We extracted total RNA with the RNeasy Kit (Qiagen) according to the manufacturer’s instructions. The human iCell® cardiomyocytes were seeded onto 96-well plates at a 70–80% confluence. Typically, we generated cDNA from 1 µg to 0.5 µg (human iCell® cardiomyocytes) of RNA by following the manufacturer’s protocol of the RevertAid M-MuLV First Strand cDNA Synthesis Kit (Fermentas, ThermoFisher Scientific, Milan, Italy). We run real-time qPCR on RotorGene 6000 (Corbett Life Science, Ancona, Italy) or CFX384 (Bio-Rad, Munich, Germany) qPCR systems by adding the Kapa SYBR green-based master mix (KapaBiosystem, Resnova, Rome, Italy) to the reaction mixture. The sequences of primers are given in supplementary Table S3, and transcript quantification is based on the ΔΔCT method with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and the β2microglobulin (B2M) as housekeeping/normalizer genes [43]. The oligonucleotide probes harbour Abl1 consensus binding sites in gene specific promoters of doxorubicin-regulated genes, and the sequences are listed in supplementary Table S2.
Data Availability
For that reason, transplant programs have very strict list requirements to qualify for a transplant and abstaining from alcohol is almost always on those lists. Alcohol-induced cardiomyopathy is a relatively uncommon condition, occurring in about 1% to 2% of people who consume more than the recommended amounts of alcohol. Alcoholic cardiomyopathy is a condition that weakens your heart and its ability to pump blood. People who suffer from alcohol dependence or alcohol use disorder (AUD) are at risk of developing this condition. Up to 42 percent of people who keep drinking alcohol after being diagnosed with alcoholic cardiomyopathy will likely die within three years.4 However, the disease may be reversible if you stop drinking alcohol.
Who is At Risk of Alcoholic Cardiomyopathy?
In the setting of acute alcohol use or intoxication, this is called holiday heart syndrome, because the incidence is increased following weekends and during holiday seasons. Based on epidemiological evidence, ACM is recognized as a significant contributor to non-ischemic DCM in Western countries. Diagnosing ACM still relies on exclusion criteria, similar to alcoholic liver disease, as excessive alcohol consumption is observed in up to 40% of DCM patients. In a national inpatient sample study, some authors have reported ACM to be most common in white males aged between 45 and 59 [2]. On physical examination, patients present with non-specific signs of congestive heart failure such as anorexia, generalized cachexia, muscular atrophy, weakness, peripheral edema, third spacing, hepatomegaly, and jugular venous distention. S3 gallop sound along with apical pansystolic murmur due to mitral regurgitation is often heard.
Short-Term Side Effects of Alcoholic Cardiomyopathy
- Therefore, we regard differences in transcriptional responses as indication for cardiomyocyte subpopulations which differed in their vulnerability to doxorubicin treatments.
- Of note, the transcript is highly responsive to TNF and therefore implicated in cytokine-dependent inflammatory and immune responses [146].
- Use of ethanol alone or ethanol with an alcohol dehydrogenase inhibitor resulted in a 25% decrease in protein synthesis.
- However, for others, the effects of alcohol-induced cardiomyopathy may be life-long.
Another study reported a protective role of Abl1 in neutralizing the inhibitory effects of Mdm2 on p53 [25]. In fact, Abl1 phosphorylates MDM2 and its posttranslational modification impairs binding of MDM2 to p53. As a result, p53 is protected from MDM2-dependent degradation, and this defines an Abl1-Mdm2-p53 signaling axis. Moreover, Abl1 may stimulate p53 activity indirectly through p38-p53-Mdm2 signaling as shown in cancer cells [26]. The natural course of ACM is mainly related to the degree of persistence in alcohol consumption and the individual biological adaptive response [2,20,41,56,81].
- Mortality in ACM is related to the progression of heart failure and malignant arrhythmias [58,65].
- Elevations in troponin can signify heart damage or an increase in cardiac output that results in demand ischemia.
- These investigators also found decreases in peroxiredoxin 5, antioxidant protein 2, and glutathione transferase 5, important anti-oxidant enzymes.
- Recently, apoptosis and necrosis have been also attributed to autophagy in ACM [18].
- However, certain symptoms may start to improve even sooner, depending on treatments and the severity of your case.
