Therapeutic Delivery of Ang(1–7) via Genetically Modified Probiotic: A Dosing Study
| Autor: | Thomas W. Buford, Christy S. Carter, Elaine Sumners, Amrisha Verma, Drake Morgan, Gilberto O Lobaton, Victor Aquino, Mohan K. Raizada, Qiuhong Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Aging Ang-(1–7) Pharmacology Proof of Concept Study Drug Administration Schedule law.invention 03 medical and health sciences Probiotic 0302 clinical medicine law Rats Inbred BN Diabetes mellitus Renin–angiotensin system Research Practice Animals Medicine 030304 developmental biology 0303 health sciences business.industry Effector Angiotensin II Probiotics Lacticaseibacillus paracasei medicine.disease Peptide Fragments Rats Inbred F344 Recombinant Proteins Rats 3. Good health Genetically modified organism Lactobacillus Blood pressure Models Animal Recombinant DNA Dysbiosis Angiotensin-Converting Enzyme 2 Angiotensin I Pharmaceutical Vehicles Renin-angiotensin system Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |
| ISSN: | 1758-535X 1079-5006 |
| DOI: | 10.1093/gerona/glz222 |
| Popis: | In recent years a number of beneficial health effects have been ascribed to the renin-angiotensin system (RAS) that extend beyond lowering blood pressure, primarily mediated via the angiotensin-converting enzyme-2 (ACE2)/angiotensin (1–7) or Ang(1–7)/MAS receptor axis. Moreover, once thought as merely a systemic effector, RAS components exist within tissues. The highest tissue concentrations of ACE2 mRNA are located in the gut making it an important target for altering RAS function. Indeed, genetically engineered recombinant probiotics are promising treatment strategies offering delivery of therapeutic proteins with precision. An Ang(1–7) secreting Lactobacillus paracasei (LP) or LP-A has been described for regulation of diabetes and hypertension; however, we are the first to the best of our knowledge to propose this paradigm as it relates to aging. In this Research Practice manuscript, we provide proof of concept for using this technology in a well-characterized rodent model of aging: the Fisher344 x Brown Norway Rat (F344BN). Our primary findings suggest that LP-A increases circulating levels of Ang(1–7) both acutely and chronically (after 8 or 28 treatment days) when administered 3× or 7×/week over 4 weeks. Our future preclinical studies will explore the impact of this treatment on gut and other age-sensitive distal tissues such as brain and muscle. |
| Databáze: | OpenAIRE |
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