The Angiotensin-converting Enzyme Insertion/Deletion Polymorphism as a Common Risk Factor for Major Pregnancy Complications

Gintoni, Iphigenia; Αδαμοπούλου, Μαρία; Yapijakis, Christos

doi:10.21873/invivo.12236

Cited by 16 publications

(13 citation statements)

References 57 publications

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“…The renin-angiotensin system has a strong presence in the respiratory system mainly in the lung tissue, regulating pulmonary circulation and blood pressure, as well as lung development and function (10,12,28). RAS also plays a role in local inflammatory, oxidative, and fibrotic events and can sometimes contribute into creating a fertile soil for carcinogenesis, due to the adverse effects of the protein hormone angiotensin II, which is formed by the hydrolytic action of the ACE and counterbalanced by ACE2 and its product Ang 1-7 (13,25,26,42,43,54).…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, the Insertion/Deletion (I/D) functional polymorphism of the ACE gene may result to elevated levels of the enzyme in the plasma, tissues and the intracellular compartment. Homozygosity for the D allele (DD genotype) leads to about twice the concentration and activity of ACE compared to the homozygosity for the normal I allele (II genotype) (32)(33)(34). The I/D polymorphism has been strongly associated with many of the most serious and common lung disorders, including COPD, pulmonary hypertension, asthma, acute lung injury, lung cancer, pulmonary sarcoidosis, and it has recently been shown to influence the disease course of COVID-19, as well as the susceptibility to SARS-CoV-2 infection (35)(36)(37)(38)(39)(40)(41).…”

Section: Ras In Lung Disease: the Involvement Of Ace And Ace2mentioning

confidence: 99%

“…The hypoxic, oxidative and hypertrophic environment created by the AngII octapeptide acts favorably on carcinogenesis and the growth of tumors, while providing them with resistance to treatment and increased metastatic potential. Among many types of cancer, RAS has been shown to be highly involved in the pathogenesis of various lung cancer types (29,30,(54)(55)(56).…”

Section: Ras In Lung Disease: the Involvement Of Ace And Ace2mentioning

confidence: 99%

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The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity and mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation and blood pressure, but also contributing to normal pulmonary function and development. Angiotensin-converting enzyme (ACE) and its homologous angiotensin-converting enzyme 2 (ACE2) are considered to be amongst the main RAS regulators and are highly expressed in the pulmonary vascular endothelium. This review discusses the impact of ACE and ACE2 functional gene polymorphisms on seven major pulmonary diseases, in terms of predisposition, course, and outcome, revealing their potential utility as both genetic markers and biomarkers. The discussed conditions include chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), lung cancer and pulmonary sarcoidosis (PS), as well as SARS-CoV-2 viral infection and COVID-19 disease.Chronic respiratory diseases (CRDs) have been among the leading causes of morbidity and mortality around the globe for the last two decades (1-3). Their constantly increasing rates of occurrence may vary both between the genders, but also between different regions and socio-economic backgrounds (4). Nevertheless, the common denominator includes the deterioration of patients' quality of life that can often lead to several years of disability. The main CRDs are chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma and lung cancer, with COPD alone being the third leading cause of death worldwide, as reported in 2010 (1,5,6).On the other hand, acute lung diseases with an infectional etiology, pose a significant threat not only to lung health but also to human life (7). A recent great example is the 2019 outbreak of the novel coronavirus strain SARS-CoV-2 in China, causing the extremely infectious disease COVID-19, that led to a global pandemic and to millions of deaths, mainly due to severe respiratory complications (8, 9). So far, therapeutic approaches are mainly symptomatic, while knowledge on the exact pathogenetic mechanisms for complex lung-diseases remains limited. Consequently, prevention is predominantly based on general lifestyle guidelines, whereas the establishment of a priori personalized preventive measures, according to an individual's genetic predisposition, is still in its infancy (1, 5). Nevertheless, there are important known genetic markers that may be utilized for their predictive value.The renin-angiotensin system (RAS), in addition to its great importance for the overall homeostasis of the body, through the regulation of blood pressure and electrolyte balance, has a strong tissue-specific expression in the respiratory tract and functions both autonomously and 13 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 99%

