Alcoholic cardiomyopathy: an update European Heart Journal
Abl1 is an important mediator of the genomic responses to doxorubicin treatment. Although Abl1 itself does not function as a transcription factor, this tyrosine kinase operates as a co-activator and modulates transcriptional responses through its interaction with multiple targets, with p53 playing a decisive role in doxorubicin-induced apoptosis. Consistent with its known activity in the elongation phase of gene transcription through tyrosine phosphorylation of RNA Pol II CTD [199, 200], Abl1 could then be proposed alcoholic cardiomyopathy to act coordinatively in the transcriptional modulation of doxorubicin-regulated genes. Our study extends the growing list of Abl1 functions that ranges from survival signaling, proliferation and programmed cell death. Hence, fine-tuning and modulation of Abl1 kinase activities may represent a protective mechanism to ameliorate doxorubicin unwanted side effects. Additonally, we observed significant downregulation of interferon-induced protein with tetratricopeptide repeats 3 (Ifit3) in T4 treated animals.
- The left ventricular end-diastolic diameters show a significant increase in such patients compared to healthy individuals in the same age and weight.
- Conversely, p53 represses the E2 ubiquitin-conjugating enzyme Ube2c [106], and its inhibition sensitizes breast cancer cells to the DNA damaging effects of doxorubicin [107].
- The germinal centers are vanished, and the marginal zone is considerably shrunken with nests of small aggregates of p73 positive cells.
Laboratory Studies
In his 1906 textbook The Study of the Pulse, William MacKenzie described cases of heart failure attributed to alcohol and first used the term “alcoholic heart disease” [26]. While most genes involved in the inflammatory response are upregulated, a few are repressed, especially in T1. Of particular interest is Prkn (Parkin RBR E3 Ubiquitin protein ligase) and Nlrp6 (NLR family pyrin domain-containing 6). As already mentioned, Parkin prevents stress-mediated cell death by ubiquitination of NEMO, which results in an NF-κB mediated upregulation of OPA1, thereby inhibiting apoptosis [164].
Treatment of ACM
The datasets supporting the conclusions of this article are included within the article and its additional files. The type of treatment depends on the type of cardiomyopathy and how serious it is. List of the 15 articles reviewed in this study, indicating the study authors, objectives, design, sample size, patient characteristics, experimental procedures, outcome measures, and main findings.
- Various pathophysiological mechanisms have been postulated in the development of cardiomyopathy however one key factor undergoing active research is the role of genetic mutation and susceptibility to develop cardiomyopathy.
- When reactive oxygen species (ROS) are produced in excessive manners due to heavy alcohol consumption, it damages mitochondrial DNA, resulting in mitochondrial injuries.
- Gross morphological examination and histopathology revealed diminished thicknesses of the chamber walls with the left and the right ventricles displaying features of dilative cardiomyopathy (Fig. 1D, lines 1&2).
- More than 1.8 million individuals in Germany with a total population of 81 million inhabitants are alcohol dependant.
- In addition to these, stem-cell therapy tries to improve myocyte regeneration [112,152].
Analysis of genomic data
Others have also found a significant decrease in intramitochondrial isocitrate dehydrogenase activity (20,24). Others have found an increased level of fatty acid ethyl esters in the alcoholic heart, which can attach to the mitochondria and disrupt mitochondria respiratory function https://ecosoberhouse.com/ (32). Chronic ethanol misuse clearly depresses protein synthesis and degradation, involving both structural and non-structural heart proteins [104,128]. At a pathological level, sarcomere Z-line distortion and disruption of the sarcomere pattern leads to myocytolysis [107,129].
Cell lines and culture culture
Notably, in patients with a history of chronic alcohol consumption complicated by significant myocardial dysfunction and chronic malnutrition, re-feeding syndrome may increase the cardiac dysfunction. Therefore, physicians should be aware of the risk of new cardiomyopathy in patients with these overlapping diagnoses [144]. Control of these alcohol-related systemic diseases, as well as the strict control of the presence of other heart risk factors (tobacco, cocaine, arterial hypertension, diabetes mellitus, or anemia) contributes to ACM improvement [10,20,23,37,52]. Atrial fibrillation should be controlled with chronotropic drugs such as digoxin or diltiazem and anticoagulant treatment to avoid arterial embolisms [60,145]. One of the relevant facts in ACM is the existence of a clear gender difference, women being more susceptible to the toxic effects of alcohol than men at the same level of lifetime ethanol consumption [93,94]. This fact has been assessed with echocardiographic monitoring in women consuming high doses of ethanol both in the subclinical period of disease [46] as well as in the clinical period when congestive heart failure appears [95].
Subsequently, we employed a matrix generation tool which is integrated into the BIOBASE tool MATCH™. Supplementary Table S1 shows the PWMs which we used to interrogate promoter sequences for Abl1 and p53 consensus binding sites of doxorubicin regulated genes. The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity. Another nutritional factor classically involved in the pathophysiology of AC was cobalt excess. The ‘Quebec beer drinkers’ cardiomyopathy’ was related to cobalt supplementation to beer that was made in the past. It was described as a form of DCM with severe pericardial effusion, low cardiac output, and purplish skin coloration.