Impact of ACE 2 genetic variant on antidepressant efficacy of SSRIs

2021 ◽  
pp. 1-25
Author(s):  
Negar Firouzabadi ◽  
Parisa Farshadfar ◽  
Maral Haghnegahdar ◽  
Ali Alavi-Shoushtari ◽  
Vahid Ghanbarinezhad
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Genetic Variant ◽  
Rating Scale ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Brain Functions ◽  
Mas Receptor ◽  
Pcr Rflp ◽  
Antidepressant Efficacy

Abstract Backgrounds Identification of a new axis of angiotensin converting enzyme 2 (ACE2)/angiotensin (1–7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE 2 catabolizes angiotensin II and produces angiotensin (1-7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin1-7 receptor) exhibit anxiety-like behaviors. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to Selective Serotonin Reuptake Inhibitors (SSRIs). Methods In a randomized control trial, two hundred newly diagnosed Iranian patients with major depressive disorder (MDD) completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression (HAM-D) score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction (PCR-RFLP) method. Results The A allele as well as AA and GA genotypes were significantly associated with better response to SSRIs (P=0.008; OR= 3.4; 95%CI=1.4-8.5 and P=0.027; OR=3.3, 95%CI=1.2-9.2 respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (P=0.0002; OR=9.1; 95%CI=2.4-33.7). The A allele was significantly associated with better response to sertraline (P=0.0001; OR=7.6; 95%CI=2.5-23.3). Conclusions In conclusion our results confirm the role of G8790A in response to some SSRIs.

scholarly journals ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good

2011 ◽  
Vol 300 (4) ◽  
pp. R804-R817 ◽  
Author(s):  
Ping Xu ◽  
Srinivas Sriramula ◽  
Eric Lazartigues
Keyword(s):  
Neurological Diseases ◽  
Renin Angiotensin System ◽  
Transgenic Animals ◽  
Angiotensin Iv ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor ◽  
Angiotensin Peptides ◽  
The Central Nervous System

The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1–7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT1 receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1–7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1–12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1–7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.

scholarly journals Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Roberta da Silva Filha ◽  
Sérgio Veloso Brant Pinheiro ◽  
Thiago Macedo e Cordeiro ◽  
Victor Feracin ◽  
Érica Leandro Marciano Vieira ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Renin Angiotensin System ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Ang Ii ◽  
Cross Sectional ◽  
Angiotensin Converting Enzyme 2 ◽  
Inflammatory Molecules

AbstractIntroduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

scholarly journals ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19

2020 ◽  
Vol 134 (22) ◽  
pp. 3047-3062
Author(s):  
Koichi Yamamoto ◽  
Hikari Takeshita ◽  
Hiromi Rakugi
Keyword(s):  
Skeletal Muscle ◽  
Transmembrane Protein ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Potential Contribution ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
Potential Association ◽  
Entry Receptor

Abstract Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. In the renin–angiotensin system (RAS), ACE2 cleaves angiotensin II (Ang II) into angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. Previous studies have provided abundant evidence suggesting that Ang 1-7 modulates multiple signalling pathways leading to protection from pathological muscle remodelling and muscle insulin resistance. In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.

scholarly journals Association between angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin-II receptor 1 (AGTR1) polymorphisms and COVID-19 infection in the southeast of Iran: a preliminary case-control study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hamid Reza Kouhpayeh ◽  
Farhad Tabasi ◽  
Mohammad Dehvari ◽  
Mohammad Naderi ◽  
Gholamreza Bahari ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Iranian Population ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Pcr Rflp ◽  
Severity Of The Disease

Abstract Background The COVID-19 pandemic remains an emerging public health crisis with serious adverse effects. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV--2) infection, targeting angiotensin-converting enzyme-2 (ACE2) receptor for cell entry. However, changes in the renin-angiotensin system (RAS) balance alter an individual’s susceptibility to COVID-19 infection. We aimed to evaluate the association between AGT rs699 C > T, ACE rs4646994 I/D, and AGTR1 rs5186 C > A variants and the risk of COVID-19 infection and the severity in a sample of the southeast Iranian population. Methods A total of 504 subjects, including 258 COVID-19 positives, and 246 healthy controls, were recruited. Genotyping of the ACE gene rs4646994, and AGT rs699, and AGTR1 rs5186 polymorphisms was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. Results Our results showed that the II genotype of ACE rs4646994 and the I allele decreased the risk of COVID-19 infection. Moreover, we found that the TC genotype and C allele of AGT rs699 increased the risk of COVID-19 infection. The AGTR1 rs5186 was not associated with COVID-19 infection. Also, we did not find any association between these polymorphisms and the severity of the disease. However, we found a significantly higher age and prevalence of diabetes and hypertension in patients with severe disease than a non-severe disease. Conclusions These findings suggest that ACE rs4646994 and AGT rs699 polymorphisms increase the risk of COVID-19 infection in a southeast Iranian population.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

The Renin-Angiotensin System and the Cerebrovascular Diseases: Experimental and Clinical Evidence

2020 ◽  
Vol 27 (6) ◽  
pp. 463-475 ◽  
Author(s):  
Lucas M. Kangussu ◽  
Lucas Alexandre Santos Marzano ◽  
Cássio Ferraz Souza ◽  
Carolina Couy Dantas ◽  
Aline Silva Miranda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Renin Angiotensin System ◽  
Cerebrovascular Diseases ◽  
Therapeutic Effects ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

