Fingerprint Profile of Alcohol‐Associated Heart Failure in Human Hearts

Haddad, Georges E.; Saunders, Lori; Carles, Maria; Crosby, Seth D.; Monte, Federica del; MacGillivray, Thomas E.; Semigran, Marc J.; Dec, G. William; Hajjar, Roger J.; Doye, Angelia A.; Glass, Rita; El, Margo; Gwathmey, Judith K.

doi:10.1111/j.1530-0277.2008.00628.x

Cited by 8 publications

(9 citation statements)

References 49 publications

(54 reference statements)

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“…In that regard, microarray studies performed on cardiac tissue from alcoholic human males showed a down‐regulation in key extracellular matrix genes like titin, collagen type III, and calponin. These data allude to alcohol‐induced etiology of heart failure (Haddad et al., ).…”

Section: Pathogenesis Of Alcohol‐induced Cardiomyopathymentioning

confidence: 97%

The Good, the Bad, and the Ugly with Alcohol Use and Abuse on the Heart

Walker

Cousins

Umoh

et al. 2013

Alcoholism Clin & Exp Res

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Since its advent, alcohol has been utilized throughout history socially, for rituals, worship, for its therapeutic, antibacterial, and analgesic properties. In moderation, alcohol consumption and its use are generally viewed as clinically beneficial. Excessive alcohol consumption on the other hand has been recognized as having several adverse implications. Excessive use increases the risk of liver and heart disease, metabolic disturbances, nutritional deficiencies, certain cancers, brain damage, dementia, neuropathy, as well as other facets of morbidity and mortality. This review targets the sequelae of alcohol consumption on the heart, specifically on myocardial contractility, calcium channel signaling, and intracellular signaling pathways. With the incidence of alcohol-induced cardiac abnormalities being higher than previously thought, it is of increasing importance to elucidate the mechanisms behind them. Here the cardiac effects of alcohol were not discussed in isolation but in conjunction with other important factors, such as HDL and LDL levels and vascular dilatory influences. We explore these mechanisms, in particular, the oxidative stress as the major contributor, as well as pathways that may prove to be cardioprotective. As such, we demonstrate the involvement of Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/ NRF2) as well as Akt, that act as regulators of oxidative balance during oxidative stress responses. Thus, alcohol consumption may confer a cardioprotective effect when used in moderation through an Akt/NRF2-dependent mechanism.

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Section: Pathogenesis Of Alcohol‐induced Cardiomyopathymentioning

confidence: 97%

The Good, the Bad, and the Ugly with Alcohol Use and Abuse on the Heart

Walker

Cousins

Umoh

et al. 2013

Alcoholism Clin & Exp Res

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“…Adversely, chronic HA consumption has various detrimental effects leading to alcoholic cardiomyopathy (Krenz and Korthuis, 2012). Our laboratory and others have linked the Akt pathway as a mediator of alcohol-induced translational diminishment of anti-apoptotic signals (Chen et al, 2000; Haddad et al, 2008). Akt pathway has been heavily studied with its association with induced oxidative stress (Ma and Wang, 2012), which may be linked to cardiomyopathy.…”

