R&D

What is the role of beta-blockers in Pharmaceutical Treatment of Aneurysm of Ascending Thoracic Aorta? New molecular data that strengthen their role.



I ntroduction-Purpose: Pathogenesis of aneurysm of ascending thoracic aorta includes the weakening of the width of the middle tunica, which comes with a significant reduction of its' smooth muscle cells. It has been proved that the apoptosis is one of the main mechanisms that lead to reduced cellularity of the middle tunica of an aortic aneurysm. The purpose of the current study is to research the effect of chronic administration of beta-blockers in the wall of ascending aneurysmatic aorta and whether if finally the mandatory use in this specific disease is justified.
M aterials-Methods: Histological samples of normal diameter ascending thoracic aorta were collected from 31 patients who were subjected to replacement of aortic valve due to stenosis as well as from 35 patients that were subjected to replacement of ascending thoracic aorta due to aneurysm. In addition to the clinical samples, an in vitro model of cell culture of smooth muscle cells of ascending thoracic aorta of rat was used.
R esults: In the group of aortic valve stenosis 14 patients (45%) were chronically treated (treatment time > 6 months) with beta-blocker (metoprolol 50mg twice a day) while the corresponding number in the group of patients with aneurysms of ascending aorta was 16 (46%). In the subgroup of patients that were chronically treated with beta-blockers a significant increase in the expression levels of the heat shock protein HSP70it was statistically noted as well as a significant decrease of the molecular apoptosis indicators (TUNEL positive kernels, caspace-3 efficacy and Bax/Bcl2 ratio). In the in-vitro experiments the administration of metoprolol at the smooth muscle cells led to a statistically significant increase in the production of monoxide of nitrogen, at the displacement of transcriptional agent HSF1 in the kernel resulting to an increase in HSP70 synthesis with reduced phosphorylation of gene p53 that finally led to inhibition of apoptosis. When, at the same experiment, the production of monoxide of nitrogen was inhibited with the L-NAME agent, the detection of the anti-apoptosis action due to metoprolol administration, was no longer possible.
C onclusions: The current study indicates for the first time in clinical level, in the international literature, the detailed molecular mechanism of anti-apoptotic action of beta-blocker metoprolol on the smooth muscle cells of the middle tunica of ascending thoracic aorta. This effect justifies the administration of beta-blockers in patients with aneurysm of ascending thoracic aorta.

Beta-blockers

β-blockers are a class of medications that are predominately used to manage abnormal heart rhythms, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention).

They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients