ongoing clinical trials with spironolactone [122][123][124].…”

Section: Of Moderate Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

View full text Add to dashboard Cite

Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

show abstract

“…At vascular level, the activation of these channels in the endothelial cells seem to also be the possible mechanism through which aldosterone can mediate the vascular damage in the context of obesity, since specific deletion of endothelial ENaC prevents endothelial stiffness, impaired eNOS activation, aortic fibrosis and remodeling in obese mice through the modulation of vascular oxidative stress and inflammatory response [ 31 ]. Finally, it is worth mentioning that the blockade of MR is accompanied by an improvement of the metabolic consequences of obesity [ 156 , 176 , 177 , 178 ] and, as we have already mentioned, can participate in the vascular damage in the context of obesity [ 152 , 153 ].…”

Section: Mechanisms Involved In Vascular Alterations Associated Wimentioning

confidence: 99%

Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest

et al. 2021

View full text Add to dashboard Cite

The vascular system plays a central role in the transport of cells, oxygen and nutrients between different regions of the body, depending on the needs, as well as of metabolic waste products for their elimination. While the structure of different components of the vascular system varies, these structures, especially those of main arteries and arterioles, can be affected by the presence of different cardiovascular risk factors, including obesity. This vascular remodeling is mainly characterized by a thickening of the media layer as a consequence of changes in smooth muscle cells or excessive fibrosis accumulation. These vascular changes associated with obesity can trigger functional alterations, with endothelial dysfunction and vascular stiffness being especially common features of obese vessels. These changes can also lead to impaired tissue perfusion that may affect multiple tissues and organs. In this review, we focus on the role played by perivascular adipose tissue, the activation of the renin-angiotensin-aldosterone system and endoplasmic reticulum stress in the vascular dysfunction associated with obesity. In addition, the participation of oxidative stress in this vascular damage, which can be produced in the perivascular adipose tissue as well as in other components of the vascular wall, is updated.

show abstract

Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

Cited by 17 publications

References 68 publications

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Repurposing existing drugs for COVID-19: an endocrinology perspective

Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest

Contact Info

Product

Resources

About