The Gut Microbiota and Atherosclerosis: The State of the Art and Novel Perspectives

The human gut microbiota is composed of more than 100 trillion microbes. Most communities are dominated by species belonging to the phyla Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobia. Microflora-derived short-chain fatty acids play a pivotal role in the framework of insulin resistance, obesity, and metabolic syndrome. They are an important energy source and are involved in several pathways, with proatherogenic and antiatherogenic effects. The increased gut microbiota lipopolysaccharide levels (defined as “metabolic endotoxemia”) induce a state of low-grade inflammation and are involved in atherosclerotic disease through Toll-like receptor 4. Another important inflammatory trigger in gut microbiota–mediated atherosclerotic promotion is trimethylamine N-oxide. On the other hand, protocatechuic acid was found to promote cholesterol efflux from macrophages, showing an antiatherogenic effect. Further studies to clarify specific gut composition involved in cardiometabolic syndrome and atherogenesis are needed for greater use of targeted approaches

Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective

Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis. In this review, we will examine some of the most promising novel biomarkers in HF. Inflammation plays a pivotal role in the genesis and progression of HF and, therefore, several candidate molecules have been investigated in recent years for diagnosis, prognosis, and therapy monitoring. Noncoding RNAs are attractive as biomarkers and their potential clinical applications may be feasible in the era of personalized medicine. Given the complex pathophysiology of HF, it is reasonable to expect that the future of biomarkers lies in the application of precision medicine, through wider testing panels and “omics” technologies, to further improve HF care delivery

Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD

Targeting inflammation: Impact on atherothrombosis

Atherothrombosis is a worldwide epidemic accounting for an unacceptable toll of deaths and disabilities. Its pathophysiology is complex and hardly referable to a specific mechanism; however, in the last 20 years, a growing amount of evidence has demonstrated that inflammatory processes play a major role from the very beginning to the ultimate complication of atherothrombosis. These evidences are addressing a growing interest toward anti-inflammatory agents as preventive or curative treatments of atherothrombosis. At present, accumulated data are not conclusive, but strong evidence exists in favor of an anti-inflammatory positive effect for several drugs as statins or renin-angiotensin inhibitors. More conclusive data are expected from ongoing trials directly exploring the role of specific cytokines antagonists. © 2013 Springer Science+Business Media New York

Potential therapeutic role of microRNAs in ischemic heart disease

Cardiovascular disease (CVD) is the most important cause of death and illness in the western world. Atherosclerosis constitutes the single most important contributor to CVD. miRNAs are small ribonucleic acids (RNAs) that negatively regulate gene expression on the post-transcriptional level by inhibiting mRNA translation or promoting mRNA degradation. Several studies demonstrated that miRNAs dysregulation have a key role in the disease process and, focusing on atherosclerotic disease, in every step of plaque formation and destabilization. These data suggest a possible therapeutic application of miRNA modulation, in particular dysregulated miRNAs can be modulated in disease process antagonizing miRNAs up-regulated and increasing miRNAs down-regulated. In this review we summarize the miRNA therapeutic techniques (antimiR, mimics, sponges, masking, and erasers) underlining their therapeutic advantages and evaluating their risks and challenges. In particular, the use of miRNA modulators as a therapeutic approach opens a novel and fascinating area of intervention in the therapy of ischemic heart disease. © 2013 Japanese College of Cardiology

Has atorvastatin more than a DUAAL face?

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Between Death and Hope After Out-of-Hospital Cardiac Arrest: Should We Rely on Biomarkers?

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Inflammatory markers in ST-elevation acute myocardial infarction

After acute myocardial infarction, ventricular remodeling is characterized by changes at the molecular, structural, geometrical and functional level that determine progression to heart failure. Inflammation plays a key role in wound healing and scar formation, affecting ventricular remodeling. Several, rather different, components of the inflammatory response were studied as biomarkers in ST-elevation acute myocardial infarction. Widely available and inexpensive tests, such as leukocyte count at admission, as well as more sophisticated immunoassays provide powerful predictors of adverse outcome in patients with ST-elevation acute myocardial infarction. We review the value of inflammatory markers in ST-elevation acute myocardial infarction and their association with ventricular remodeling, heart failure and sudden death. In conclusion, the use of these biomarkers may identify subjects at greater risk of adverse events and perhaps provide an insight into the mechanisms of disease progression

Microparticles and microRNAs: new players in the complex field of coagulation

Atherosclerosis is a complex process that begins with endothelial dysfunction, and continues with several inflammatory processes leading, eventually, to plaque rupture and formation of arterial thrombus. Increased platelet reactivity and classical coagulation pathways are not the only players of the whole thrombotic process: microparticles (MPs), irregularly shaped small vesicles released from the plasma membrane after cell activation, apoptosis, or exposure to shear stress have been demonstrated to be involved in such a process. MicroRNAs (MiRs), small-non-coding single-strand RNAs acting as post-transcriptional modulator of target gene expression are expressed in the large majority of eukaryotes. MiRs are implicated in several phenomena: control of metabolism, control of cell-differentiation, control of cell-proliferation and control of cell-apoptosis, therefore contributing to physiologic and pathogenic processes in hematologic, genetic, infective and cardiac diseases. Microparticles operate as a delivery system of MiRs, playing an active and important role in processes such as coagulation and thrombosis. These novel findings also suggest MPs and, in particular MIRs, as possible and promising therapeutic targets