Portrayal of NLRP3 Inflammasome in Atherosclerosis: Current Knowledge and Therapeutic Targets.

We are witnessing the globalization of a specific type of arteriosclerosis with rising prevalence, incidence and an overall cardiovascular disease burden. Currently, atherosclerosis increasingly affects the younger generation as compared to previous decades. While early preventive medicine has seen improvements, research advances in laboratory and clinical investigation promise to provide us with novel diagnosis tools. Given the physio-pathological complexity and epigenetic patterns of atherosclerosis and the discovery of new molecules involved, the therapeutic field of atherosclerosis has room for substantial growth. Thus, the scientific community is currently investigating the role of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a crucial component of the innate immune system in different inflammatory disorders. NLRP3 is activated by distinct factors and numerous cellular and molecular events which trigger NLRP3 inflammasome assembly with subsequent cleavage of pro-interleukin (IL)-1ß and pro-IL-18 pathways via caspase-1 activation, eliciting endothelial dysfunction, promotion of oxidative stress and the inflammation process of atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation and its role in atherosclerosis. We also emphasize its promising therapeutic pharmaceutical potential.

Multimodality imaging approach of patent foramen ovale: Practical considerations for transient ischemic attack/stroke.

A patent foramen ovale, which is present in up to 25% of the population, is a risk factor for cryptogenic stroke (which accounts for 15%-40% of strokes) and transient ischemic attack via paradoxical embolism. This narrative review focuses on the multimodality imaging approach of the diagnosis and periprocedural guidance of patent foramen ovale, with an emphasis on the use of agitated saline as contrast medium in echocardiography, starting from embryologic aspects. Therefore, we aimed to make a concise and complete presentation of the protocol used for this type of evaluation, along with multimodality imaging approach of the patent foramen ovale and practical considerations for transient ischemic attack/stroke.

MicroRNAs (miRNAs) in Cardiovascular Complications of Rheumatoid Arthritis (RA): What Is New?

Rheumatoid Arthritis (RA) is among the most prevalent and impactful rheumatologic chronic autoimmune diseases (AIDs) worldwide. Within a framework that recognizes both immunological activation and inflammatory pathways, the exact cause of RA remains unclear. It seems however, that RA is initiated by a combination between genetic susceptibility, and environmental triggers, which result in an auto-perpetuating process. The subsequently, systemic inflammation associated with RA is linked with a variety of extra-articular comorbidities, including cardiovascular disease (CVD), resulting in increased mortality and morbidity. Hitherto, vast evidence demonstrated the key role of non-coding RNAs such as microRNAs (miRNAs) in RA, and in RA-CVD related complications. In this descriptive review, we aim to highlight the specific role of miRNAs in autoimmune processes, explicitly on their regulatory roles in the pathogenesis of RA, and its CV consequences, their main role as novel biomarkers, and their possible role as therapeutic targets.

Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

The RAAS Axis and SARS-CoV-2: From Oral to Systemic Manifestations.

One of the essential regulators of arterial blood pressure, the renin-angiotensin-aldosterone system (RAAS) seems to be one of the most complex mechanisms in the human body. Since the discovery of its key components and their actions, new substances and functions are still being unraveled. The main pathway begins with the secretion of renin in the kidney and culminates with the synthesis of angiotensin II (Ang II)-a strong vasoconstrictor-thanks to the angiotensin-converting enzyme (ACE). Research conducted in 2000 identified another enzyme, named ACE2, that converts Ang II into Ang-(1-7), a heptapeptide with opposing effects to those of Ang II: vasodilation and anti-inflammatory properties. This particular enzyme became of paramount importance during the last two decades, as a result of the confrontation of the human race with life-threatening epidemics. Multiple studies have been performed in order to uncover the link between ACE2 and human coronaviruses, the results of which we systemized in order to create an overview of the pathogenic mechanism. Human coronaviruses, such as SARS-CoV and SARS-CoV-2, attach to ACE2 via their spike proteins (S), causing the destruction of the enzyme. Because ACE2 limits the production of Ang II (by converting it into Ang-(1-7)), its destruction leads to a dysregulated inflammatory response. The purpose of this review is to decipher the complex pathophysiological mechanisms underlying the multiorgan complications (oral, cardiac, pulmonary, systemic) that appear as a result of the interaction of the SARS CoV-2 virus with the angiotensin-converting enzyme type 2.

The Pulmonary Venous Return from Normal to Pathological-Clinical Correlations and Review of Literature.

Pulmonary veins carry oxygenated blood from lungs to the left atrium of the heart. The anatomy of the pulmonary veins is variable with some anatomic variants. In clinical practice the difference between the normal anatomy of pulmonary veins with its variants and abnormal anatomy is very important for clinicians. Variants of pulmonary veins may occur in number, diameter and normal venous return. We present a case report and a review of the literature with the pulmonary venous return that deviates from the usual anatomical configuration and ranges from normal variant drainage to anomalous pulmonary-systemic communication. Initially, it was considered as an anatomical variant of the pulmonary venous return associated with the persistence of the left superior vena cava. Upon detailed exploration it was established that it was an anomaly of the pulmonary venous return which led in time to the installation of its complications. Diagnosis can be difficult, sometimes missed, or only made late in adulthood when complications were installed. Knowledge of variant anatomy and anomalous pulmonary venous return play a crucial role in the diagnostically challenging patient.

