scholarly journals Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility

2021 ◽  
Vol 135 (15) ◽  
pp. 1805-1824
Author(s):  
Nayara Azinheira Nobrega Cruz ◽  
Danielle Stoll ◽  
Dulce Elena Casarini ◽  
Mariane Bertagnolli
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Maternal Circulation ◽  
Disease Manifestation ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
The Impact

Abstract In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto–maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin–angiotensin system (RAS) and the kallikrein–kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.

scholarly journals Kallikrein–kinin system as the dominant mechanism to counteract hyperactive renin–angiotensin system

2017 ◽  
Vol 95 (10) ◽  
pp. 1117-1124 ◽  
Author(s):  
Domenico Regoli ◽  
Fernand Gobeil
Keyword(s):  
Renin Angiotensin System ◽  
Biologically Active ◽  
Ang Ii ◽  
Kinin System ◽  
Angiotensin System ◽  
Dominant Mechanism ◽  
Renin Angiotensin ◽  
First Choice ◽  
Kallikrein Kinin System ◽  
The Impact

The renin–angiotensin system (RAS) generates, maintains, and makes worse hypertension and cardiovascular diseases (CVDs) through its biologically active component angiotensin II (Ang II), that causes vasoconstriction, sodium retention, and structural alterations of the heart and the arteries. A few endogenous vasodilators, kinins, natriuretic peptides, and possibly angiotensin (1-7), exert opposite actions and may provide useful therapeutic agents. As endothelial autacoids, the kinins are potent vasodilators, active natriuretics, and protectors of the endothelium. Indeed, the kallikrein–kinin system (KKS) is considered the dominant mechanism for counteracting the detrimental effects of the hyperactive RAS. The 2 systems, RAS and KKS, are controlled by the angiotensin-converting enzyme (ACE) that generates Ang II and inactivates the kinins. Inhibitors of ACE can reduce the impact of Ang II and potentiate the kinins, thus contributing to restore the cardiovascular homeostasis. In the last 20 years, ACE-inhibitors (ACE-Is) have become the drugs of first choice for the treatments of the major CVDs. ACE-Is not only reduce blood pressure, as sartans also do, but by protecting and potentiating the kinins, they can reduce morbidity and mortality and improve the quality of life for patients with CVDs. This paper provides a brief review of the literature on this topic.

Tissue kallikrein deficiency and renovascular hypertension in the mouse

2009 ◽  
Vol 296 (5) ◽  
pp. R1385-R1391 ◽  
Author(s):  
Violaine Griol-Charhbili ◽  
Laurent Sabbah ◽  
Juliana Colucci ◽  
Marie-Pascale Vincent ◽  
Véronique Baudrie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Tissue Kallikrein ◽  
Kinin System ◽  
Kidney Blood Flow ◽  
Kallikrein Kinin System

The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK−/−) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: −90%, 2K1C-TK−/−: −93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: −65%, 2K1C-TK−/−: −66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK−/−: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK−/−: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK−/−: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK−/−: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK−/− mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK−/−: +21%). 2K1C-TK+/+ and 2K1C-TK−/− mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

2003 ◽  
Vol 285 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
Alvin H. Schmaier
Keyword(s):  
Cross Talk ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Kinin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Two Systems ◽  
Kallikrein Kinin System

Understanding the physiological role of the plasma kallikrein-kinin system (KKS) has been hampered by not knowing how the proteins of this proteolytic system, when assembled in the intravascular compartment, become activated under physiological conditions. Recent studies indicate that the enzyme prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin-angiotensin system (RAS) indicates a novel interaction between these two systems. This interaction, along with the roles of angiotensin converting enzyme, cross talk between bradykinin and angiotensin-( 1 – 7 ) action, and the opposite effects of activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma KKS counterbalances the RAS. This review examines the interaction and cross talk between these two protein systems. This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions.

scholarly journals Kinins and Kinin Receptors in Cardiovascular and Renal Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 240
Author(s):  
Jean-Pierre Girolami ◽  
Nadine Bouby ◽  
Christine Richer-Giudicelli ◽  
Francois Alhenc-Gelas
Keyword(s):  
Experimental Studies ◽  
Physiological Role ◽  
Renal Diseases ◽  
Kinin System ◽  
Genetic Studies ◽  
Pharmacological Manipulation ◽  
Kininase Ii ◽  
Kinin Receptors ◽  
Kallikrein Kinin System

This review addresses the physiological role of the kallikrein–kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.

scholarly journals A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 370
Author(s):  
Umair Iqbal ◽  
Ravirajsinh N. Jadeja ◽  
Harshit S. Khara ◽  
Sandeep Khurana
Keyword(s):  
Hepatic Encephalopathy ◽  
Protein Intake ◽  
Alternative Therapy ◽  
Case Series ◽  
Current Evidence ◽  
Branch Chain Amino ◽  
The Impact ◽  
Protein Diets

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis.

Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation

1991 ◽  
Vol 260 (2) ◽  
pp. G213-G219 ◽  
Author(s):  
R. A. DeLa Cadena ◽  
K. J. Laskin ◽  
R. A. Pixley ◽  
R. B. Sartor ◽  
J. H. Schwab ◽  
...  
Keyword(s):  
Cell Wall ◽  
Acute Phase ◽  
Bacterial Cell ◽  
Chronic Phase ◽  
Bacterial Cell Wall ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
Bacterial Products

The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation. Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation. Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels. High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis. Factor XI levels were decreased only during the acute phase. Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase. PG-APS failed to activate the contact system in vitro. Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important.

scholarly journals The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4462
Author(s):  
Konstantinos G. Kyriakoulis ◽  
Anastasios Kollias ◽  
Garyphallia Poulakou ◽  
Ioannis G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Severe Pneumonia ◽  
Hospitalized Patients ◽  
Current Evidence ◽  
Adjusted Risk ◽  
Risk Of Death ◽  
The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

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