TMAO: how gut microbiota contributes to heart failure. Zhang Yixin,Wang Yuan,Ke Bingbing,Du Jie Translational research : the journal of laboratory and clinical medicine An increasing amount of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathologic processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gut-TMAO-HF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research. 10.1016/j.trsl.2020.08.007

Heart Failure and Liver Disease: Cardiohepatic Interactions. Xanthopoulos Andrew,Starling Randall C,Kitai Takeshi,Triposkiadis Filippos JACC. Heart failure Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation, autoimmunity, infections) and because of complex cardiohepatic interactions. The latter, which are the focus of this review, include the development of acute cardiogenic liver injury and congestive hepatopathy in HF as well as cardiac dysfunction and failure in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and sequelae following liver transplantation. The emerging role of altered liver X receptor signaling in the pathogenesis of HF comorbidities as well as of the intestinal microbiome and its metabolites in HF and liver disease are fruitful areas for future research. 10.1016/j.jchf.2018.10.007

Nonalcoholic fatty liver disease and cardiovascular disease phenotypes. Bisaccia Giandomenico,Ricci Fabrizio,Mantini Cesare,Tana Claudio,Romani Gian Luca,Schiavone Cosima,Gallina Sabina SAGE open medicine Nonalcoholic fatty liver disease is increasingly recognized as a major global health problem. Intertwined with diabetes, metabolic syndrome, and obesity, nonalcoholic fatty liver disease embraces a spectrum of liver conditions spanning from steatosis to inflammation, fibrosis, and liver failure. Compared with the general population, the prevalence of cardiovascular disease is higher among nonalcoholic fatty liver disease patients, in whom comprehensive cardiovascular risk assessment is highly desirable. Preclinical effects of nonalcoholic fatty liver disease on the heart include both metabolic and structural changes eventually preceding overt myocardial dysfunction. Particularly, nonalcoholic fatty liver disease is associated with enhanced atherosclerosis, heart muscle disease, valvular heart disease, and arrhythmias, with endothelial dysfunction, inflammation, metabolic dysregulation, and oxidative stress playing in the background. In this topical review, we aimed to summarize current evidence on the epidemiology of nonalcoholic fatty liver disease, discuss the pathophysiological links between nonalcoholic fatty liver disease and cardiovascular disease, illustrate nonalcoholic fatty liver disease-related cardiovascular phenotypes, and finally provide a glimpse on the relationship between nonalcoholic fatty liver disease and cardiac steatosis, mitochondrial (dys)function, and cardiovascular autonomic dysfunction. 10.1177/2050312120933804

Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia: therapeutic potential of resveratrol. Aubin Marie-Claude,Lajoie Claude,Clément Robert,Gosselin Hugues,Calderone Angelino,Perrault Louis P The Journal of pharmacology and experimental therapeutics It remains presently unknown whether vascular reactivity is impaired and whether maladaptive cardiac remodeling occurs before the onset of overt obesity and in the absence of hyperlipidemia. Normal female rats were fed a high-fat diet for 8 weeks and were associated with a modest nonsignificant increase of body weight (standard diet, 300 +/- 10, versus high-fat diet, 329 +/- 14 g) and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 +/- 7 mm Hg) and diastolic blood pressures (109 +/- 3) were increased compared to a standard diet (systolic blood pressure, 134 +/- 8; diastolic blood pressure, 96 +/- 5 mm Hg), and acetylcholine-dependent relaxation of isolated aortic rings (high-fat diet, 22 +/- 5%, versus standard diet, 53 +/- 8%) was significantly reduced. Furthermore, perivascular fibrosis was detected in the heart of rats fed a high-fat diet. The exogenous addition of resveratrol (trans-3,5,4'-trihydroxystilbene) (0.1 microM) to aortic rings isolated from rats fed a high-fat diet restored acetylcholine-mediated relaxation (47 +/- 9%). The administration of resveratrol (20 mg/kg/day for 8 weeks) to rats fed a high-fat diet prevented the increase in blood pressure and preserved acetylcholine-dependent relaxation of isolated aortic rings. However, resveratrol therapy failed to attenuate the perivascular fibrotic response. These data have demonstrated that a high-fat diet fed to normal female rats can elicit a hypertensive response and induce perivascular fibrosis before the development of overt obesity and in the absence of hyperlipidemia. Resveratrol therapy can prevent the hypertensive response in female rats fed a high-fat diet but is without effect on the progression of perivascular fibrosis. 10.1124/jpet.107.135061