Targeting angiotensin-converting enzyme 2 as a new therapeutic target for cardiovascular diseases

2014 ◽  
Vol 92 (7) ◽  
pp. 558-565 ◽  
Author(s):  
Nirmal Parajuli ◽  
Tharmarajan Ramprasath ◽  
Vaibhav B. Patel ◽  
Wang Wang ◽  
Brendan Putko ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Angiotensin Converting Enzyme ◽  
Therapeutic Target ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Heart Failure Patients ◽  
Positive Effects ◽  
Mas Receptor

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several vasoactive peptides, including angiotensin II (Ang-II; a vasoconstrictive/proliferative peptide), which it converts to Ang-(1–7). Ang-(1–7) acts through the Mas receptor to mediate vasodilatory/antiproliferative actions. The renin–angiotensin system involving the ACE–Ang-II–Ang-II type-1 receptor (AT1R) axis is antagonized by the ACE2–Ang-(1–7)–Mas receptor axis. Loss of ACE2 enhances adverse remodeling and susceptibility to pressure and volume overload. Human recombinant ACE2 may act to suppress myocardial hypertrophy, fibrosis, inflammation, and diastolic dysfunction in heart failure patients. The ACE2–Ang-(1–7)–Mas axis may present a new therapeutic target for the treatment of heart failure patients. This review is mainly focused on the analysis of ACE2, including its influence and potentially positive effects, as well as the potential use of human recombinant ACE2 as a novel therapy for the treatment cardiovascular diseases, such as hypertension and heart failure.

scholarly journals Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and Renin-Angiotensin Peptides in SARS-CoV-2 Mediated Mortality and End-Organ Injuries

Hypertension ◽  
2021 ◽  
Author(s):  
Kaiming Wang ◽  
Mahmoud Gheblawi ◽  
Anish Nikhanj ◽  
Matt Munan ◽  
Erika MacIntyre ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Tumor Necrosis Factor Receptor ◽  
Renin Angiotensin System ◽  
Adverse Outcomes ◽  
Blood Collection ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Angiotensin Peptides

ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline blood collection at admission and repeated sampling at 7 days. The primary outcome was 90-day mortality, and secondary outcomes were the incidence of end-organ injuries. Overall, 242 patients were included, the median age was 63 (52–74) years, 155 (64.0%) were men, and 57 (23.6%) patients reached the primary end point. Baseline soluble ACE2 was elevated in COVID-19 but was not associated with disease severity or mortality. In contrast, an upward trajectory of soluble ACE2 at repeat sampling was independently associated with an elevated risk of mortality and incidence of acute myocardial injury and circulatory shock. Similarly, an increase in soluble tumor necrosis factor receptor levels was also associated with adverse outcomes. Plasma Ang I, Ang 1-7 (angiotensin 1–7) levels, and the Ang 1-7/Ang II (angiotensin II) ratio were elevated during SARS-CoV-2 infection related to downregulation of ACE activity at baseline. Moreover, patients having an upward trajectory of soluble ACE2 were characterized by an imbalance in the Ang 1-7/Ang II ratio. The observed dysregulation of ACE2 and angiotensin peptides with disease progression suggest a potential role of ADAM17 inhibition and enhancing the beneficial Ang 1-7/Mas axis to improve outcomes against SARS-CoV-2 infection.

scholarly journals ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Basic Science ◽  
Physiological Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Multifunctional Protein ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

scholarly journals Overexpression of Central ACE2 (Angiotensin-Converting Enzyme 2) Attenuates the Pressor Response to Chronic Central Infusion of Ang II (Angiotensin II)

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1514-1525
Author(s):  
Anyun Ma ◽  
Lie Gao ◽  
Ahmed M. Wafi ◽  
Li Yu ◽  
Tara Rudebush ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Pressor Response ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Intracerebroventricular Infusion

We investigated the mechanism by which ACE2 (angiotensin-converting enzyme 2) overexpression alters neurohumoral outflow and central oxidative stress. Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is a master antioxidant transcription factor that regulates cytoprotective and antioxidant genes. We hypothesized that upregulation of central ACE2 inhibits the pressor response to Ang II (angiotensin II) by reducing reactive oxygen species through a Nrf2/antioxidant enzyme–mediated mechanism in the rostral ventrolateral medulla. Synapsin human Angiotensin Converting Enzyme 2 positive (SynhACE2 +/+ ) mice and their littermate controls synhACE2 −/− were used to evaluate the consequence of intracerebroventricular infusion of Ang II. In control mice, Ang II infusion evoked a significant increase in blood pressure and norepinephrine excretion, along with polydipsia and polyuria. The pressor effect of central Ang II was completely blocked in synhACE2 +/+ mice. Polydipsia, norepinephrine excretion, and markers of oxidative stress in response to central Ang II were also reduced in synhACE2 +/+ mice. The MasR (Mas receptor) agonist Ang 1–7 and blocker A779 had no effects on blood pressure. synhACE2 +/+ mice showed enhanced expression of Nrf2 in the rostral ventrolateral medulla which was blunted following Ang II infusion. Ang II evoked nuclear translocation of Nrf2 in cultured Neuro 2A (N2A) cells. In synhACE2 −/− mice, the central Ang II pressor response was attenuated by simultaneous intracerebroventricular infusion of the Nrf2 activator sulforaphane; blood pressure was enhanced by knockdown of Nrf2 in the rostral ventrolateral medulla in Nrf2 floxed (Nrf2 f/f ) mice. These data suggest that the hypertensive effects of intracerebroventricular Ang II are attenuated by selective overexpression of brain synhACE2 and may be mediated by Nrf2-upregulated antioxidant enzymes in the rostral ventrolateral medulla.

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