Login
Search
Search
0 Dates
2024
2023
2022
2021
2020
2019
2018
0 Events
CPC 2018
CPC 2019
Curso de Atualização em Medicina Cardiovascular 2019
Reunião Anual Conjunta dos Grupos de Estudo de Cirurgia Cardíaca, Doenças Valvulares e Ecocardiografia da SPC
CPC 2020
CPC 2021
CPC 2022
CPC 2023
CPC 2024
0 Topics
A. Basics
B. Imaging
C. Arrhythmias and Device Therapy
D. Heart Failure
E. Coronary Artery Disease, Acute Coronary Syndromes, Acute Cardiac Care
F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
G. Aortic Disease, Peripheral Vascular Disease, Stroke
H. Interventional Cardiology and Cardiovascular Surgery
I. Hypertension
J. Preventive Cardiology
K. Cardiovascular Disease In Special Populations
L. Cardiovascular Pharmacology
M. Cardiovascular Nursing
N. E-Cardiology / Digital Health, Public Health, Health Economics, Research Methodology
O. Basic Science
P. Other
0 Themes
01. History of Cardiology
02. Clinical Skills
03. Imaging
04. Arrhythmias, General
05. Atrial Fibrillation
06. Supraventricular Tachycardia (non-AF)
07. Syncope and Bradycardia
08. Ventricular Arrhythmias and Sudden Cardiac Death (SCD)
09. Device Therapy
10. Chronic Heart Failure
11. Acute Heart Failure
12. Coronary Artery Disease (Chronic)
13. Acute Coronary Syndromes
14. Acute Cardiac Care
15. Valvular Heart Disease
16. Infective Endocarditis
17. Myocardial Disease
18. Pericardial Disease
19. Tumors of the Heart
20. Congenital Heart Disease and Pediatric Cardiology
21. Pulmonary Circulation, Pulmonary Embolism, Right Heart Failure
22. Aortic Disease
23. Peripheral Vascular and Cerebrovascular Disease
24. Stroke
25. Interventional Cardiology
26. Cardiovascular Surgery
27. Hypertension
28. Risk Factors and Prevention
29. Rehabilitation and Sports Cardiology
30. Cardiovascular Disease in Special Populations
31. Pharmacology and Pharmacotherapy
32. Cardiovascular Nursing
33. e-Cardiology / Digital Health
34. Public Health and Health Economics
35. Research Methodology
36. Basic Science
37. Miscellanea
0 Resources
Abstract
Slides
Vídeo
Report
CLEAR FILTERS
ß-3 adrenoceptors: a therapeutic target for pulmonary arterial hypertension
Session:
Sessão de Comunicações Orais - Ciência Básica
Speaker:
Pedro Ferreira
Congress:
CPC 2020
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.4 Basic Science - Vascular Biology and Physiology
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Pedro Ferreira; Birger Tielemans; Allard Wagenaar; Rui Adão; Adelino Leite-Moreira; Carmen Brás Silva; Chantal Dessy; Jean-Luc Balligand; Rozenn Quarck; Marion Delcroix; Catharina Belge
Abstract
<p><strong>Introduction</strong>: Pulmonary Arterial Hypertension (PAH) is an incurable disease with a poor prognosis. Currently available therapies exclusively act as pulmonary vasodilators, and only slightly increase survival. PAH is defined by a mean pulmonary arterial pressure (mPAP) >20 mmHg, a pulmonary arterial wedge pressure ≤15 mmHg and a pulmonary vascular resistance (PVR) ≥3 Wood units. It is characterized by a pre-capillary arteriopathy including vascular remodelling and plexiform lesions, resulting in increased PVR, right ventricular (RV) hypertrophy, progressive right heart failure and ultimately death. The β-3 adrenergic receptor (β3AR), thought to be restricted to adipocytes, is expressed in the heart and pulmonary vessels. Stimulating β3ARs, using approved drugs that specifically activate this receptor (mirabegron), has shown benefits in experimental left ventricular (LV) heart failure. Despite that, it's effects in PAH are still unknown.</p> <p><strong>Hypothesis:</strong> Due to the vasoactive and cardioprotective effects of β3AR agonists, we hypothesize that activating this receptor could provide a double target effect, serving as a new treatment for PAH.</p> <p><strong>Methods</strong>: Employing a translational approach, we first quantified the expression of β3AR in pulmonary tissue from patients and rats with PAH. Using the monocrotaline (MCT)- -induced PAH model, we determined the acute and chronic effects of BRL37344 and mirabegron (intravenous and orally available β3AR agonists, respectively), using telemetry (DSI dual pressure), high resolution transthoracic echocardiography (Vevo 2100) and pressure-volume analysis. Finally, we determined the effects and mechanisms of mirabegron in isolated small pulmonary arteries (myography).</p> <p><strong>Results</strong>: Both human and rat lung tissue expresses the β3AR, and while its expression (mRNA) was decreased in tissue from PAH patients, no differences were observed in the animal model. Acute administration of BRL37344 increased cardiac output (CO) in both control and MCT animals, without affecting PAP, reducing PVR. Treatment with mirabegron in telemetry- -implanted animals was safe and resulted in increased heart rate, without affecting RV pressures or causing hypotension. An initial protocol showed no beneficial effects using low-dose mirabegron, while high dose treatment with a clinically available form (Betmiga™, Astellas Pharma) attenuated the development of MCT-induced PAH, and significantly improved RV and LV diastolic function. Finally, mirabegron induced relaxation of small pulmonary arteries, isolated from both control or MCT animals, in a β1/β2 AR-independent, and nitric oxide-dependent manner.</p> <p><strong>Conclusion</strong>: With our work, we have shown that β3AR agonists are a safe and efficient therapy for experimental PAH, opening the door for the repurposing of these drugs to PAH patients.</p>
Slides
Video
Our mission: To reduce the burden of cardiovascular disease
Visit our site