Section: Ras In Lung Disease: the Involvement Of Ace And Ace2mentioning

confidence: 99%

Section: Ras In Lung Disease: the Involvement Of Ace And Ace2mentioning

confidence: 99%

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The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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“…Exosomes in preeclampsia. Preeclampsia (PE) represents one of the most common and significant systemic pregnancy disorders, comprising women with new onset increases of arterial blood pressure, developing mainly in the third trimester of pregnancy, as a result of various factors (53). PE prevention and reversal would be of great importance, given the high prevalence of PE, the close correlation of PE with intrauterine growth restriction (IUGR) and premature birth, and its high maternal and neonatal morbidity and mortality; 76,000 women and 500,000 neonates die each year globally because of PE (2,54).…”

Section: Exosomes In Pregnancy Complicationsmentioning

confidence: 99%

Exosomes and exosomal non‑coding RNAs throughout human gestation (Review)

et al. 2022

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In recent years, research on exosomes and their content has been intensive, which has revealed their important role in cell-to-cell communication, and has implicated exosomal biomolecules in a broad spectrum of physiological processes, as well as in the pathogenesis of various diseases. Pregnancy and its normal progression rely highly on the efficient communication between the mother and the fetus, mainly mediated by the placenta. Recent studies have established the placenta as an important source of circulating exosomes and have demonstrated that exosome release into the maternal circulation gradually increases during pregnancy, starting from six weeks of gestation. This orchestrates maternal-fetal crosstalk, including maternal immune tolerance and pregnancy-associated metabolic adaptations. Furthermore, an increased number of secreted exosomes, along with altered patterns of exosomal non-coding RNAs (ncRNAs), especially microRNAs and long non-coding RNAs (lncRNAs), have been observed in a number of pregnancy complications, such as gestational diabetes mellitus and preeclampsia. The early detection of exosomes and specific exosomal ncRNAs in various biological fluids during pregnancy highlights them as promising candidate biomarkers for the diagnosis, prognosis and treatment of numerous pregnancy disorders in adolescents and adults. The present review aimed to provide insight into the current knowledge regarding the potential, only partially elucidated, role of exosomes and exosomal cargo in the regulation and progression of normal pregnancy, as well as their potential dysregulation and contribution to pathological pregnancy situations. Contents1. Introduction 2. Exosomes 3. Exosomes in normal pregnancy 4. Exosomes in pregnancy complications 5. Clinical applications 6. Conclusions and future perspectives

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“…All these factors could lead to pregnancy loss. The D allele was also associated with a high serum ACE, which enhances the formation of angiotensin II, thus increasing the risk of thrombotic episodes and PE [ 76 ] and, ultimately, RPL [ 77 ].…”

Section: Recurrent Pregnancy Loss (Rpl)mentioning

confidence: 99%

Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism as a Conjoint Regulator of Coagulation, Fibrinolytic, and RAAS Pathway in Infertility and Associated Pregnancy Complications

Kumar¹,

Sharma

Kaur³

et al. 2022

J Renin Angiotensin Aldosterone Syst

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Despite the increase in assisted reproductive technologies, the high rates of infertility and pregnancy complications are a major concern to infertility specialists worldwide. Infertility may be attributed to pregnancy complications like thrombophilia, preeclampsia and fibrin-induced recurrent pregnancy loss (RPL). Renin-angiotensin-aldosterone system (RAAS) directly or indirectly causes preeclampsia and thrombophilia through the fibrinolytic pathway that ultimately leads to RPL or infertility. The underlying mechanisms of this interaction are still unclear. The present comprehensive review is intended to demonstrate the role and interaction of RAAS and fibrinolytic pathways in pregnancy complications. How this interaction can induce pregnancy complications, and ultimately infertility, is also discussed in the light of current evidence. This study also presents common markers that link RAAS and fibrinolytic processes in developing thrombophilia, preeclampsia and RPL. The common link in these pathways is ACE gene I/D polymorphism. Apart from ACE, PAI-1, VIIa, XIIa, AT1R, AT1AA, and TF are common molecules that can delineate the underlying causes of pregnancy complications and infertility.

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The Angiotensin-converting Enzyme Insertion/Deletion Polymorphism as a Common Risk Factor for Major Pregnancy Complications

Cited by 16 publications

References 57 publications

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Exosomes and exosomal non‑coding RNAs throughout human gestation (Review)

Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism as a Conjoint Regulator of Coagulation, Fibrinolytic, and RAAS Pathway in Infertility and Associated Pregnancy Complications

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