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confidence: 99%

Acute Alcohol Modulates Cardiac Function as PI3K/Akt Regulates Oxidative Stress

Umoh

Walker

AlRubaiee

et al. 2014

Alcohol Clin Exp Res

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Background Clinical manifestations of alcohol abuse on the cardiac muscle include defective contractility with the development of heart failure. Interestingly, low alcohol consumption has been associated with reduced risk of cardiovascular disease. Although several hypotheses have been postulated for alcoholic cardiomyopathy and for the low-dose beneficial cardiovascular effects, the precise mechanisms and mediators remain largely undefined. We hypothesize that modulation of oxidative stress by PI3K/Akt plays a key role in the cardiac functional outcome to acute alcohol exposure. Methods Thus, acutely exposed rat cardiac tissue and cardiocytes to low (LA: 5 mM), moderate (MA: 25 mM), and high (HA: 100 mM) alcohol were assessed for markers of oxidative stress in the presence and absence of PI3K/Akt activators (IGF-1 0.1 μM or constitutively active PI3K: Ad.BD110 transfection) or inhibitor (LY294002 1 μMor Akt-negative construct Ad.Akt(K179M) transfection). Results Acute LA reduced Akt, superoxide dismutase (SOD-3) and NFκB, ERK1, and p38 MAPK gene expression. Acute HA only increased that of SOD-3 and NFκB. These effects were generally inhibited by Ad.Akt(K179M) and enhanced with Ad.BD110 transfection. In parallel, LA reduced but HA enhanced Akt activity, which was reversed by IGF-1 and inhibited by Ad.Akt(K179M), respectively. Also, LA reduced caspase 3/7 activity and oxidative stress, while HA increased both. The former was blocked, while the latter effect was enhanced by Ad.Akt(K179M). The reverse was true with PI3K/Akt activation. This translated into reduced viability with HA, with no effect with LA. On the functional level, acute LA improved cardiac output and ejection fraction, mainly through increased stroke volume. This was accompanied with enhanced end-systolic pressure–volume relationship and preload recruitable stroke work. Opposite effect was recorded for HA. LA and HA in vivo functional effects were alleviated by LY and enhanced by IGF-1 treatment. Conclusions Acute LA and HA seem to oppositely affect cardiac function through modulation of oxidative stress where PI3K/Akt plays a pivotal role.

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“…The clinical relevance of this fi nding is unclear, however. Although excessive alcohol consumption is recognized as a cause of HF (Haddad et al, 2008), light to moderate alcohol consumption (up to one drink daily for women and one or two drinks daily for men) seems benefi cial in preventing CAD and CAD-related HF in healthy persons (Djousse and Gaziano, 2007;Klatsky et al, 2005;O'Keefe et al, 2007). However, because alcohol consumption increases blood pressure and thereby hypertension risk in a dose-dependent fashion (Beilin and Puddey, 2006), it may be speculated that benefi ts of moderate alcohol consumption on CAD might be counterbalanced in HF patients who are more vulnerable to blood pressure effects (Klatsky, 2004;Klatsky and Gunderson, 2006;Walsh et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Increases in B-Type Natriuretic Peptide After Acute Mental Stress in Heart Failure Patients Are Associated With Alcohol Consumption

Wirtz¹,

Redwine²,

Hong³

et al. 2010

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: The aim of this study was to investigate in heart failure (HF) patients whether acute mental stress induces increases in the HF-severity biomarker B-type natriuretic peptide (BNP) and if alcohol consumption is associated with such stress-induced increases. Method: Twenty-one male HF patients and 19 male non-HF controls (M = 56 years, SEM = 2) underwent a 15-minute acute mental stress test combining public speaking and mental arithmetic. Plasma levels of BNP were determined immediately before as well as 2 hours after the stress test. Alcohol consumption was assessed by self-reported number of drinks per month and history of use. Results: HF patients had higher BNP levels before and after stress, F(1, 38) = 23.42, p < .001, and showed greater stress-induced increases in BNP levels, F(1, 38) = 4.52, p = .04, compared with controls. HF status ( = .32, p = .015, R 2 = .10) and higher alcohol consumption ( = .61, p < .001, R 2 = .37) were independently associated with higher BNP stress increases. Moreover, higher alcohol consumption moderated the greater BNP stress increases in HF patients but not in controls ( = .49, p < .001, R 2 = .20), although alcohol consumption did not differ between groups. Conclusions: For individuals with HF, particularly those who drink moderate to more substantial amounts of alcohol, exposure to acute psychological stress leads to increases in circulating levels of BNP, a biomarker which is associated with increased morbidity and mortality in HF. (J. Stud. Alcohol Drugs, 71, 786-794, 2010)

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Fingerprint Profile of Alcohol‐Associated Heart Failure in Human Hearts

Cited by 8 publications

References 49 publications

The Good, the Bad, and the Ugly with Alcohol Use and Abuse on the Heart

The Good, the Bad, and the Ugly with Alcohol Use and Abuse on the Heart

Acute Alcohol Modulates Cardiac Function as PI3K/Akt Regulates Oxidative Stress

Increases in B-Type Natriuretic Peptide After Acute Mental Stress in Heart Failure Patients Are Associated With Alcohol Consumption

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