A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

Bernstein, Kenneth E.; Ong, Frank S; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; González-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sébastien

doi:10.1124/pr.112.006809

Cited by 273 publications

(296 citation statements)

References 501 publications

(532 reference statements)

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“…What is also of significant import from a disease perspective is that ACE2 is the receptor protein for the SARS virus. 15 Finally for a thorough discussion of the status of ACE and its inhibitors as of the end of 2012, the excellent review by Bernstein et al 16 should be consulted, to which should be added the 2014 review by Regulska et al 17 where more information on quantitative structure-activity relationship (QSAR) properties are discussed with respect to newer agents. Thus the discovery made by Brazilian pharmacologists and physicians of the activity of small peptides from the venom of Bothrops jaracaca, in the bradykinin system, has come a series of extremely important antihypertensive drugs, but have also led to a much more nuanced appreciation of what the original target protein was thought to do and what it actually does in many biological systems.…”

Section: Angiotensin Converting Enzyme Inhibitors (Ace-inhibitors)mentioning

confidence: 99%

“…However, to bring the full story to its climax, one has to return to the marine environment, as in the years from 1988 to early 2000, a significant number of sponge extracts produced molecules such as the onnamides, with onnamide F being an example (15), 30 and theopederins such as K and L (16,17). 31 Then, in 2002, Kellner 32 identified the endosymbiont as a very close relative to Pseudomonas aeruginosa and showed that interspecific transmission of the endosymbionts was related to the different genetic makeup of individual isolates.…”

Section: Brazilian Paederus Beetles and Marine Sponge Metabolitesmentioning

confidence: 99%

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The Influence of Brazilian Biodiversity on Searching for Human Use Pharmaceuticals

Newman¹

2016

J. Braz. Chem. Soc.

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This relatively short review will cover the history of some potential drug entities whose beginnings were from Brazilian flora and fauna that led to scientific findings many years later that could not even have been thought of at the time of their initial discovery. The first two are the discoveries of the effects of peptidic toxins from the highly poisonous snake Bothrops jararaca upon the control of bradykinins that led to the angiotensin converting enzyme inhibitors, and the identification of pederin from the blister beetle Paederus species that 50 plus years later led to brand new discoveries as the source of many marine sponge metabolites. All occurred well before the Convention on Biological Diversity (CBD), in 1992. Then come discussions on lapachol and its congeners and then the potential for the investigation of microbes that are associated with insects, plants and marine invertebrates and their control of the syntheses of novel metabolites with pharmaceutical potential. The review finishes with comments on the biodiversity programs that São Paulo State has put in place and how they are materially aiding in investigations of Brazilian flora and fauna but under conditions that are CBD-compliant.

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Section: Angiotensin Converting Enzyme Inhibitors (Ace-inhibitors)mentioning

confidence: 99%

Section: Brazilian Paederus Beetles and Marine Sponge Metabolitesmentioning

confidence: 99%

The Influence of Brazilian Biodiversity on Searching for Human Use Pharmaceuticals

Newman¹

2016

J. Braz. Chem. Soc.

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“…Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. (12) Angiotensin II has been implicated in a number of pathophysiologic processes with the potential to indirectly or directly influence the pathogenesis of insulin resistance and DM2. The potential mechanisms of angiotensin II-mediated insulin resistance and DM2 may include impaired blood flow and sympathetic activity, increased oxidative stress, alterations in insulin signaling, and effects on adipose tissue.…”

Section: Angiotensin Converting Enzyme Inhibitorsmentioning

confidence: 99%

Type 2 Diabetes Mellitus Prevention – Prescriptions Off-Label

Andrade

Melo

Margotto

et al. 2014

BJMHH

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The prescribing a drug without the indications for which the drug was originally approved by regulators is internationally known as prescribing "off-label". Objective: To describe the off-label prescriptions in type 2 diabetes (DM2) prevention, reported international scientific literature, through an integrative bibliographical review. Method: An integrative review was made by searching the Medline international database for review of manuscripts. Selection of these databases was based on the wide range of journals covered by each of them and our goal was to provide an overview of the scientific production devoted to the topic over the timeframe under analysis. The following inclusion criteria were considered during the review: articles published between January 1985 and June 2013; use of the keywords "off-label use" OR "off-label" OR "off-label prescribing" OR "diabetes prevention" OR "prevention" MeSH "diabetes mellitus" entered into the search form, and availability of an abstract in English. Results: A total 852 scientific productions were identified, and 30 studies were selected by contain information about the off-label prescriptions in DM2. Conclusion: The practice of off-label prescribing itself has notable benefits. In some situations, an off-label prescription is the only treatment available to a patient, either because a more targeted drug is does not exist, or because other methods of treatment are ineffective or unavailable due to patient intolerance. In these situations, off-label uses of drugs provide the only chance of restored health.

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“…ACE is essential in converting angiotensin I into angiotensin II, which is mainly an effector molecule in the renin-angiotensin system (RAS) and acts as pro-inflammatory modulator in the augmentation of immune responses. [12][13][14] The ACE I/D is a single nucleotide polymorphism (SNP) of ACE. The ACE I/D polymorphism is defined in the light of the presence (insertion, I) or absence (deletion, D) of a 287 bp repeat sequence within intron 16 of the ACE gene.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-converting enzyme insertion/deletion polymorphism associated with allergic rhinitis susceptibility: Evidence from 1410 subjects

Lin

Zheng

2013

J Renin Angiotensin Aldosterone Syst

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Background and objective: Whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene increases susceptibility to allergic rhinitis (AR) is still undetermined. Therefore, this meta-analysis was performed to systematically assess the possible association between them. Methods: The OVID, Medline, Embase, Web of Science, CNKI and Wangfang databases were searched to identify the eligible studies focusing on the association between ACE I/D polymorphism and susceptibility to AR. Results: A total of 1410 subjects from six studies were subjected to meta-analysis. In the overall analysis, ACE I/D polymorphism had a statistically significant association with increased AR risk under all genetic models (p<0.05). In the subgroup analysis by ethnicity, significant elevated AR risks were associated with ACE I/D polymorphism in Asians under all genetic models (p<0.05) and in Caucasians under under allele contrast, homozygous comparison and recessive models (p<0.05). In the subgroup analysis by age, ACE I/D polymorphism was associated with significant elevated risks of AR in adults (p<0.05) but not in children (p>0.05) under all genetic models. Conclusions:The ACE I/D polymorphism may be a risk factor for AR and studies with large sample size and representative population are warranted to verify this finding.

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A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

Cited by 273 publications

References 501 publications

The Influence of Brazilian Biodiversity on Searching for Human Use Pharmaceuticals

The Influence of Brazilian Biodiversity on Searching for Human Use Pharmaceuticals

Type 2 Diabetes Mellitus Prevention – Prescriptions Off-Label

Angiotensin-converting enzyme insertion/deletion polymorphism associated with allergic rhinitis susceptibility: Evidence from 1410 subjects

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