Cerebrovascular Diseases (CVD) comprise a wide spectrum of disorders, all sharing an acquired or inherited alteration of the cerebral vasculature. CVD have been associated with important changes in systemic and tissue Renin-Angiotensin System (RAS). The aim of this review was to summarize and to discuss recent findings related to the modulation of RAS components in CVD. The role of RAS axes is more extensively studied in experimentally induced stroke. By means of AT1 receptors in the brain, Ang II hampers cerebral blood flow and causes tissue ischemia, inflammation, oxidative stress, cell damage and apoptosis. On the other hand, Ang-(1-7) by stimulating Mas receptor promotes angiogenesis in brain tissue, decreases oxidative stress, neuroinflammation, and improves cognition, cerebral blood flow, neuronal survival, learning and memory. In regard to clinical studies, treatment with Angiotensin Converting Enzyme (ACE) inhibitors and AT1 receptor antagonists exerts preventive and therapeutic effects on stroke. Besides stroke, studies support a similar role of RAS molecules also in traumatic brain injury and cerebral aneurysm. The literature supports a beneficial role for the alternative RAS axis in CVD. Further studies are necessary to investigate the therapeutic potential of ACE2 activators and/or Mas receptor agonists in patients with CVD.

Neuromodulatory role of angiotensin-(1–7) in the central nervous system

2013 ◽  
Vol 125 (2) ◽  
pp. 57-65 ◽  
Author(s):  
Mariela M. Gironacci ◽  
Nadia A. Longo Carbajosa ◽  
Jorge Goldstein ◽  
Bruno D. Cerrato
Keyword(s):  
Renin Angiotensin System ◽  
Cardiovascular Effects ◽  
Synaptic Cleft ◽  
Neutral Endopeptidase ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
The Central Nervous System ◽  
Release Characteristic ◽  
Transporter Expression

Ang-(1–7) [angiotensin-(1–7)] constitutes an important functional end-product of the RAS (renin–angiotensin system) endogenously formed from AngI (angiotensin I) or AngII (angiotensin II) through the catalytic activity of ACE2 (angiotensin-converting enzyme 2), prolyl carboxypeptidase, neutral endopeptidase or other endopeptidases. Ang-(1–7) lacks the pressor, dipsogenic or stimulatory effect on aldosterone release characteristic of AngII. In contrast, it produces vasodilation, natriuresis and diuresis, and inhibits angiogenesis and cell growth. At the central level, Ang-(1–7) acts at sites involved in the control of cardiovascular function, thus contributing to blood pressure regulation. This action may result from its inhibitory neuromodulatory action on NE [noradrenaline (norepinephrine)] levels at the synaptic cleft, i.e. Ang-(1–7) reduces NE release and synthesis, whereas it causes an increase in NE transporter expression, contributing in this way to central NE neuromodulation. Thus, by selective neurotransmitter release, Ang-(1–7) may contribute to the overall central cardiovascular effects. In the present review, we summarize the central effects of Ang-(1–7) and the mechanism by which the peptide modulates NE levels in the synaptic cleft. We also provide new evidences of its cerebroprotective role.

scholarly journals The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function

2010 ◽  
Vol 298 (6) ◽  
pp. F1297-F1305 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Jasmina Varagic
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Therapeutic Interventions ◽  
Experimental Hypertension ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
A Site

The study of experimental hypertension and the development of drugs with selective inhibitory effects on the enzymes and receptors constituting the components of the circulating and tissue renin-angiotensin systems have led to newer concepts of how this system participates in both physiology and pathology. Over the last decade, a renewed emphasis on understanding the role of angiotensin-(1–7) and angiotensin-converting enzyme 2 in the regulation of blood pressure and renal function has shed new light on the complexity of the mechanisms by which these components of the renin angiotensin system act in the heart and in the kidneys to exert a negative regulatory influence on angiotensin converting enzyme and angiotensin II. The vasodepressor axis composed of angiotensin-(1–7)/angiotensin-converting enzyme 2/mas receptor emerges as a site for therapeutic interventions within the renin-angiotensin system. This review summarizes the evolving knowledge of the counterregulatory arm of the renin-angiotensin system in the control of nephron function and renal disease.

Expression of an angiotensin-(1–7)-producing fusion protein produces cardioprotective effects in rats

2004 ◽  
Vol 17 (3) ◽  
pp. 292-299 ◽  
Author(s):  
Robson A. S. Santos ◽  
Anderson J. Ferreira ◽  
Ana Paula Nadu ◽  
Aline N. G. Braga ◽  
Alvair Pinto de Almeida ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Cardiac Contractility ◽  
Renin Angiotensin System ◽  
Transgenic Rats ◽  
Specific Expression ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Cardioprotective Effects ◽  
Hemodynamic Measurements

Angiotensin-(1–7) [ANG-(1–7)] is a recently described heptapeptide product of the renin-angiotensin system. Because biosynthesis of ANG-(1–7) increases in animals treated with cardioprotective drugs and inactivation of the gene for angiotensin converting enzyme 2 [an enzyme involved in the biosynthesis of ANG-(1–7)] leads to the development of cardiac dysfunction, it has been suggested that ANG-(1–7) has cardioprotective properties. To directly test this possibility, we have generated transgenic rats that chronically overproduce ANG-(1–7) by using a novel fusion protein methodology. TGR(A1–7)3292 rats show testicular-specific expression of a cytomegalovirus promoter-driven transgene, resulting in a doubling of circulating ANG-(1–7) compared with nontransgenic control rats. Radiotelemetry hemodynamic measurements showed that transgenic rats presented a small but significant increase in daily and nocturnal heart rate and a slight but significant increase in daily and nocturnal cardiac contractility estimated by dP/d t measurements. Strikingly, TGR(A1–7)3292 rats were significantly more resistant than control animals to induction of cardiac hypertrophy by isoproterenol. In addition, transgenic rats showed a reduced duration of reperfusion arrhythmias and an improved postischemic function in isolated Langendorff heart preparations. These results support a cardioprotective role for circulating ANG-(1–7) and provide a novel tool for evaluating the functional role of ANG-(1–7).

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