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options.

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor ß (THR-ß) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

Natriuretic Peptides in Heart Failure with Preserved Left Ventricular Ejection Fraction: From Molecular Evidences to Clinical Implications.

The incidence of heart failure with preserved ejection fraction (HFpEF) is increasing and its challenging diagnosis and management combines clinical, imagistic and biological data. Natriuretic peptides (NPs) are hormones secreted in response to myocardial stretch that, by increasing cyclic guanosine monophosphate (cGMP), counteract myocardial fibrosis and hypertrophy, increase natriuresis and determine vasodilatation. While their role in HFpEF is controversial, most authors focused on b-type natriuretic peptides (BNPs) and agreed that patients may show lower levels. In this setting, newer molecules with an increased specificity, such as middle-region pro-atrial natriuretic peptide (MR-proANP), emerged as promising markers. Augmenting NP levels, either by NP analogs or breakdown inhibition, could offer a new therapeutic target in HFpEF (already approved in their reduced EF counterparts) by increasing the deficient cGMP levels found in patients. Importantly, these peptides also retain their prognostic value. This narrative review focuses on NPs' physiology, diagnosis, therapeutic and prognostic implication in HFpEF.

The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity.

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

The Prognostic Role of the Neutrophil-to-Lymphocytes Ratio in the Most Frequent Cardiovascular Diseases: An Update.

Given the continuous changes in the world, with an increasing trend of unhealthy lifestyles, metabolic comorbidities, and increased susceptibility to cardiovascular diseases (CVDs), researchers change their attention to improve not only the therapeutic platform but also current CVD predictive and prognostic tools to improve disease outcomes. As CVD is characterized by an inflammatory paradigm involving, to some degree, the innate and adaptative immune systems, the neutrophil-to-lymphocyte ratio (NLR) emerged as a potential low-cost, rapidly available, and reliable inflammatory marker, with substantial recent evidence showing its potential utility in clinical practice. Thus, in this literature review, we will present an up-to-date discussion of the prognostic role of NLR in the most frequent CVDs, such as acute and chronic coronary disease, atherosclerotic disease, heart failure, cardiac valvopathies, and cardiac arrhythmias with predilection to atrial fibrillation.

Optimizing Anticoagulation in Valvular Heart Disease: Navigating NOACs and VKAs.

BACKGROUND/OBJECTIVES: Non-vitamin K antagonist oral anticoagulants (NOACs) have demonstrated similar effectiveness and safety profiles to vitamin K antagonists (VKAs) in treating nonvalvular atrial fibrillation (AF). Given their favorable pharmacological profile, including the rapid onset and offset of action, fixed dosing, and predictable pharmacokinetics with a consistent dose-response relationship, reducing the need for frequent blood tests, researchers have investigated the potential of NOACs in patients with AF and valvular heart disease (VHD). METHODS: Clinical trials, excluding patients with mechanical prosthetic valves or moderate/severe mitral stenosis, have shown the benefits of NOACs over VKAs in this population. However, there is a need for further research to determine if these findings apply to mechanical valve prostheses and NOACs. RESULTS: Several ongoing randomized controlled trials are underway to provide more definitive evidence regarding NOAC treatment in moderate to severe rheumatic mitral stenosis. Importantly, recent trials that included patients with atrial fibrillation and bioprosthetic valves (also transcatheter heart valves) have provided evidence supporting the safety of NOACs in this specific patient population. Ongoing research aims to clearly define the specific scenarios where NOACs can be safely and effectively prescribed for various types of VHD, including moderate/severe mitral stenosis and mechanical valves. CONCLUSIONS: The aim of this review is to accurately identify the specific situations in which NOACs can be prescribed in patients with VHD, with a focus centered on each type of valvulopathy.

Multimodality Imaging in Right Heart Tumors: Proposed Algorithm towards an Appropriate Diagnosis.

A right heart tumor can be identified by transthoracic echocardiography during a routine examination or due to cardiac symptoms. The first step is the assessment by echocardiography, with its multiple techniques, and the obtained information must be judged in a clinical and biological context. The second step comprises one, sometimes even two, of the more complex modality imaging methods. The choice is driven not only by the advantages of each imaging technique but also by local expertise or the preferred imaging modality in the center. This step is followed by staging, follow-up, and/or imaging-guided excision or biopsy, which is performed in selected cases in order to obtain anatomopathological confirmation. In the presence of features suggestive of malignancy or causing hemodynamic impairment, a transvenous biopsy is essential before the more complex imaging modalities (which are still relevant in the staging process). Using a structured imaging approach, it is possible to reach an appropriate diagnosis without a biopsy. Frequently, these imaging techniques have a complementary role, so an integrated imaging approach is recommended. This proposed algorithm for appropriate diagnosis of right heart tumors could serve as a practical guide for clinicians (not only imaging specialists).