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![Cardiopulmonary Protective Role of Probiotics and the ACE2/ANG-(1-7)/MAS Axis of the Renin-Angiotensin System için kapak resmi Cardiopulmonary Protective Role of Probiotics and the ACE2/ANG-(1-7)/MAS Axis of the Renin-Angiotensin System için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
Cardiopulmonary Protective Role of Probiotics and the ACE2/ANG-(1-7)/MAS Axis of the Renin-Angiotensin System
Başlık:
Cardiopulmonary Protective Role of Probiotics and the ACE2/ANG-(1-7)/MAS Axis of the Renin-Angiotensin System
Yazar:
Jeffrey, Colleen Therese Cole, author.
ISBN:
9780438120617
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (224 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Özet:
Cardiopulmonary disease remains a leading cause of death globally and in the United States. As such, research into effective therapies for cardiopulmonary disease is imperative. The studies in this dissertation have investigated novel approaches for treatment of two related cardiopulmonary diseases: heart failure (HF) and pulmonary hypertension (PH).
Current treatments for HF and PH focus on reducing symptoms and improving quality of life rather than treating the underlying causes of disease. To that end, it is well-known that the health of the cardiopulmonary systems is linked to the reninangiotensin system (RAS) and that a balance between the vasodeleterious (ACE/AngII/AT1R) and vasoprotective (ACE2/Ang-(1-7)/MasR) components of the RAS is critical for cardiopulmonary homeostasis. We propose that cardiopulmonary disease is a state of RAS imbalance, in which the vasodeleterious components outweigh the vasoprotective, and that augmentation of vasoprotective ACE2 and Ang-(1-7) would be beneficial to cardiopulmonary disease. Recent work showing a role for ACE2 in gut physiology led us to speculate that the therapeutic effects of RAS may be partially mediated by actions on the gastrointestinal tract and/or gut microbiome. Furthermore, emerging data has demonstrated an association between gut microbiota dysbiosis and cardiopulmonary disease, suggesting that restoration of the gut microbiome may prove beneficial.
This project tested the hypotheses that (1) the protective RAS axis restores function in endothelial progenitor cells (EPCs) from HF patients; (2) oral feeding of the probiotic Lactobacillus paracasei (LP) attenuates symptoms of PH; and (3) genetic modification of LP to express Ang-(1-7) provides further benefit to PH therapy. We observed improved function in EPCs from HF patients following treatment with Ang-(1- 7). We also found that feeding with LP prevented the increases in right ventricular systolic pressure and hypertrophy that are characteristic of PH. This was associated with changes in inflammatory status and gut microbiota composition. Furthermore, feeding of LP expressing Ang-(1-7) provided additional protection against PH. The studies presented here highlight the importance of the protective RAS in cardiovascular disease, explore a role for gut microbiota in cardiopulmonary health, and introduce an innovative approach to target both the RAS and gut microbiota for treatment of cardiopulmonary disease.
Notlar:
School code: 0070
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(696603.1) | 696603-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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