scholarly journals Correlation of ACE2 with RAS components after Losartan treatment in light of COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Javeria Zaheer ◽  
Hyeongi Kim ◽  
Jin Su Kim
Keyword(s):  
Clinical Trials ◽  
Angiotensin Receptor Blocker ◽  
Treated Patient ◽  
Protective Role ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Positive Regulation ◽  
Angiotensin Converting Enzyme 2 ◽  
Losartan Treatment

AbstractAngiotensin-converting enzyme 2 (ACE2) is an important factor in coronavirus disease (COVID-19) interactions. Losartan (LOS) belongs to the angiotensin receptor blocker (ARB) family. Additionally, the protective role of ACE2 restored by LOS has been suggested and clinically examined in the treatment of COVID-19 patients. Furthermore, clinical trials with LOS have been conducted. However, the mechanism through which LOS enhances ACE2 expression remains unclear. In addition, the response of ACE2 to LOS differs among patients. Our LOS-treated patient data revealed a correlated mechanism of ACE2 with components of the renin-angiotensinogen system. We observed a significant positive regulation of MAS1 and ACE2 expression. In the context of LOS treatment of COVID-19, ACE2 expression could depend on LOS regulated MAS1. Thus, MAS1 expression could predict the COVID-19 treatment response of LOS.

scholarly journals Heart Failure and Coronavirus Disease-19

2021 ◽  
Vol 9 (F) ◽  
pp. 176-179
Author(s):  
Refli Hasan
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blocker ◽  
Ace Inhibitor ◽  
Reciprocal Relationship ◽  
Cardiovascular Disorders ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Patients With Heart Failure ◽  
The Subject

Globally, 4.2% population suffer from heart failure. The condition has a mortality rate between 56% and 78%. Coronavirus disease-2019 (COVID-19) was first reported in December 2019 and became a pandemic since March 11, 2020. As COVID-19 emerges, cardiovascular disorders including, heart failure, become one of the most common comorbidity that increase the risk for contracting the disease. Heart failure and COVID-19 have reciprocal relationship. Patients with heart failure are at higher risk for COVID-19 with more unfavorable outcome. COVID-19 itself may deteriorate pre-existing heart failure in the subject. This situation is mediated by the presence of angiotensin converting enzyme-2 (ACE-2) in cardiac myocytes and pericytes, direct effect of viral invasion to myocytes and pericytes, downregulation of ACE-2 which hampers cardiovascular function, and uncontrolled inflammation known as cytokine storm. Prudent management, including implementation of telemedicine, continuation of ACE inhibitor and angiotensin receptor blocker, and medications’ side effects monitoring, is important in managing patients with coexisting heart failure and COVID-19.

scholarly journals The Controversy on the Role of ACE2 Receptor in COVID-19 Infection: The Protective Shift toward the ACE2 Axis

2020 ◽  
Author(s):  
Sarah I Y Ahmed
Keyword(s):  
Animal Studies ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Genetic Variations ◽  
Converting Enzyme ◽  
Organ Protection ◽  
Angiotensin Converting Enzyme 2 ◽  
Scientific Debate

Background: Angiotensin-converting enzyme 2 (ACE2)  is recognized as the main cellular receptor for the new coronavirus, SARS-CoV-2, that facilitates its entry into the host target cell, leading to the fatal viral infection, coronavirus disease 2019 (COVID-19). Thus, it is considered as a main therapeutic target in the SARS-CoV-2 infection. The dual role of ACE2 as a gate for SARS-CoV-2 virus and as a part of lung and multi-organ protection has built a scientific debate that affects the choice of treatments used against COVID-19 patient. ACE2 inhibitors like anti-ACE2 antibodies were first introduced as therapeutic solutions that, theoretically, would decrease the availability of target molecules for SARS-CoV-2 by downregulating ACE2 expression. However, animal studies showed that ACE2 upregulation acts as a counterbalance to the hypertensive pro-inflammatory angiotensin I-converting enzyme (ACE) in the renin–angiotensin system (RAS) and results in a protective role against acute lung injury – a fatal consequence of the disease. The current study tests the effect of ACE2-activating treatments against the outcome of genetic variations in the population that have ACE2-upregulatory effects. Conclusion  Despite its role as a receptor for the SARS-CoV-2 virus, experimental studies and the genetic polymorphisms in populations that have ACE2 upregulation revealed a protective role against COVID-19 infection.   Key words: ACE2   ACE  COVID-19  treatments  genetic variations

scholarly journals Sacubitril/Valsartan: The Role of Neprilysin Pathway in Heart Failure

2021 ◽  
Vol 10 (2) ◽  
pp. 133
Author(s):  
Sidhi L. Purwowiyoto ◽  
Ferina Angelia ◽  
Ananta S. Prawara
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Ace Inhibitor ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin Ii Receptor ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
Receptor Blockers

