Abstract P2103: Cannabidiol Protects Cardiac Function In Vivo And Inhibits Endothelial-to-mesenchymal Transition In Vitro : A Potential Anti-fibrotic Therapy For Heart Failure
| Autor: | Muthu Kumar Krishnamoorthi, Forughalsadat Sanaee, Afsaneh Lavasanifar, Keith Youker, Arvind Bhimaraj |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Circulation Research. 131 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/res.131.suppl_1.p2103 |
| Popis: | Introduction: Cannabidiol (CBD) has been investigated for application in various diseases including cardiovascular ailments. Endothelial-to-Mesenchymal transition (EndoMT) has been reported to contribute to cardiac fibrosis and eventually heart failure (HF). Here we demonstrate that both free (f) and nanoparticle encapsulated (n) CBD preserves cardiac function in a non-ischemic mouse model of HF. Further, we show that CBD inhibits EndoMT in vitro . Hypothesis: CBD administration will improve cardiac function by targeting anti-fibrotic mechanisms. Methods: HF was induced in a 3-month old C57BL/6J mice (n=3) with 1% NaCl, 0.3 mg/mL L-NAME and an osmotic pump infusion of angiotensin II (Ang II). Both fCBD and nCBD were administered twice per week subcutaneously and echocardiography and histology evaluated at 5 weeks. We used an in vitro EndoMT model with L-NAME+ Ang II as EndoMT inducers in HUVECs. CBD at 0.1, 1 and 2 μM was used to study the dose impact. Results: HF mice treated with fCBD, and nCBD exhibited significantly higher EF when compared to untreated HF mice (Fig. 1 A). Histological evaluation showed that nCBD treated group displayed a higher anti-fibrotic activity compared to fCBD (both with less fibrosis compared to HF mice) (Fig. 1 B). In vitro , when CBD was added during EndoMT induction, the transition process was inhibited. Immunofluorescence studies exhibited a dose dependent effect of CBD in inhibiting Vimentin (mesenchymal marker) expression during the EndoMT process (Fig. 1 C). Conclusion: In conclusion, CBD protects cardiac function and exhibits an anti-fibrotic effect, possibly mediated by EndoMT inhibition. A nano formulation of CBD might have a more potent impact. |
| Databáze: | OpenAIRE |
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