Study of the Expression of Autophagy Markers in the Myocardium in Patients With Persistent or Permanent Atrial Fibrillation
- Conditions
- Atrial Fibrillation
- Interventions
- Other: Sampling
- Registration Number
- NCT05850039
- Lead Sponsor
- Ospedale San Raffaele
- Brief Summary
Atrial Fibrillation (AFib) is the most common cardiac arrhythmia, causing the loss of the normal and coordinated atrial contractility.
Several studies have demonstrated the existence of some atrial anatomical sites involved in the initiation and maintenance of this arrhythmia, first of all the posterior wall in the area around the outlet of the pulmonary veins. In fact, the existence of a complex of structural and functional modifications has been documented, collectively defined as "structural remodeling" which involve both the cardiomyocyte and the interstitium (the space between the cardiomyocytes) from a histopathological point of view; at the cardiomyocyte level, a loss of sarcomeres in the perinuclear site (myocytolysis), a reduction in the expression of "adult" cellular proteins (e.g. cardiotin and titin) with concomitant re-expression of "fetal" proteins (e.g. muscle actin smooth), as well as a modification of the mitochondrial structure. At the interstitial level, remodeling is characterized by the deposition of fibrous tissue in the interstitium between the muscle bundles and by a reduction in capillary density. Regarding the deposition of collagen fibers, some studies on an experimental model of AFib have shown that the latter is not reversible.
Autophagy is an intracellular process regulated by numerous biochemical signals; it is present at basal levels in most tissues and allows the physiological turnover of the various structural components of the cell, directing them to lysosomal degradation. It can also be stimulated by external signals in unfavorable environmental conditions, such as in the case of pathologies that determine a condition of tissue oxidative stress protracted over time. Experimentally, an excessive activation of the latter has been associated with the early stages of pathological cardiac remodeling in various animal models of cardiovascular diseases and some recent studies have hypothesized that altered levels of autophagy may contribute to the possible mechanisms involved in the generation and maintenance of the remodeling cardiomyocyte and interstitial structure in AFib. The levels of autophagic activity can be evaluated by studying specific markers - such as the Beclin-1 and LC3B proteins - constituents of the autophagic signaling cascade. In the case of LC3B, the "LC3BII/LC3BI" ratio (the processed form of autophagosomal vesicles and the unprocessed form constitutively present at the cytoplasmic level) was used as an autophagy biomarker. Furthermore, some microRNAs (miRNAs) capable of controlling the expression of proteins of the autophagic cascade have been described in the literature. This is the case of miRNA 30a and miRNA 204, respectively, which respectively inhibit the expression of Beclin-1 and of LC3B.
This study aims to investigate from a histo-morphological and molecular point of view the presence of alterations of autophagy mechanisms in patients with persistent or permanent AFib and which correlate these modifications with the degree of structural remodeling present at the level of the left atrial myocardium.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 81
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Study group Sampling Patients with permanent or persistent AFib, undergoing surgical ablation, isolated or concomitant to valve surgery Autoptic control group Sampling Autopsy samples in subjects without arrhythmia Mitral surgery control group Sampling Patients undergoing isolated or concomitant mitral valve surgery
- Primary Outcome Measures
Name Time Method Beclin-1 and LC3B levels in blood Baseline
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
IRCCS Ospedale San Raffaele
🇮🇹Milan, Italy