Correction: Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

Dalpiaz, EP. L. M.; Lamas, Aline Zandonadi; Caliman, Izabela Facco; Ribeiro, Rogério Faustino; Abreu, Gláucia Rodrigues de; Moysés, Margareth Ribeiro; Andrade, Tadeu Uggere de; Gouvêa, Sônia Alves; Alves, Márcio Fernando Madureira; Carmona, Adriana K.; Bissoli, Nazaré Souza

doi:10.1371/journal.pone.0133225

Cited by 16 publications

(14 citation statements)

References 1 publication

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“…activity in the left ventricle of the SHR (12,13). However, in contrast to observing no change in the normotensive mouse kidney, orchiectomy markedly decreased the activity of ACE2 in the left ventricle by 7-fold.…”

Section: Heart and Vasculaturementioning

confidence: 72%

“…Sex also impacts the pathophysiological regulation of cardiac ACE2 activity. ACE2 activity was higher in the left ventricle of male SHR compared to their female littermates (12,13). A longitudinal study of the effect of myocardial infarction on the RAS in male and female Wistar rats showed that Ace2 mRNA was up-regulated in the left ventricular penumbra in both sexes;…”

Section: Heart and Vasculaturementioning

confidence: 95%

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Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19

Stanic

Maddox

Souza

et al. 2021

American Journal of Physiology-Regulatory, Integrative and Comp

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Throughout the world, including the United States, men have worse outcomes from COVID-19 than women. SARS-CoV-2, the causative virus of the COVID-19 pandemic, uses angiotensin-converting-enzyme-2 (ACE2) to gain cellular entry. ACE2 is a member of the renin-angiotensin-system (RAS) and plays an important role in counteracting the harmful effects mediated by the angiotensin-type-1-receptor. Therefore, we conducted Ovid MEDLINE and Embase database searches of basic science studies investigating the impact of the biological variable of sex on ACE2 expression and regulation from 2000, the year ACE2 was discovered, through December 31, 2020. Out of 2131 publications, we identified 853 original research articles on ACE2 conducted in primary cells, tissues and/or whole mammals excluding humans. The majority (68.7%) of these studies that cited the sex of the animal were conducted in males, while 11.2% were conducted solely in females; 9.26% compared ACE2 between the sexes, while 10.8% did not report the sex of the animals used. General findings are that sex-differences are tissue-specific and when present, are dependent-upon gonadal state. Renal, cardiac and adipose ACE2 is increased in both sexes under experimental conditions that model co-morbidities associated with worse COVID-19 outcomes including hypertension, obesity, and renal and cardiovascular diseases; however, ACE2 protein was generally higher in the males. Studies in Ace2- knockout-mice indicate ACE2 plays a greater role protecting the female from developing hypertension than the male. Studying the biological variable of sex in ACE2 research provides an opportunity for discovery in conditions involving RAS-dysfunction and will shed light on sex-differences in COVID-19-severity.

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Section: Heart and Vasculaturementioning

confidence: 72%

Section: Heart and Vasculaturementioning

confidence: 95%

Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19

Stanic

Maddox

Souza

et al. 2021

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

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“…The only known stimuli of TMPRSS2 gene transcription are androgens, and hospitalized COVID-19 patients exhibited androgenic alopecia ( 305 ). E 2 -treated NHBE cells expressed lower levels of ACE2 mRNA ( 306 ), while ovariectomy (loss of E 2 ) increased ACE2 activity, and orchiectomy (loss of androgens) decreased enzyme activity ( 292 , 307 , 308 ). Further studies correlating sex hormones to ACE2 are needed.…”

Section: Secondary Risk Factorsmentioning

confidence: 99%

Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies

Pathangey

Fadadu

Hospodar

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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On March 11, 2020, the World Health Organization declared COVID-19 a pandemic, and the reality of the situation has finally caught up to the widespread reach of the disease. The presentation of the disease is highly variable, ranging from asymptomatic carriers to critical COVID-19. The availability of angiotensin-converting enzyme 2 (ACE2) receptors may reportedly increase the susceptibility and/or disease progression of COVID-19. Comorbidities and risk factors have also been noted to increase COVID-19 susceptibility. In this paper, we hereby review the evidence pertaining to ACE2's relationship to common comorbidities, risk factors, and therapies associated with severe and critical COVID-19. We also highlight gaps of knowledge that require further investigation. The primary comorbidities of respiratory disease, cardiovascular disease, renal disease, diabetes, obesity, and hypertension had strong evidence. The secondary risk factors of age, sex, and genetics had limited-to-moderate evidence. The tertiary factors of ACE inhibitors and angiotensin II receptor blockers had limited-to-moderate evidence. Ibuprofen and thiazolidinediones had limited evidence.

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“…The presence of a single X chromosome in men (in contrast to XX in women) could predispose to reduced alternative mechanisms for protection upon exposure to the virus. Notably, ACE-2 gene is located on X chromosomes and is affected by androgens (116)(117)(118)(119), thus accounting for a higher susceptibility to infection in men. On the contrary, estrogen can down regulate the expression of ACE-2 in differentiated airway epithelial cells (120).…”

Section: Sex Steroid Hormones and Covid-19mentioning

confidence: 99%

COVID-19: Integrating the Complexity of Systemic and Pulmonary Immunopathology to Identify Biomarkers for Different Outcomes

et al. 2021

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In the last few months, the coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and has provoked an exceptional effort from the scientific community to understand the disease. Clinical evidence suggests that severe COVID-19 is associated with both dysregulation of damage tolerance caused by pulmonary immunopathology and high viral load. In this review article, we describe and discuss clinical studies that show advances in the understanding of mild and severe illness and we highlight major points that are critical for improving the comprehension of different clinical outcomes. The understanding of pulmonary immunopathology will contribute to the identification of biomarkers in an attempt to classify mild, moderate, severe and critical COVID-19 illness. The interface of pulmonary immunopathology and the identification of biomarkers are critical for the development of new therapeutic strategies aimed to reduce the systemic and pulmonary hyperinflammation in severe COVID-19.

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Correction: Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

Cited by 16 publications

References 1 publication

Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19

Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19

Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies

COVID-19: Integrating the Complexity of Systemic and Pulmonary Immunopathology to Identify Biomarkers for Different Outcomes

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