Neprilysin (NEP) is an enzyme present in several body cells and is involved in the degradation of natriuretic peptides (NPs), bradykinin (BK), and adrenomedullin (ADM). Furthermore, sacubitril/valsartan (LCZ696), the first agent of Angiotensin Receptor Neprilysin Inhibitor (ARNI), has been developed to inhibit both Renin Angiotensin Aldosterone System (RAAS) and NEP. This study, therefore, aimed to discuss the role of sacubitril/valsartan in inhibiting the progression of heart failure (HF) by influencing the RAAS and NEP pathways. Data on previous articles related to basic theory and clinical trials of ARNI were collected through multiple search engines using the inclusion criteria: articles published in the English language within 2010 to 2020, while additional information on HF guidelines, RAAS, NPs, and ADM were acquired separately. Subsequently, a total of 30 studies were selected and further discussed. According to the results, NEP inhibition leads to a rise in the level of vasodilator agents and is beneficial for HF patients previously prescribed solely RAAS inhibiting agent (Angiotensin Converting Enzyme, ACE-inhibitor and Angiotensin II Receptor Blockers, ARB). In addition, the RAAS, as well as the NEP pathways play a significant role in HF progression and are inhibited by sacubitril/valsartan. Also, clinical trials showed sacubitril/valsartan is superior to ACE-inhibitor and ARB in clinical trials in treating, as well as reducing the morbidity and mortality rates of patients suffering from HF with reduced ejection fraction (HFrEF). Keywords: ARNI, heart failure, neprilysin, sacubitril/valsartan Sacubitril/Valsartan: Peran dari Jalur Neprilisin dalam Gagal JantungAbstrakNeprilisin (NEP) merupakan sebuah enzim yang dapat ditemukan di berbagai sel pada tubuh dan terlibat dalam mendegradasi peptida natriuretik, bradykinin  (BK), dan adrenomedullin (ADM). Sacubitril/valsartan (LCZ696) merupakan agen pertama dari Angiotensin Receptor Neprilysin Inhibitor (ARNI) yang dikembangkan untuk menghambat jalur Renin Angiotensin Aldosterone System (RAAS) dan NEP. Review ini bertujuan untuk membahas peranan dari sacubitril/valsartan dalam menghambat progresi gagal jantung dengan memengaruhi jalur RAAS dan NEP. Pengumpulan data untuk teori dasar dan uji klinis ARNI dalam artikel review ini menggunakan beberapa mesin pencari. Informasi tambahan seperti pedoman-pedoman gagal jantung, RAAS, peptida natriuretik, dan ADM didapatkan secara terpisah. Kriteria inklusi yang digunakan adalah studi harus berbahasa Inggris dan dipublikasikan antara 2010 dan 2020. Sebanyak 30 studi diinklusi dan dibahas lebih lanjut dalam review ini. Hasilnya didapatkan bahwa inhibisi dari NEP menyebabkan terjadinya peningkatan agen-agen vasodilator yang berdampak positif bagi pasien gagal jantung yang sebelumnya direkomendasikan meminum obat yang hanya menghambat RAAS (penghambat Angiotensin Converting Enzyme/ACE dan Angiotensin II Receptor Blockers/ARB). Sacubitril/valsartan menghambat alur RAAS dan NEP yang mana keduanya memainkan peranan penting dalam progresi gagal jantung. Sacubitril/valsartan lebih superior dalam mencapai target pengobatan pasien yaitu mengurangi morbiditas dan mortalitas pasien gagal jantung dengan penurunan fraksi ejeksi dibandingkan dengan penghambat ACE dan ARB pada uji-uji klinis.Kata kunci: ARNI, gagal jantung, neprilisin, sacubitril/valsartan

scholarly journals Bradykinin as a Probable Aspect in SARS-Cov-2 Scenarios: Is Bradykinin Sneaking out of our Sight?

2020 ◽  
Author(s):  
Seyed-Mohammad Ghahestani ◽  
Javad Mahmoudi ◽  
Sakineh Hajebrahimi ◽  
Amir-Babak Sioofy-Khojine ◽  
Hanieh Salehi-Pourmehr ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Disease Process ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Direct Target

The new virus SARS-CoV-2 is savagely spreading out over the world. The biologic studies show that the target receptor for the virus might be angiotensin-converting enzyme 2 (ACE2). This peptide is responsible for converting angiotensin II (Ang II), which is a profoundly active peptide, into Ang 1-7 with quite a balancing barbell function. It is emphasized that the direct target of the virus is ACE2 underlining the obvious difference with ACE. Nevertheless, we hypothesized that a back load build up effect on Ang II may usurp the ACE capacity and subsequently leave the bradykinin system unabated. We think there are clinical clues for dry cough and the presumed aggravating role of ACE inhibitors like captopril on the disease process. Thereby, we speculated that inhibition of bradykinin synthesis and/or blockade of bradykinin B2 receptor using Aprotinin/ecallantide and Icatibant, respectively, may hold therapeutic promise in severe cases and these molecules can be advanced to clinical trials.

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