scholarly journals Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline

2014 ◽  
Vol 124 (3) ◽  
pp. 1000-1012 ◽  
Author(s):  
Kenneth E. Bernstein ◽  
Yosef Koronyo ◽  
Brenda C. Salumbides ◽  
Julia Sheyn ◽  
Lindsey Pelissier ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Converting Enzyme ◽  
Enzyme Overexpression

Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

2018 ◽  
Vol 15 (4) ◽  
pp. 386-398 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Enzyme Inhibitors ◽  
Late Onset ◽  
Amyloid Β ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Alzheimer’S Disease Dementia

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

scholarly journals Angiotensin-converting Enzyme Overexpression in Mouse Myelomonocytic Cells Augments Resistance toListeriaand Methicillin-resistantStaphylococcus aureus

2010 ◽  
Vol 285 (50) ◽  
pp. 39051-39060 ◽  
Author(s):  
Derick Okwan-Duodu ◽  
Vivekanand Datta ◽  
Xiao Z. Shen ◽  
Helen S. Goodridge ◽  
Ellen A. Bernstein ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Myelomonocytic Cells ◽  
Enzyme Overexpression

Abstract 13940: Using an Angiotensin Converting Enzyme Inhibitor to Treat Cardiovascular and Cognitive Decline in a Rat Model of Vascular Dementia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
JENNIFER SHEARON ◽  
Rachel Fenner ◽  
Yulia Grigorova ◽  
Ross McDevitt ◽  
Samuel Ajamu ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spatial Memory ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Control Treatment ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
And Control

Background: Aged Dahl salt sensitive rats (DSS) rats represent a model of vascular dementia, i.e., they develop central arterial stiffness (CAS), hypertension, and cognitive decline. DSS rats have compromised renin-angiotensin system (RAS) which is activated with age and contributes to hypertension. This study examined whether angiotensin converting enzyme (ACE) inhibitor, lisinopril, affects CAS and cognitive functions in aged male DSS (n=26). Methods & Results: Following initial measurements at 16-mo of age (baseline; BL), DSS were administered lisinopril through their water (LISI; 15mg/kg/day, n=11) or control treatment (n=15) for 2-mo. Pulse wave velocity (PWV), a marker of CAS, and systolic blood pressure (SBP) were measured at BL and at 18-mo of age. Open field test (OFT) to assess anxiety-like behavior and Morris water maze (MWM) to assess spatial memory were performed at 18-mo, then aortae and hearts were collected and weighed. Aortic wall collagen abundance was estimated by histochemistry. Statistical analyses were performed by 2-way ANOVA mixed effects model and t-test. The data are presented as mean ± SEM. At 18-mo of age, control animals had high SBP similar to BL (187±4 vs. 184±7 mmHg), while LISI-treated DSS had lower SBP by 39±4 mmHg vs. BL (p<0.01). PWV in control rats increased from 16 to 18-mo (7.0±0.6 vs. 10.8±1.0 m/s; p<0.05), while PWV in LISI-treated DSS decreased after 2-mo of treatment (7.1±0.3 vs. 5.4±0.3 m/s; p<0.01). Lower heart weights (2.9±0.1 vs. 3.7±0.3 g/kg BW; p<0.01), aortic weights (4.4±0.1 vs. 5.0±0.2 mg/mm/kg BW; p<0.01), and aortic medial collagen abundance (14.0±0.3 vs. 19.6±1.0 % of total; p<0.01) were observed in the LISI-treated rats vs. control rats. No differences between LISI-treated and control groups at 18-mo (38±10 vs. 25±6 cm traveled in center) were found in OFT. MWM results indicated that neither group at 18-mo of age was able to learn the task and therefore could not be accurately assessed for differences in spatial memory. Conclusion: Initiation of anti-hypertensive treatment in old age was effective in reducing aortic fibrosis and lowering SBP and PWV in DSS rats. Longer treatment may be needed to improve cognitive function in this model of vascular dementia. Supported by the NIH/NIA Intramural Research Program

scholarly journals Angiotensin-converting enzyme overexpression in myelocytes enhances the immune response

2014 ◽  
Vol 395 (10) ◽  
pp. 1173-1178 ◽  
Author(s):  
Kenneth E. Bernstein ◽  
Romer A. Gonzalez-Villalobos ◽  
Jorge F. Giani ◽  
Kandarp Shah ◽  
Ellen Bernstein ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Immune Response ◽  
Renal Function ◽  
Alzheimer Disease ◽  
Angiotensin Converting Enzyme ◽  
Pressure Control ◽  
Converting Enzyme ◽  
Monocytic Cells ◽  
Effective Immune Response ◽  
Enzyme Overexpression

Abstract Angiotensin-converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis, and several aspects of the immune response. ACE 10/10 mice overexpress ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization toward a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with melanoma, bacterial infection, or Alzheimer disease. As shown in ACE 10/10 mice, enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges.

scholarly journals Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension

2009 ◽  
Vol 169 (13) ◽  
pp. 1195 ◽  
Author(s):  
Kaycee M. Sink ◽  
Xiaoyan Leng ◽  
Jeff Williamson ◽  
Stephen B. Kritchevsky ◽  
Kristine Yaffe ◽  
...  
Keyword(s):  
Older Adults ◽  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors
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