- Different pathogenic hypotheses have been suggested, such as the pivotal role of acetaldehyde [122], the role of oxidative stress and stress signaling cascades [109], and the translocation of NFkB into the nucleus [106].
- One relevant question concerning ethanol cardiac toxicity is if ethanol itself or its active metabolite acetaldehyde causes cardiac damage [73,74].
This dual effect creates an additional difficulty to achieve an effective control. Ethanol is one of the most addictive drugs for humans, with high physical and psychological addiction potential [7]. Efforts to control alcohol addiction have just 50%–60% positive results in specific cessation programs [8,9]. Still, medical professionals have not identified a specific alcohol level toxic to heart cells. They also have not established how long a person would need to consume alcohol before developing ACM. ACM is a type of heart disease that develops due to chronic alcohol consumption.
Health behaviors of adults. United States: 2005–2007
Moderate drinking below that threshold might even reduce the incidence of coronary artery disease, diabetes, and heart failure. Specifically, IL-6 is a direct transcriptional target of NF-κB, and its levels are strongly induced by TNFα [157]. Together with LIF (Leukemia Inhibitory Factor), STAT3 reinforces the pro-inflammatory responses induced by NF-κB, and the IL-6/JAK/STAT3 signaling pathway is hyperactive in inflammatory conditions [158].
- Conversely, myofibrillar degeneration, especially at an early stage, is reversible.
- If you notice any symptoms of alcoholic cardiomyopathy, seek immediate medical attention.
- Around 40–80% of people with ACM who continue drinking alcohol die within 10 years of their diagnosis.
- Under the latter conditions, autophagy via degradation of macromolecular intracellular constituents becomes important in generating and recycling carbons and amino acids.
- Interestingly, many decades ago ACM was thought to arise due to nutritional deficiency, specifically thiamine (vitamin B12).
Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca2+] transients, and structural proteins, and disrupt sarcomere contractility.
Recently, Lang and Korzick (65) reported that 20 weeks of alcohol consumption in female Fischer 344 rats increased myocardial atrogin-1 and MuRF1 expression (e.g., messenger ribonucleic acid levels). In this same study, investigators found increased markers of autophagy, such as LC3B and autophagy-related gene 7 proteins and tumor necrosis factor α, along with a reduction in mTOR activity. Autophagy is a catabolic mechanism alcoholic cardiomyopathy carried out by lysosomes and is important for the degradation of unnecessary or damaged intracellular proteins, therefore keeping the cell healthy. This mechanism is also important for cell and organism survival during stress and nutrient deprivation. Under the latter conditions, autophagy via degradation of macromolecular intracellular constituents becomes important in generating and recycling carbons and amino acids.
Symptoms of Alcoholic Cardiomyopathy
In experimental studies, acetaldehyde directly impairs cardiac contractile function [76], disrupts cardiac excitation–contraction coupling, and promotes oxidative damage and lipid peroxidation [20]. Acetaldehyde is produced at a lower quantity in the heart as compared to the liver, https://ecosoberhouse.com/ and systemic acetaldehyde does not achieve toxic heart concentrations [77]. In addition, acetaldehyde is able to interact with proteins and produce protein-adduct compounds that are highly reactive and may induce additional inflammatory and immunologic heart damage [78].
Quantity of Alcohol Intake in Cardiac Disease
The beneficial heart wine as universal remedy in medieval ages by Hildegard von Bingen [11] found its later correlates in many observations at the beginning of modern medicine when coronary artery disease (CAD) and its risk factors and symptoms received more attention. Heberden [89] described angina so elegantly in 1786 and also added that ”considerable relief“ through ”wine and spirituous liquors“ could be expected. This observation led to the erroneous belief that alcohol is an immediate coronary vasodilator. Symptomatic relief of angina could be through the anesthetic effect of ethanol or through peripheral vasodilation, which could transiently reduce oxygen demand of the heart. Alcohol abuse coinciding with myocarditis was reported in 1902 by McKenzie [26]. In endomyocardial biopsies of alcoholics up to 30 % of patients were found to exhibit sparse lymphocytic infiltrates with myocyte degeneration and focal necrosis and increased HLA (human leukocyte antigen) or ICAM (intercellular adhesion molecule) expression (Fig. 3; [16, 84]).