scholarly journals Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

2021 ◽  
Vol 22 (24) ◽  
pp. 13178
Author(s):  
Duc Le ◽  
Lindsay Brown ◽  
Kundan Malik ◽  
Shin Murakami
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Heart Association ◽  
Model Systems ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Amyloid Toxicity ◽  
Age Related

A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events.

scholarly journals Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

2021 ◽  
Author(s):  
Duc Le ◽  
Lindsay Brown ◽  
Kundan Malik ◽  
Shin Murakami
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Heart Association ◽  
Model Systems ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Amyloid Toxicity ◽  
Age Related

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

scholarly journals Pharmacology of Agents Acting on the Renin-Angiotensin System

1983 ◽  
Vol 11 (4) ◽  
pp. 377-383 ◽  
Author(s):  
C. I. Johnston ◽  
B. Jackson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Reaction Pathway ◽  
Effective Means ◽  
Renin Angiotensin System ◽  
Cardiovascular Responses ◽  
Term Therapy ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin

The renin-angiotensin system is the most important hormonal system in the control of blood pressure. It can be blocked at several steps in its reaction pathway. Angiotensin-converting enzyme, or kininase II, is responsible for catalysing the formation of vasoconstrictor angiotensin II as well as for the breakdown of the vasodilator bradykinin. With the advent of specific orally active angiotensin-converting enzyme inhibitors (captopril and enalapril) a practical and effective means of blocking angiotensin formation is now clinically available. ACE inhibitors are effective long-term therapy in patients with essential hypertension. They are particularly useful in the treatment of severe accelerated drug-resistant hypertension and renovascular hypertension, and the agents of choice for afterload reduction in severe congestive cardiac failure. They have several pharmacological advantages, important in anaesthetic practice, over other hypotensive agents. They have no central nervous or autonomic nervous system effects. Thus, patients being treated with ACE inhibitors retain normal sympathetic cardiovascular responses.

scholarly journals Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney

2020 ◽  
Author(s):  
Xiao Jiang ◽  
James M. Eales ◽  
David Scannali ◽  
Alicja Nazgiewicz ◽  
Priscilla Prestes ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Individual Risk ◽  
Human Tissues ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Age Related ◽  
Renal Expression

Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter individual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

scholarly journals The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus

2020 ◽  
Vol 23 (3) ◽  
pp. 242-249
Author(s):  
O. K. Vikulova ◽  
Zamira Zuraeva ◽  
L. V. Nikankina ◽  
M. V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Viral Infection ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. Thisreview presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE inhibitors and ARBs therapy on the disease outcome, and presents theperspectives of the treatment with recombinant ACE 2.

scholarly journals Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney

2020 ◽  
Vol 41 (48) ◽  
pp. 4580-4588
Author(s):  
Xiao Jiang ◽  
James M Eales ◽  
David Scannali ◽  
Alicja Nazgiewicz ◽  
Priscilla Prestes ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Human Tissues ◽  
Converting Enzyme ◽  
Antihypertensive Medications ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Age Related ◽  
Renal Expression

Abstract Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

Resveratrol ameliorates the cyclosporine-induced vascular and renal impairments: possible impact of the modulation of renin–angiotensin system

2019 ◽  
Vol 97 (12) ◽  
pp. 1115-1123 ◽  
Author(s):  
Seldag Bekpinar ◽  
Ece Karaca ◽  
Selin Yamakoğlu ◽  
F. İlkay Alp-Yıldırım ◽  
Vakur Olgac ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Immunosuppressive Drug ◽  
Oxidative Stress Marker ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Components ◽  
Renal Tubular

Cyclosporine, an immunosuppressive drug, exhibits a toxic effect on renal and vascular systems. The present study investigated whether resveratrol treatment alleviates renal and vascular injury induced by cyclosporine. Cyclosporine (25 mg/kg per day, s.c.) was given for 7 days to rats either alone or in combination with resveratrol (10 mg/kg per day, i.p.). Relaxation and contraction responses of aorta were examined. Serum levels of blood urea nitrogen, creatinine, angiotensin II, and angiotensin 1-7 were measured. Histopathological examinations as well as immunostaining for 4-hydroxynonenal and nitrotyrosine were performed in the kidney. RNA expressions of renin–angiotensin system components were also measured in renal and aortic tissues. Cyclosporine decreased the endothelium-dependent relaxation and increased vascular contraction in the aorta. It caused renal tubular degeneration and increased immunostaining for 4-hydroxynonenal, an oxidative stress marker. Cyclosporine also caused upregulations of the vasoconstrictive renin–angiotensin system components in renal (angiotensin-converting enzyme) and aortic (angiotensin II type 1 receptor) tissues. Resveratrol co-treatment prevented the cyclosporine-related deteriorations. Moreover, it induced the expressions of vasodilatory effective angiotensin-converting enzyme 2 and angiotensin II type 2 receptor in aorta and kidney, respectively. We conclude that resveratrol may be effective in preventing cyclosporine-induced renal tubular degeneration and vascular dysfunction at least in part by modulating the renin–angiotensin system.

scholarly journals Synergistic Expression of Angiotensin-Converting Enzyme (ACE) and ACE2 in Human Renal Tissue and Confounding Effects of Hypertension on the ACE to ACE2 Ratio

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2453-2457 ◽  
Author(s):  
Shigeyuki Wakahara ◽  
Tadashi Konoshita ◽  
Shinichi Mizuno ◽  
Makoto Motomura ◽  
Chikako Aoyama ◽  
...  
Keyword(s):  
Renal Function ◽  
Angiotensin Converting Enzyme ◽  
Pairwise Comparison ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Clinicopathological Variables

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

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